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Ramos da Silva J, Bitencourt Rodrigues K, Formoso Pelegrin G, Silva Sales N, Muramatsu H, de Oliveira Silva M, Porchia BFMM, Moreno ACR, Aps LRMM, Venceslau-Carvalho AA, Tombácz I, Fotoran WL, Karikó K, Lin PJC, Tam YK, de Oliveira Diniz M, Pardi N*, de Souza Ferreira LC.

Single immunizations of self-amplifying or non-replicating mRNA-LNP vaccines control HPV-associated tumors in mice.

Sci Transl Med. 2023 Mar 3:eabn3464.

doi: 10.1126/scitranslmed.abn3464.; PMID: 36867683.

As mRNA vaccines have proved to be very successful in battling the coronavirus disease 2019 (COVID-19) pandemic, this new modality has attracted widespread interest for the development of potent vaccines against other infectious diseases and cancer. Cervical cancer caused by persistent human papillomavirus (HPV) infection is a major cause of cancer-related deaths in women, and the development of safe and effective therapeutic strategies is urgently needed. In the present study, we compared the performance of three different mRNA vaccine modalities to target tumors associated with HPV-16 infection in mice. We generated lipid nanoparticle (LNP)-encapsulated self-amplifying mRNA as well as unmodified and nucleoside-modified non-replicating mRNA vaccines encoding a chimeric protein derived from the fusion of the HPV-16 E7 oncoprotein and the herpes simplex virus type 1 glycoprotein D (gDE7). We demonstrated that single low-dose immunizations with any of the three gDE7 mRNA vaccines induced activation of E7-specific CD8+ T cells, generated memory T cell responses capable of preventing tumor relapses, and eradicated subcutaneous tumors at different growth stages. In addition, the gDE7 mRNA-LNP vaccines induced potent tumor protection in two different orthotopic mouse tumor models after administration of a single vaccine dose. Last, comparative studies demonstrated that all three gDE7 mRNA-LNP vaccines proved to be superior to gDE7 DNA and gDE7 recombinant protein vaccines. Collectively, we demonstrated the immunogenicity and therapeutic efficacy of three different mRNA vaccines in extensive comparative experiments. Our data support further evaluation of these mRNA vaccines in clinical trials.

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Amanat F, Clark J, Carreño JM, Strohmeier S, Yellin T, Meade PS, Bhavsar D, Muramatsu H, Sun W, Coughlan L, Pardi N, Krammer F.

Immunity to Seasonal Coronavirus Spike Proteins Does Not Protect from SARS-CoV-2 Challenge in a Mouse Model but Has No Detrimental Effect on Protection Mediated by COVID-19 mRNA Vaccination.

J Virol. 2023 Feb 13:e0166422.

doi: 10.1128/jvi.01664-22; PMID: 36779758.

Seasonal coronaviruses have been circulating widely in the human population for many years. With increasing age, humans are more likely to have been exposed to these viruses and to have developed immunity against them. It has been hypothesized that this immunity to seasonal coronaviruses may provide partial protection against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and it has also been shown that coronavirus disease 2019 (COVID-19) vaccination induces a back-boosting effects against the spike proteins of seasonal betacoronaviruses. In this study, we tested if immunity to the seasonal coronavirus spikes from OC43, HKU1, 229E, or NL63 would confer protection against SARS-CoV-2 challenge in a mouse model, and whether pre-existing immunity against these spikes would weaken the protection afforded by mRNA COVID-19 vaccination. We found that mice vaccinated with the seasonal coronavirus spike proteins had no increased protection compared to the negative controls. While a negligible back-boosting effect against betacoronavirus spike proteins was observed after SARS-CoV-2 infection, there was no negative original antigenic sin-like effect on the immune response and protection induced by SARS-CoV-2 mRNA vaccination in animals with pre-existing immunity to seasonal coronavirus spike proteins.

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Schiepers A, van 't Wout MFL, Greaney AJ, Zang T, Muramatsu H, Lin PJC, Tam YK, Mesin L, Starr TN, Bieniasz PD, Pardi N, Bloom JD, Victora GD.

Molecular fate-mapping of serum antibody responses to repeat immunization.

Nature. 2023 Jan 16.

doi: 10.1038/s41586-023-05715-3; PMID: 36646114.

The protective efficacy of serum antibody results from the interplay of antigen-specific B cell clones of different affinities and specificities. These cellular dynamics underlie serum-level phenomena such as “Original Antigenic Sin” (OAS), a proposed propensity of the immune system to rely repeatedly on the first cohort of B cells engaged by an antigenic stimulus when encountering related antigens, in detriment of inducing de novo responses1-5. OAS-type suppression of new, variant-specific antibodies may pose a barrier to vaccination against rapidly evolving viruses such as influenza and SARS-CoV-26,7. Precise measurement of OAS-type suppression is challenging because cellular and temporal origins cannot readily be ascribed to antibodies in circulation; thus, its impact on subsequent antibody responses remains unclear5,8. Here, we introduce a molecular fate-mapping approach in which serum antibodies derived from specific cohorts of B cells can be differentially detected. We show that serum responses to sequential homologous boosting derive overwhelmingly from primary cohort B cells, while later induction of new antibody responses from naïve B cells is strongly suppressed. Such “primary addiction” decreases sharply as a function of antigenic distance, allowing reimmunization with divergent viral glycoproteins to produce de novo antibody responses targeting epitopes absent from the priming variant. Our findings have implications for the understanding of OAS and for the design and testing of vaccines against evolving pathogens.

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van de Ven K, Lanfermeijer J, van Dijken H, Muramatsu H, Vilas Boas de Melo C, Lenz S, Peters F, Beattie MB, Lin PJC, Ferreira JA, van den Brand J, van Baarle D, Pardi N*, de Jonge J.

A universal influenza mRNA vaccine candidate boosts T cell responses and reduces zoonotic influenza virus disease in ferrets.

Sci Adv. 2022 Dec 14;8(50):eadc9937.

doi: 10.1126/sciadv.adc9937; PMID: 36516261.

Universal influenza vaccines should protect against continuously evolving and newly emerging influenza viruses. T cells may be an essential target of such vaccines, as they can clear infected cells through recognition of conserved influenza virus epitopes. We evaluated a novel T cell–inducing nucleoside-modified messenger RNA (mRNA) vaccine that encodes the conserved nucleoprotein, matrix protein 1, and polymerase basic protein 1 of an H1N1 influenza virus. To mimic the human situation, we applied the mRNA vaccine as a prime-boost regimen in naïve ferrets (mimicking young children) and as a booster in influenza-experienced ferrets (mimicking adults). The vaccine induced and boosted broadly reactive T cells in the circulation, bone marrow, and respiratory tract. Booster vaccination enhanced protection against heterosubtypic infection with a potential pandemic H7N9 influenza virus in influenza-experienced ferrets. Our findings show that mRNA vaccines encoding internal influenza virus proteins represent a promising strategy to induce broadly protective T cell immunity against influenza viruses.

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Arevalo CP, Bolton MJ, Le Sage V, Ye N, Furey C, Muramatsu H, Alameh MG, Pardi N, Drapeau EM, Parkhouse K, Garretson T, Morris JS, Moncla LH, Tam YK, Fan SHY, Lakdawala SS, Weissman D, Hensley SE.

A multivalent nucleoside-modified mRNA vaccine against all known influenza virus subtypes.

Science. 2022 Nov 25;378(6622):899-904.

doi: 10.1126/science.abm0271; PMID: 36423275.

Seasonal influenza vaccines offer little protection against pandemic influenza virus strains. It is difficult to create effective prepandemic vaccines because it is uncertain which influenza virus subtype will cause the next pandemic. In this work, we developed a nucleoside-modified messenger RNA (mRNA)–lipid nanoparticle vaccine encoding hemagglutinin antigens from all 20 known influenza A virus subtypes and influenza B virus lineages. This multivalent vaccine elicited high levels of cross-reactive and subtype-specific antibodies in mice and ferrets that reacted to all 20 encoded antigens. Vaccination protected mice and ferrets challenged with matched and mismatched viral strains, and this protection was at least partially dependent on antibodies. Our studies indicate that mRNA vaccines can provide protection against antigenically variable viruses by simultaneously inducing antibodies against multiple antigens.

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McMahon M, O'Dell G, Tan J, Sárközy A, Vadovics M, Carreño JM, Puente-Massaguer E, Muramatsu H, Bajusz C, Rijnink W, Beattie M, Tam YK, Kirkpatrick Roubidoux E, Francisco I, Strohmeier S, Kanekiyo M, Graham BS, Krammer F, Pardi N.*

Assessment of a quadrivalent nucleoside-modified mRNA vaccine that protects against group 2 influenza viruses.

Proc Natl Acad Sci U S A. 2022 Nov 8;119(45):e2206333119.

doi: 10.1073/pnas.2206333119; PMID: 36322769.

Combined vaccine formulations targeting not only hemagglutinin but also other influenza virus antigens could form the basis for a universal influenza virus vaccine that has the potential to elicit long-lasting, broadly cross-reactive immune responses. Lipid nanoparticle (LNP)-encapsulated messenger RNA (mRNA) vaccines can be utilized to efficiently target multiple antigens with a single vaccine. Here, we assessed the immunogenicity and protective efficacy of nucleoside-modified mRNA-LNP vaccines that contain four influenza A group 2 virus antigens (hemagglutinin stalk, neuraminidase, matrix protein 2, and nucleoprotein) in mice. We found that all vaccine components induced antigen-specific cellular and humoral immune responses after administration of a single dose. While the monovalent formulations were not exclusively protective, the combined quadrivalent formulation protected mice from all challenge viruses, including a relevant H1N1 influenza virus group 1 strain, with minimal weight loss. Importantly, the combined vaccine protected from morbidity at a dose of 125 ng per antigen after a single vaccination in mice. With these findings, we confidently conclude that the nucleoside-modified mRNA-LNP platform can be used to elicit protection against a large panel of influenza viruses.

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Pardi N*, Carreño JM, O'Dell G, Tan J, Bajusz C, Muramatsu H, Rijnink W, Strohmeier S, Loganathan M, Bielak D, Sung MMH, Tam YK, Krammer F, McMahon M.

Development of a pentavalent broadly protective nucleoside-modified mRNA vaccine against influenza B viruses.

Nat Commun. 2022 Aug 9;13(1):4677.

doi: 10.1038/s41467-022-32149-8; PMID: 35945226; PMCID: PMC9362976.

Messenger RNA (mRNA) vaccines represent a new, effective vaccine platform with high capacity for rapid development. Generation of a universal influenza virus vaccine with the potential to elicit long-lasting, broadly cross-reactive immune responses is a necessity for reducing influenza-associated morbidity and mortality. Here we focus on the development of a universal influenza B virus vaccine based on the lipid nanoparticle-encapsulated nucleoside-modified mRNA (mRNA-LNP) platform. We evaluate vaccine candidates based on different target antigens that afford protection against challenge with ancestral and recent influenza B viruses from both antigenic lineages. A pentavalent vaccine combining all tested antigens protects mice from morbidity at a very low dose of 50 ng per antigen after a single vaccination. These findings support the further advancement of nucleoside-modified mRNA-LNPs expressing multiple conserved antigens as universal influenza virus vaccine candidates.

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Muramatsu H, Lam K, Bajusz C, Laczkó D, Karikó K, Schreiner P, Martin A, Lutwyche P, Heyes J, Pardi N.*

Lyophilization provides long-term stability for a lipid nanoparticle-formulated, nucleoside-modified mRNA vaccine.

Mol Ther. 2022 May 4;30(5):1941-1951.

doi: 10.1016/j.ymthe.2022.02.001; PMID: 35131437; PMCID: PMC8815268.

Lipid nanoparticle (LNP)-formulated nucleoside-modified mRNA vaccines have proven to be very successful in the fight against the coronavirus disease 2019 (COVID-19) pandemic. They are effective, safe, and can be produced in large quantities. However, the long-term storage of mRNA-LNP vaccines without freezing is still a challenge. Here, we demonstrate that nucleoside-modified mRNA-LNPs can be lyophilized, and the physicochemical properties of the lyophilized material do not significantly change for 12 weeks after storage at room temperature and for at least 24 weeks after storage at 4°C. Importantly, we show in comparative mouse studies that lyophilized firefly luciferase-encoding mRNA-LNPs maintain their high expression, and no decrease in the immunogenicity of a lyophilized influenza virus hemagglutinin-encoding mRNA-LNP vaccine was observed after 12 weeks of storage at room temperature or for at least 24 weeks after storage at 4°C. Our studies offer a potential solution to overcome the long-term storage-related limitations of nucleoside-modified mRNA-LNP vaccines.

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Alameh MG, Tombácz I, Bettini E, Lederer K, Sittplangkoon C, Wilmore JR, Gaudette BT, Soliman OY, Pine M, Hicks P, Manzoni TB, Knox JJ, Johnson JL, Laczkó D, Muramatsu H, Davis B, Meng W, Rosenfeld AM, Strohmeier S, Lin PJC, Mui BL, Tam YK, Karikó K, Jacquet A, Krammer F, Bates P, Cancro MP, Weissman D, Luning Prak ET, Allman D, Locci M, Pardi N.*

Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses.

Immunity. 2021 Dec 14;54(12):2877-2892.e7.

doi: 10.1016/j.immuni.2021.11.001;  PMID: 34852217; PMCID: PMC8566475.

Adjuvants are critical for improving the quality and magnitude of adaptive immune responses to vaccination. Lipid nanoparticle (LNP)-encapsulated nucleoside-modified mRNA vaccines have shown great efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the mechanism of action of this vaccine platform is not well-characterized. Using influenza virus and SARS-CoV-2 mRNA and protein subunit vaccines, we demonstrated that our LNP formulation has intrinsic adjuvant activity that promotes induction of strong T follicular helper cell, germinal center B cell, long-lived plasma cell, and memory B cell responses that are associated with durable and protective antibodies in mice. Comparative experiments demonstrated that this LNP formulation outperformed a widely used MF59-like adjuvant, AddaVax. The adjuvant activity of the LNP relies on the ionizable lipid component and on IL-6 cytokine induction but not on MyD88- or MAVS-dependent sensing of LNPs. Our study identified LNPs as a versatile adjuvant that enhances the efficacy of traditional and next-generation vaccine platforms.

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Hogan MJ, Pardi N.*

mRNA Vaccines in the COVID-19 Pandemic and Beyond.

Annu Rev Med. 2022 Jan 27;73:17-39.

doi: 10.1146/annurev-med-042420-112725; PMID: 34669432.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. This extraordinary situation prompted entities in government, industry, and academia to work together at unprecedented speed to develop safe and effective vaccines. Indeed, vaccines of multiple types have been generated in record time, and many have been evaluated in clinical trials. Of these, messenger RNA (mRNA) vaccines have emerged as lead candidates due to their speed of development and high degree of safety and efficacy. To date, two mRNA vaccines have received approval for human use, providing proof of the feasibility of this next-generation vaccine modality. This review gives a detailed overview about the types of mRNA vaccines developed for SARS-CoV-2, discusses and compares preclinical and clinical data, gives a mechanistic overview about immune responses generated by mRNA vaccination, and speculates on the challenges and promising future of this emergent vaccine platform

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Freyn AW, Pine M, Rosado VC, Benz M, Muramatsu H, Beattie M, Tam YK, Krammer F, Palese P, Nachbagauer R, McMahon M, Pardi N.*

Antigen modifications improve nucleoside-modified mRNA-based influenza virus vaccines in mice.

Mol Ther Methods Clin Dev. 2021 Jun 12;22:84-95.

doi: 10.1016/j.omtm.2021.06.003; PMID: 34485597; PMCID: PMC8390451.

Nucleoside-modified, lipid nanoparticle-encapsulated mRNAs have recently emerged as suitable vaccines for influenza viruses and other pathogens in part because the platform allows delivery of multiple antigens in a single immunization. mRNA vaccines allow for easy antigen modification, enabling rapid iterative design. We studied protein modifications such as mutating functional sites, changing secretion potential, and altering protein conformation, which could improve the safety and/or potency of mRNA-based influenza virus vaccines. Mice were vaccinated intradermally with wild-type or mutant constructs of influenza virus hemagglutinin (HA), neuraminidase (NA), matrix protein 2 (M2), nucleoprotein (NP), or matrix protein 1 (M1). Membrane-bound HA constructs elicited more potent and protective antibody responses than secreted forms. Altering the catalytic site of NA to reduce enzymatic activity decreased reactogenicity while protective immunity was maintained. Disruption of M2 ion channel activity improved immunogenicity and protective efficacy. A comparison of internal proteins NP and M1 revealed the superiority of NP in conferring protection from influenza virus challenge. These findings support the use of the nucleoside-modified mRNA platform for guided antigen design for influenza virus with extension to other pathogens.

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Martinez DR, Schäfer A, Leist SR, De la Cruz G, West A, Atochina-Vasserman EN, Lindesmith LC, Pardi N, Parks R, Barr M, Li D, Yount B, Saunders KO, Weissman D, Haynes BF, Montgomery SA, Baric RS.

Chimeric spike mRNA vaccines protect against Sarbecovirus challenge in mice.

Science. 2021 Aug 27;373(6558):991-998.

doi: 10.1126/science.abi4506; PMID: 34214046; PMCID: PMC8899822.

The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 and SARS-CoV-2 in 2019 highlights the need to develop universal vaccination strategies against the broader Sarbecovirus subgenus. Using chimeric spike designs, we demonstrate protection against challenge from SARS-CoV, SARS-CoV-2, SARS-CoV-2 B.1.351, bat CoV (Bt-CoV) RsSHC014, and a heterologous Bt-CoV WIV-1 in vulnerable aged mice. Chimeric spike messenger RNAs (mRNAs) induced high levels of broadly protective neutralizing antibodies against high-risk Sarbecoviruses. By contrast, SARS-CoV-2 mRNA vaccination not only showed a marked reduction in neutralizing titers against heterologous Sarbecoviruses, but SARS-CoV and WIV-1 challenge in mice resulted in breakthrough infections. Chimeric spike mRNA vaccines efficiently neutralized D614G, mink cluster five, and the UK B.1.1.7 and South African B.1.351 variants of concern. Thus, multiplexed-chimeric spikes can prevent SARS-like zoonotic coronavirus infections with pandemic potential.

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Szőke D, Kovács G, Kemecsei É, Bálint L, Szoták-Ajtay K, Aradi P, Styevkóné Dinnyés A, Mui BL, Tam YK, Madden TD, Karikó K, Kataru RP, Hope MJ, Weissman D, Mehrara BJ, Pardi N*, Jakus Z.

Nucleoside-modified VEGFC mRNA induces organ-specific lymphatic growth and reverses experimental lymphedema.

Nat Commun. 2021 Jun 8;12(1):3460.

doi: 10.1038/s41467-021-23546-6; PMID: 34103491; PMCID: PMC8187400.

Lack or dysfunction of the lymphatics leads to secondary lymphedema formation that seriously reduces the function of the affected organs and results in degradation of quality of life. Currently, there is no definitive treatment option for lymphedema. Here, we utilized nucleoside-modified mRNA encapsulated in lipid nanoparticles (LNPs) encoding murine Vascular Endothelial Growth Factor C (VEGFC) to stimulate lymphatic growth and function and reduce experimental lymphedema in mouse models. We demonstrated that administration of a single low-dose of VEGFC mRNA-LNPs induced durable, organ-specific lymphatic growth and formation of a functional lymphatic network. Importantly, VEGFC mRNA-LNP treatment reversed experimental lymphedema by restoring lymphatic function without inducing any obvious adverse events. Collectively, we present a novel application of the nucleoside-modified mRNA-LNP platform, describe a model for identifying the organ-specific physiological and pathophysiological roles of the lymphatics, and propose an efficient and safe treatment option that may serve as a novel therapeutic tool to reduce lymphedema.

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Rothgangl T, Dennis MK, Lin PJC, Oka R, Witzigmann D, Villiger L, Qi W, Hruzova M, Kissling L, Lenggenhager D, Borrelli C, Egli S, Frey N, Bakker N, Walker JA 2nd, Kadina AP, Victorov DV, Pacesa M, Kreutzer S, Kontarakis Z, Moor A, Jinek M, Weissman D, Stoffel M, van Boxtel R, Holden K, Pardi N, Thöny B, Häberle J, Tam YK, Semple SC, Schwank G.

In vivo adenine base editing of PCSK9 in macaques reduces LDL cholesterol levels.

Nat Biotechnol. 2021 Aug;39(8):949-957.

doi: 10.1038/s41587-021-00933-4; PMID: 34012094; PMCID: PMC8352781.

Most known pathogenic point mutations in humans are C•G to T•A substitutions, which can be directly repaired by adenine base editors (ABEs). In this study, we investigated the efficacy and safety of ABEs in the livers of mice and cynomolgus macaques for the reduction of blood low-density lipoprotein (LDL) levels. Lipid nanoparticle-based delivery of mRNA encoding an ABE and a single-guide RNA targeting PCSK9, a negative regulator of LDL, induced up to 67% editing (on average, 61%) in mice and up to 34% editing (on average, 26%) in macaques. Plasma PCSK9 and LDL levels were stably reduced by 95% and 58% in mice and by 32% and 14% in macaques, respectively. ABE mRNA was cleared rapidly, and no off-target mutations in genomic DNA were found. Re-dosing in macaques did not increase editing, possibly owing to the detected humoral immune response to ABE upon treatment. These findings support further investigation of ABEs to treat patients with monogenic liver diseases.

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Saunders KO, Lee E, Parks R, Martinez DR, Li D, Chen H, Edwards RJ, Gobeil S, Barr M, Mansouri K, Alam SM, Sutherland LL, Cai F, Sanzone AM, Berry M, Manne K, Bock KW, Minai M, Nagata BM, Kapingidza AB, Azoitei M, Tse LV, Scobey TD, Spreng RL, Rountree RW, DeMarco CT, Denny TN, Woods CW, Petzold EW, Tang J, Oguin TH 3rd, Sempowski GD, Gagne M, Douek DC, Tomai MA, Fox CB, Seder R, Wiehe K, Weissman D, Pardi N, Golding H, Khurana S, Acharya P, Andersen H, Lewis MG, Moore IN, Montefiori DC, Baric RS, Haynes BF.

Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses.

Nature. 2021 Jun;594(7864):553-559.

doi: 10.1038/s41586-021-03594-0; PMID: 33971664; PMCID: PMC8528238.

Betacoronaviruses caused the outbreaks of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome, as well as the current pandemic of SARS coronavirus 2 (SARS-CoV-2)1-4. Vaccines that elicit protective immunity against SARS-CoV-2 and betacoronaviruses that circulate in animals have the potential to prevent future pandemics. Here we show that the immunization of macaques with nanoparticles conjugated with the receptor-binding domain of SARS-CoV-2, and adjuvanted with 3M-052 and alum, elicits cross-neutralizing antibody responses against bat coronaviruses, SARS-CoV and SARS-CoV-2 (including the B.1.1.7, P.1 and B.1.351 variants). Vaccination of macaques with these nanoparticles resulted in a 50% inhibitory reciprocal serum dilution (ID50) neutralization titre of 47,216 (geometric mean) for SARS-CoV-2, as well as in protection against SARS-CoV-2 in the upper and lower respiratory tracts. Nucleoside-modified mRNAs that encode a stabilized transmembrane spike or monomeric receptor-binding domain also induced cross-neutralizing antibody responses against SARS-CoV and bat coronaviruses, albeit at lower titres than achieved with the nanoparticles. These results demonstrate that current mRNA-based vaccines may provide some protection from future outbreaks of zoonotic betacoronaviruses, and provide a multimeric protein platform for the further development of vaccines against multiple (or all) betacoronaviruses.

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Lederer K, Castaño D, Gómez Atria D, Oguin TH 3rd, Wang S, Manzoni TB, Muramatsu H, Hogan MJ, Amanat F, Cherubin P, Lundgreen KA, Tam YK, Fan SHY, Eisenlohr LC, Maillard I, Weissman D, Bates P, Krammer F, Sempowski GD, Pardi N, Locci M.

SARS-CoV-2 mRNA Vaccines Foster Potent Antigen-Specific Germinal Center Responses Associated with Neutralizing Antibody Generation.

Immunity. 2020 Dec 15;53(6):1281-1295.e5.

doi: 10.1016/j.immuni.2020.11.009; PMID: 33296685; PMCID: PMC7680029.

The deployment of effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical to eradicate the coronavirus disease 2019 (COVID-19) pandemic. Many licensed vaccines confer protection by inducing long-lived plasma cells (LLPCs) and memory B cells (MBCs), cell types canonically generated during germinal center (GC) reactions. Here, we directly compared two vaccine platforms-mRNA vaccines and a recombinant protein formulated with an MF59-like adjuvant-looking for their abilities to quantitatively and qualitatively shape SARS-CoV-2-specific primary GC responses over time. We demonstrated that a single immunization with SARS-CoV-2 mRNA, but not with the recombinant protein vaccine, elicited potent SARS-CoV-2-specific GC B and T follicular helper (Tfh) cell responses as well as LLPCs and MBCs. Importantly, GC responses strongly correlated with neutralizing antibody production. mRNA vaccines more efficiently induced key regulators of the Tfh cell program and influenced the functional properties of Tfh cells. Overall, this study identifies SARS-CoV-2 mRNA vaccines as strong candidates for promoting robust GC-derived immune responses.

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Pardi N*, Weissman D.

Development of vaccines and antivirals for combating viral pandemics.

Nat Biomed Eng. 2020 Dec;4(12):1128-1133.

doi: 10.1038/s41551-020-00658-w. PMID: 33293724; PMCID: PMC8336060.

Proactive efforts towards the development of new vaccines and antivirals, and the elimination of bottlenecks in vaccine development, will be essential to containing and eradicating future pandemics.

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Laczkó D, Hogan MJ, Toulmin SA, Hicks P, Lederer K, Gaudette BT, Castaño D, Amanat F, Muramatsu H, Oguin TH 3rd, Ojha A, Zhang L, Mu Z, Parks R, Manzoni TB, Roper B, Strohmeier S, Tombácz I, Arwood L, Nachbagauer R, Karikó K, Greenhouse J, Pessaint L, Porto M, Putman-Taylor T, Strasbaugh A, Campbell TA, Lin PJC, Tam YK, Sempowski GD, Farzan M, Choe H, Saunders KO, Haynes BF, Andersen H, Eisenlohr LC, Weissman D, Krammer F, Bates P, Allman D, Locci M, Pardi N.*

A Single Immunization with Nucleoside-Modified mRNA Vaccines Elicits Strong Cellular and Humoral Immune Responses against SARS-CoV-2 in Mice.

Immunity. 2020 Oct 13;53(4):724-732.e7.

doi: 10.1016/j.immuni.2020.07.019; PMID: 32783919; PMCID: PMC7392193.

SARS-CoV-2 infection has emerged as a serious global pandemic. Because of the high transmissibility of the virus and the high rate of morbidity and mortality associated with COVID-19, developing effective and safe vaccines is a top research priority. Here, we provide a detailed evaluation of the immunogenicity of lipid nanoparticle-encapsulated, nucleoside-modified mRNA (mRNA-LNP) vaccines encoding the full-length SARS-CoV-2 spike protein or the spike receptor binding domain in mice. We demonstrate that a single dose of these vaccines induces strong type 1 CD4+ and CD8+ T cell responses, as well as long-lived plasma and memory B cell responses. Additionally, we detect robust and sustained neutralizing antibody responses and the antibodies elicited by nucleoside-modified mRNA vaccines do not show antibody-dependent enhancement of infection in vitro. Our findings suggest that the nucleoside-modified mRNA-LNP vaccine platform can induce robust immune responses and is a promising candidate to combat COVID-19.

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Raj DK, Das Mohapatra A, Jnawali A, Zuromski J, Jha A, Cham-Kpu G, Sherman B, Rudlaff RM, Nixon CE, Hilton N, Oleinikov AV, Chesnokov O, Merritt J, Pond-Tor S, Burns L, Jolly G, Ben Mamoun C, Kabyemela E, Muehlenbachs A, Lambert L, Orr-Gonzalez S, Gnädig NF, Fidock DA, Park S, Dvorin JD, Pardi N, Weissman D, Mui BL, Tam YK, Friedman JF, Fried M, Duffy PE, Kurtis JD.

Anti-PfGARP activates programmed cell death of parasites and reduces severe malaria.

Nature. 2020 Jun;582(7810):104-108.

doi: 10.1038/s41586-020-2220-1; PMID: 32427965; PMCID: PMC7372601.

Malaria caused by Plasmodium falciparum remains the leading single-agent cause of mortality in children1, yet the promise of an effective vaccine has not been fulfilled. Here, using our previously described differential screening method to analyse the proteome of blood-stage P. falciparum parasites2, we identify P. falciparum glutamic-acid-rich protein (PfGARP) as a parasite antigen that is recognized by antibodies in the plasma of children who are relatively resistant-but not those who are susceptible-to malaria caused by P. falciparum. PfGARP is a parasite antigen of 80 kDa that is expressed on the exofacial surface of erythrocytes infected by early-to-late-trophozoite-stage parasites. We demonstrate that antibodies against PfGARP kill trophozoite-infected erythrocytes in culture by inducing programmed cell death in the parasites, and that vaccinating non-human primates with PfGARP partially protects against a challenge with P. falciparum. Furthermore, our longitudinal cohort studies showed that, compared to individuals who had naturally occurring anti-PfGARP antibodies, Tanzanian children without anti-PfGARP antibodies had a 2.5-fold-higher risk of severe malaria and Kenyan adolescents and adults without these antibodies had a twofold-higher parasite density. By killing trophozoite-infected erythrocytes, PfGARP could synergize with other vaccines that target parasite invasion of hepatocytes or the invasion of and egress from erythrocytes.

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Freyn AW, Ramos da Silva J, Rosado VC, Bliss CM, Pine M, Mui BL, Tam YK, Madden TD, de Souza Ferreira LC, Weissman D, Krammer F, Coughlan L, Palese P, Pardi N*, Nachbagauer R.

A Multi-Targeting, Nucleoside-Modified mRNA Influenza Virus Vaccine Provides Broad Protection in Mice.

Mol Ther. 2020 Jul 8;28(7):1569-1584.

doi: 10.1016/j.ymthe.2020.04.018; PMID: 32359470; PMCID: PMC7335735.

Influenza viruses are respiratory pathogens of public health concern worldwide with up to 650,000 deaths occurring each year. Seasonal influenza virus vaccines are employed to prevent disease, but with limited effectiveness. Development of a universal influenza virus vaccine with the potential to elicit long-lasting, broadly cross-reactive immune responses is necessary for reducing influenza virus prevalence. In this study, we have utilized lipid nanoparticle-encapsulated, nucleoside-modified mRNA vaccines to intradermally deliver a combination of conserved influenza virus antigens (hemagglutinin stalk, neuraminidase, matrix-2 ion channel, and nucleoprotein) and induce strong immune responses with substantial breadth and potency in a murine model. The immunity conferred by nucleoside-modified mRNA-lipid nanoparticle vaccines provided protection from challenge with pandemic H1N1 virus at 500 times the median lethal dose after administration of a single immunization, and the combination vaccine protected from morbidity at a dose of 50 ng per antigen. The broad protective potential of a single dose of combination vaccine was confirmed by challenge with a panel of group 1 influenza A viruses. These findings support the advancement of nucleoside-modified mRNA-lipid nanoparticle vaccines expressing multiple conserved antigens as universal influenza virus vaccine candidates.

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Pardi N*, Hogan MJ, Weissman D.

Recent advances in mRNA vaccine technology.

Curr Opin Immunol. 2020 Aug;65:14-20.

doi: 10.1016/j.coi.2020.01.008; PMID: 32244193.

Messenger RNA (mRNA) vaccines represent a relatively new vaccine class showing great promise for the future. This optimism is built on recently published studies demonstrating the efficacy of mRNA vaccines in combatting several types of cancer and infectious pathogens where conventional vaccine platforms may fail to induce protective immune responses. These results would not have been possible without critical recent innovations in the field, such as the development of safe and efficient materials for in vivo mRNA delivery and advanced protocols for the production of high quality mRNA. This review summarizes the most important developments in mRNA vaccines from the past few years and discusses the challenges and future directions for the field.

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Pardi N*, LaBranche CC, Ferrari G, Cain DW, Tombácz I, Parks RJ, Muramatsu H, Mui BL, Tam YK, Karikó K, Polacino P, Barbosa CJ, Madden TD, Hope MJ, Haynes BF, Montefiori DC, Hu SL, Weissman D.

Characterization of HIV-1 Nucleoside-Modified mRNA Vaccines in Rabbits and Rhesus Macaques.

Mol Ther Nucleic Acids. 2019 Apr 15;15:36-47.

doi: 10.1016/j.omtn.2019.03.003; PMID: 30974332; PMCID: PMC6454128.

Despite the enormous effort in the development of effective vaccines against HIV-1, no vaccine candidate has elicited broadly neutralizing antibodies in humans. Thus, generation of more effective anti-HIV vaccines is critically needed. Here we characterize the immune responses induced by nucleoside-modified and purified mRNA-lipid nanoparticle (mRNA-LNP) vaccines encoding the clade C transmitted/founder HIV-1 envelope (Env) 1086C. Intradermal vaccination with nucleoside-modified 1086C Env mRNA-LNPs elicited high levels of gp120-specific antibodies in rabbits and rhesus macaques. Antibodies generated in rabbits neutralized a tier 1 virus, but no tier 2 neutralization activity could be measured. Importantly, three of six non-human primates developed antibodies that neutralized the autologous tier 2 strain. Despite stable anti-gp120 immunoglobulin G (IgG) levels, tier 2 neutralization titers started to drop 4 weeks after booster immunizations. Serum from both immunized rabbits and non-human primates demonstrated antibody-dependent cellular cytotoxicity activity. Collectively, these results are supportive of continued development of nucleoside-modified and purified mRNA-LNP vaccines for HIV. Optimization of Env immunogens and vaccination protocols are needed to increase antibody neutralization breadth and durability.

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Pardi N, Parkhouse K, Kirkpatrick E, McMahon M, Zost SJ, Mui BL, Tam YK, Karikó K, Barbosa CJ, Madden TD, Hope MJ, Krammer F, Hensley SE, Weissman D.

Nucleoside-modified mRNA immunization elicits influenza virus hemagglutinin stalk-specific antibodies.

Nat Commun. 2018 Aug 22;9(1):3361.

doi: 10.1038/s41467-018-05482-0; PMID: 30135514; PMCID: PMC6105651.

Currently available influenza virus vaccines have inadequate effectiveness and are reformulated annually due to viral antigenic drift. Thus, development of a vaccine that confers long-term protective immunity against antigenically distant influenza virus strains is urgently needed. The highly conserved influenza virus hemagglutinin (HA) stalk represents one of the potential targets of broadly protective/universal influenza virus vaccines. Here, we evaluate a potent broadly protective influenza virus vaccine candidate that uses nucleoside-modified and purified mRNA encoding full-length influenza virus HA formulated in lipid nanoparticles (LNPs). We demonstrate that immunization with HA mRNA-LNPs induces antibody responses against the HA stalk domain of influenza virus in mice, rabbits, and ferrets. The HA stalk-specific antibody response is associated with protection from homologous, heterologous, and heterosubtypic influenza virus infection in mice.

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Pardi N*, Hogan MJ, Naradikian MS, Parkhouse K, Cain DW, Jones L, Moody MA, Verkerke HP, Myles A, Willis E, LaBranche CC, Montefiori DC, Lobby JL, Saunders KO, Liao HX, Korber BT, Sutherland LL, Scearce RM, Hraber PT, Tombácz I, Muramatsu H, Ni H, Balikov DA, Li C, Mui BL, Tam YK, Krammer F, Karikó K, Polacino P, Eisenlohr LC, Madden TD, Hope MJ, Lewis MG, Lee KK, Hu SL, Hensley SE, Cancro MP, Haynes BF, Weissman D.

Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses.

J Exp Med. 2018 Jun 4;215(6):1571-1588.

doi: 10.1084/jem.20171450; PMID: 29739835; PMCID: PMC5987916.

T follicular helper (Tfh) cells are required to develop germinal center (GC) responses and drive immunoglobulin class switch, affinity maturation, and long-term B cell memory. In this study, we characterize a recently developed vaccine platform, nucleoside-modified, purified mRNA encapsulated in lipid nanoparticles (mRNA-LNPs), that induces high levels of Tfh and GC B cells. Intradermal vaccination with nucleoside-modified mRNA-LNPs encoding various viral surface antigens elicited polyfunctional, antigen-specific, CD4+ T cell responses and potent neutralizing antibody responses in mice and nonhuman primates. Importantly, the strong antigen-specific Tfh cell response and high numbers of GC B cells and plasma cells were associated with long-lived and high-affinity neutralizing antibodies and durable protection. Comparative studies demonstrated that nucleoside-modified mRNA-LNP vaccines outperformed adjuvanted protein and inactivated virus vaccines and pathogen infection. The incorporation of noninflammatory, modified nucleosides in the mRNA is required for the production of large amounts of antigen and for robust immune responses.

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Pardi N, Hogan MJ, Porter FW, Weissman D.

mRNA vaccines - a new era in vaccinology.

Nat Rev Drug Discov. 2018 Apr;17(4):261-279.

doi: 10.1038/nrd.2017.243; PMID: 29326426; PMCID: PMC5906799.

mRNA vaccines represent a promising alternative to conventional vaccine approaches because of their high potency, capacity for rapid development and potential for low-cost manufacture and safe administration. However, their application has until recently been restricted by the instability and inefficient in vivo delivery of mRNA. Recent technological advances have now largely overcome these issues, and multiple mRNA vaccine platforms against infectious diseases and several types of cancer have demonstrated encouraging results in both animal models and humans. This Review provides a detailed overview of mRNA vaccines and considers future directions and challenges in advancing this promising vaccine platform to widespread therapeutic use

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Pardi N, Secreto AJ, Shan X, Debonera F, Glover J, Yi Y, Muramatsu H, Ni H, Mui BL, Tam YK, Shaheen F, Collman RG, Karikó K, Danet-Desnoyers GA, Madden TD, Hope MJ, Weissman D.

Administration of nucleoside-modified mRNA encoding broadly neutralizing antibody protects humanized mice from HIV-1 challenge.

Nat Commun. 2017 Mar 2;8:14630.

doi: 10.1038/ncomms14630; PMID: 28251988; PMCID: PMC5337964.

Monoclonal antibodies are one of the fastest growing classes of pharmaceutical products, however, their potential is limited by the high cost of development and manufacturing. Here we present a safe and cost-effective platform for in vivo expression of therapeutic antibodies using nucleoside-modified mRNA. To demonstrate feasibility and protective efficacy, nucleoside-modified mRNAs encoding the light and heavy chains of the broadly neutralizing anti-HIV-1 antibody VRC01 are generated and encapsulated into lipid nanoparticles. Systemic administration of 1.4 mg kg-1 of mRNA into mice results in ∼170 μg ml-1 VRC01 antibody concentrations in the plasma 24 h post injection. Weekly injections of 1 mg kg-1 of mRNA into immunodeficient mice maintain trough VRC01 levels above 40 μg ml-1. Most importantly, the translated antibody from a single injection of VRC01 mRNA protects humanized mice from intravenous HIV-1 challenge, demonstrating that nucleoside-modified mRNA represents a viable delivery platform for passive immunotherapy against HIV-1 with expansion to a variety of diseases.

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Pardi N, Hogan MJ, Pelc RS, Muramatsu H, Andersen H, DeMaso CR, Dowd KA, Sutherland LL, Scearce RM, Parks R, Wagner W, Granados A, Greenhouse J, Walker M, Willis E, Yu JS, McGee CE, Sempowski GD, Mui BL, Tam YK, Huang YJ, Vanlandingham D, Holmes VM, Balachandran H, Sahu S, Lifton M, Higgs S, Hensley SE, Madden TD, Hope MJ, Karikó K, Santra S, Graham BS, Lewis MG, Pierson TC, Haynes BF, Weissman D.

Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination.

Nature. 2017 Mar 9;543(7644):248-251.

doi: 10.1038/nature21428; PMID: 28151488; PMCID: PMC5344708.

Zika virus (ZIKV) has recently emerged as a pandemic associated with severe neuropathology in newborns and adults. There are no ZIKV-specific treatments or preventatives. Therefore, the development of a safe and effective vaccine is a high priority. Messenger RNA (mRNA) has emerged as a versatile and highly effective platform to deliver vaccine antigens and therapeutic proteins. Here we demonstrate that a single low-dose intradermal immunization with lipid-nanoparticle-encapsulated nucleoside-modified mRNA (mRNA-LNP) encoding the pre-membrane and envelope glycoproteins of a strain from the ZIKV outbreak in 2013 elicited potent and durable neutralizing antibody responses in mice and non-human primates. Immunization with 30 μg of nucleoside-modified ZIKV mRNA-LNP protected mice against ZIKV challenges at 2 weeks or 5 months after vaccination, and a single dose of 50 μg was sufficient to protect non-human primates against a challenge at 5 weeks after vaccination. These data demonstrate that nucleoside-modified mRNA-LNP elicits rapid and durable protective immunity and therefore represents a new and promising vaccine candidate for the global fight against ZIKV.

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Pardi N, Tuyishime S, Muramatsu H, Kariko K, Mui BL, Tam YK, Madden TD, Hope MJ, Weissman D.

Expression kinetics of nucleoside-modified mRNA delivered in lipid nanoparticles to mice by various routes.

J Control Release. 2015 Nov 10;217:345-51.

doi: 10.1016/j.jconrel.2015.08.007; PMID: 26264835; PMCID: PMC4624045.

In recent years, in vitro transcribed messenger RNA (mRNA) has emerged as a potential therapeutic platform. To fulfill its promise, effective delivery of mRNA to specific cell types and tissues needs to be achieved. Lipid nanoparticles (LNPs) are efficient carriers for short-interfering RNAs and have entered clinical trials. However, little is known about the potential of LNPs to deliver mRNA. Here, we generated mRNA-LNPs by incorporating HPLC purified, 1-methylpseudouridine-containing mRNA comprising codon-optimized firefly luciferase into stable LNPs. Mice were injected with 0.005-0.250mg/kg doses of mRNA-LNPs by 6 different routes and high levels of protein translation could be measured using in vivo imaging. Subcutaneous, intramuscular and intradermal injection of the LNP-encapsulated mRNA translated locally at the site of injection for up to 10days. For several days, high levels of protein production could be achieved in the lung from the intratracheal administration of mRNA. Intravenous and intraperitoneal and to a lesser extent intramuscular and intratracheal deliveries led to trafficking of mRNA-LNPs systemically resulting in active translation of the mRNA in the liver for 1-4 days. Our results demonstrate that LNPs are appropriate carriers for mRNA in vivo and have the potential to become valuable tools for delivering mRNA encoding therapeutic proteins.

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2023

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Deák C, Pardi N, Miklósi Á.

Innovation in the 21st century: following the footsteps of Katalin Karikó.

Biol Futur. 2023 May 22.

doi: 10.1007/s42977-023-00161-8; PMID: 37213055; PMCID: PMC10201475.

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Gál L, Bellák T, Marton A, Fekécs Z, Weissman D, Török D, Biju R, Vizler C, Kristóf R, Beattie MB, Lin PJC, Pardi N, Nógrádi A, Pajer K.

Restoration of Motor Function through Delayed Intraspinal Delivery of Human IL-10-Encoding Nucleoside-Modified mRNA after Spinal Cord Injury.

Research (Wash D C). 2023;6:0056.

doi: 10.34133/research.0056; Epub 2023 Mar 9; PMID: 36930811; PMCID: PMC10013810.

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Ramos da Silva J, Bitencourt Rodrigues K, Formoso Pelegrin G, Silva Sales N, Muramatsu H, de Oliveira Silva M, Porchia BFMM, Moreno ACR, Aps LRMM, Venceslau-Carvalho AA, Tombácz I, Fotoran WL, Karikó K, Lin PJC, Tam YK, de Oliveira Diniz M, Pardi N*, de Souza Ferreira LC.

Single immunizations of self-amplifying or non-replicating mRNA-LNP vaccines control HPV-associated tumors in mice.

Sci Transl Med. 2023 Mar 3:eabn3464.

doi: 10.1126/scitranslmed.abn3464.; PMID: 36867683.

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Cesaro A, Lin S, Pardi N, de la Fuente-Nunez C.

Advanced delivery systems for peptide antibiotics.

Adv Drug Deliv Rev. 2023 Feb 17:114733.

doi: 10.1016/j.addr.2023.114733; PMID: 36804008.

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Amanat F, Clark J, Carreño JM, Strohmeier S, Yellin T, Meade PS, Bhavsar D, Muramatsu H, Sun W, Coughlan L, Pardi N, Krammer F.

Immunity to Seasonal Coronavirus Spike Proteins Does Not Protect from SARS-CoV-2 Challenge in a Mouse Model but Has No Detrimental Effect on Protection Mediated by COVID-19 mRNA Vaccination.

J Virol. 2023 Feb 13:e0166422.

doi: 10.1128/jvi.01664-22; PMID: 36779758.

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Melamed JR, Yerneni SS, Arral ML, LoPresti ST, Chaudhary N, Sehrawat A, Muramatsu H, Alameh MG, Pardi N, Weissman D, Gittes GK, Whitehead KA.

Ionizable lipid nanoparticles deliver mRNA to pancreatic β cells via macrophage-mediated gene transfer.

Sci Adv. 2023 Jan 27;9(4):eade1444.

doi: 10.1126/sciadv.ade1444. Epub 2023 Jan 27. PMID: 36706177.

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Schiepers A, van 't Wout MFL, Greaney AJ, Zang T, Muramatsu H, Lin PJC, Tam YK, Mesin L, Starr TN, Bieniasz PD, Pardi N, Bloom JD, Victora GD.

Molecular fate-mapping of serum antibody responses to repeat immunization.

Nature. 2023 Jan 16.

doi: 10.1038/s41586-023-05715-3; PMID: 36646114.

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2022

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Gouma S, Furey C, Santos JJS, Parkhouse K, Weirick M, Muramatsu H, Pardi N, Fan SHY, Weissman D, Hensley SE.

Nucleoside-Modified mRNA-Based Influenza Vaccines Circumvent Problems Associated with H3N2 Vaccine Strain Egg Adaptation.

J Virol. 2022 Dec 19:e0172322.

doi: 10.1128/jvi.01723-22; PMID: 36533954.

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van de Ven K, Lanfermeijer J, van Dijken H, Muramatsu H, Vilas Boas de Melo C, Lenz S, Peters F, Beattie MB, Lin PJC, Ferreira JA, van den Brand J, van Baarle D, Pardi N*, de Jonge J.

A universal influenza mRNA vaccine candidate boosts T cell responses and reduces zoonotic influenza virus disease in ferrets.

Sci Adv. 2022 Dec 14;8(50):eadc9937.

doi: 10.1126/sciadv.adc9937; PMID: 36516261.

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Arevalo CP, Bolton MJ, Le Sage V, Ye N, Furey C, Muramatsu H, Alameh MG, Pardi N, Drapeau EM, Parkhouse K, Garretson T, Morris JS, Moncla LH, Tam YK, Fan SHY, Lakdawala SS, Weissman D, Hensley SE.

A multivalent nucleoside-modified mRNA vaccine against all known influenza virus subtypes.

Science. 2022 Nov 25;378(6622):899-904.

doi: 10.1126/science.abm0271; PMID: 36423275.

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Nakandakari-Higa S, Parsa R, Reis BS, de Carvalho RVH, Mesin L, Hoffmann HH, Bortolatto J, Muramatsu H, Lin PJC, Bilate AM, Rice CM, Pardi N, Mucida D, Victora GD, Canesso MCC.

A minimally-edited mouse model for infection with multiple SARS-CoV-2 strains.

Front Immunol. 2022 Nov 14;13:1007080.

doi: 10.3389/fimmu.2022.1007080; PMID: 36451809; PMCID: PMC9703079.

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Verbeke R, Hogan MJ, Loré K, Pardi N.*

Innate immune mechanisms of mRNA vaccines.

Immunity. 2022 Nov 8;55(11):1993-2005.

doi: 10.1016/j.immuni.2022.10.014; PMID: 36351374; PMCID: PMC9641982.

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McMahon M, O'Dell G, Tan J, Sárközy A, Vadovics M, Carreño JM, Puente-Massaguer E, Muramatsu H, Bajusz C, Rijnink W, Beattie M, Tam YK, Kirkpatrick Roubidoux E, Francisco I, Strohmeier S, Kanekiyo M, Graham BS, Krammer F, Pardi N.*

Assessment of a quadrivalent nucleoside-modified mRNA vaccine that protects against group 2 influenza viruses.

Proc Natl Acad Sci U S A. 2022 Nov 8;119(45):e2206333119.

doi: 10.1073/pnas.2206333119; PMID: 36322769.

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Li D, Martinez DR, Schäfer A, Chen H, Barr M, Sutherland LL, Lee E, Parks R, Mielke D, Edwards W, Newman A, Bock KW, Minai M, Nagata BM, Gagne M, Douek DC, DeMarco CT, Denny TN, Oguin TH 3rd, Brown A, Rountree W, Wang Y, Mansouri K, Edwards RJ, Ferrari G, Sempowski GD, Eaton A, Tang J, Cain DW, Santra S, Pardi N, Weissman D, Tomai MA, Fox CB, Moore IN, Andersen H, Lewis MG, Golding H, Seder R, Khurana S, Baric RS, Montefiori DC, Saunders KO, Haynes BF.

Breadth of SARS-CoV-2 neutralization and protection induced by a nanoparticle vaccine.

Nat Commun. 2022 Oct 23;13(1):6309.

doi: 10.1038/s41467-022-33985-4; PMID: 36274085; PMCID: PMC9588772.

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Carreño JM, Singh G, Tcheou J, Srivastava K, Gleason C, Muramatsu H, Desai P, Aberg JA, Miller RL, Study Group P, Pardi N, Simon V, Krammer F.

mRNA-1273 but not BNT162b2 induces antibodies against polyethylene glycol (PEG) contained in mRNA-based vaccine formulations.

Vaccine. 2022 Oct 6;40(42):6114-6124.

doi: 10.1016/j.vaccine.2022.08.024; PMID: 36115801; PMCID: PMC9474432.

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Jitthamstaporn S, Inthong R, Audomsun D, Chanasit S, Thanasarnthungcharoen C, Lin PJC, Weissman D, Pardi N, Jacquet A.

Nucleoside-modified mRNA vaccines yield robust blocking antibody responses against major house dust mite allergens.

Allergy. 2022 Sep 22:10.1111/all.15527.

doi: 10.1111/all.15527; PMID: 36136090; PMCID: PMC9538380.

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Pardi N*, Carreño JM, O'Dell G, Tan J, Bajusz C, Muramatsu H, Rijnink W, Strohmeier S, Loganathan M, Bielak D, Sung MMH, Tam YK, Krammer F, McMahon M.

Development of a pentavalent broadly protective nucleoside-modified mRNA vaccine against influenza B viruses.

Nat Commun. 2022 Aug 9;13(1):4677.

doi: 10.1038/s41467-022-32149-8; PMID: 35945226; PMCID: PMC9362976.

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Muramatsu H, Lam K, Bajusz C, Laczkó D, Karikó K, Schreiner P, Martin A, Lutwyche P, Heyes J, Pardi N.*

Lyophilization provides long-term stability for a lipid nanoparticle-formulated, nucleoside-modified mRNA vaccine.

Mol Ther. 2022 May 4;30(5):1941-1951.

doi: 10.1016/j.ymthe.2022.02.001; PMID: 35131437; PMCID: PMC8815268.

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Parhiz H, Brenner JS, Patel PN, Papp TE, Shahnawaz H, Li Q, Shi R, Zamora ME, Yadegari A, Marcos-Contreras OA, Natesan A, Pardi N, Shuvaev VV, Kiseleva R, Myerson JW, Uhler T, Riley RS, Han X, Mitchell MJ, Lam K, Heyes J, Weissman D, Muzykantov VR.

Added to pre-existing inflammation, mRNA-lipid nanoparticles induce inflammation exacerbation (IE).

J Control Release. 2022 Apr;344:50-61.

doi: 10.1016/j.jconrel.2021.12.027; PMID: 34953981; PMCID: PMC8695324.

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Mu Z, Wiehe K, Saunders KO, Henderson R, Cain DW, Parks R, Martik D, Mansouri K, Edwards RJ, Newman A, Lu X, Xia SM, Eaton A, Bonsignori M, Montefiori D, Han Q, Venkatayogi S, Evangelous T, Wang Y, Rountree W, Korber B, Wagh K, Tam Y, Barbosa C, Alam SM, Williams WB, Tian M, Alt FW, Pardi N, Weissman D, Haynes BF.

mRNA-encoded HIV-1 Env trimer ferritin nanoparticles induce monoclonal antibodies that neutralize heterologous HIV-1 isolates in mice.

Cell Rep. 2022 Mar 15;38(11):110514.

doi: 10.1016/j.celrep.2022.110514. PMID: 35294883; PMCID: PMC8922439.

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Appelberg S, John L, Pardi N, Végvári Á, Bereczky S, Ahlén G, Monteil V, Abdurahman S, Mikaeloff F, Beattie M, Tam Y, Sällberg M, Neogi U, Weissman D, Mirazimi A.

Nucleoside-Modified mRNA Vaccines Protect IFNAR-/- Mice against Crimean-Congo Hemorrhagic Fever Virus Infection.

J Virol. 2022 Feb 9;96(3):e0156821.

doi: 10.1128/JVI.01568-21; PMID: 34817199; PMCID: PMC8826901.

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Melamed JR, Hajj KA, Chaudhary N, Strelkova D, Arral ML, Pardi N, Alameh MG, Miller JB, Farbiak L, Siegwart DJ, Weissman D, Whitehead KA.

Lipid nanoparticle chemistry determines how nucleoside base modifications alter mRNA delivery.

J Control Release. 2022 Jan;341:206-214.

doi: 10.1016/j.jconrel.2021.11.022; PMID: 34801660; PMCID: PMC8905090.

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Hogan MJ, Pardi N.*

mRNA Vaccines in the COVID-19 Pandemic and Beyond.

Annu Rev Med. 2022 Jan 27;73:17-39.

doi: 10.1146/annurev-med-042420-112725. PMID: 34669432.

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2021

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Matias J, Kurokawa C, Sajid A, Narasimhan S, Arora G, Diktas H, Lynn GE, DePonte K, Pardi N, Valenzuela JG, Weissman D, Fikrig E.

Tick immunity using mRNA, DNA and protein-based Salp14 delivery strategies. Vaccine. 2021 Dec 20;39(52):7661-7668.

doi: 10.1016/j.vaccine.2021.11.003; PMID: 34862075; PMCID: PMC8671329.

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Alameh MG, Tombácz I, Bettini E, Lederer K, Sittplangkoon C, Wilmore JR, Gaudette BT, Soliman OY, Pine M, Hicks P, Manzoni TB, Knox JJ, Johnson JL, Laczkó D, Muramatsu H, Davis B, Meng W, Rosenfeld AM, Strohmeier S, Lin PJC, Mui BL, Tam YK, Karikó K, Jacquet A, Krammer F, Bates P, Cancro MP, Weissman D, Luning Prak ET, Allman D, Locci M, Pardi N.*

Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses.

Immunity. 2021 Dec 14;54(12):2877-2892.e7.

doi: 10.1016/j.immuni.2021.11.001.  PMID: 34852217; PMCID: PMC8566475.

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Awasthi S, Knox JJ, Desmond A, Alameh MG, Gaudette BT, Lubinski JM, Naughton A, Hook LM, Egan KP, Tam YK, Pardi N, Allman D, Luning Prak ET, Cancro MP, Weissman D, Cohen GH, Friedman HM.

Trivalent nucleoside-modified mRNA vaccine yields durable memory B cell protection against genital herpes in preclinical models.

J Clin Invest. 2021 Dec 1;131(23):e152310.

doi: 10.1172/JCI152310. PMID: 34618692; PMCID: PMC8631595.

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Tombácz I, Laczkó D, Shahnawaz H, Muramatsu H, Natesan A, Yadegari A, Papp TE, Alameh MG, Shuvaev V, Mui BL, Tam YK, Muzykantov V, Pardi N, Weissman D, Parhiz H.

Highly efficient CD4+ T cell targeting and genetic recombination using engineered CD4+ cell-homing mRNA-LNPs.

Mol Ther. 2021 Nov 3;29(11):3293-3304.

doi: 10.1016/j.ymthe.2021.06.004; PMID: 34091054; PMCID: PMC8571164.

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Knudson CJ, Alves-Peixoto P, Muramatsu H, Stotesbury C, Tang L, Lin PJC, Tam YK, Weissman D, Pardi N, Sigal LJ.

Lipid-nanoparticle-encapsulated mRNA vaccines induce protective memory CD8 T cells against a lethal viral infection.

Mol Ther. 2021 Sep 1;29(9):2769-2781.

doi: 10.1016/j.ymthe.2021.05.011; PMID: 33992803; PMCID: PMC8417516.

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Martinez DR, Schäfer A, Leist SR, De la Cruz G, West A, Atochina-Vasserman EN, Lindesmith LC, Pardi N, Parks R, Barr M, Li D, Yount B, Saunders KO, Weissman D, Haynes BF, Montgomery SA, Baric RS.

Chimeric spike mRNA vaccines protect against Sarbecovirus challenge in mice.

Science. 2021 Aug 27;373(6558):991-998.

doi: 10.1126/science.abi4506; PMID: 34214046; PMCID: PMC8899822.

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Rothgangl T, Dennis MK, Lin PJC, Oka R, Witzigmann D, Villiger L, Qi W, Hruzova M, Kissling L, Lenggenhager D, Borrelli C, Egli S, Frey N, Bakker N, Walker JA 2nd, Kadina AP, Victorov DV, Pacesa M, Kreutzer S, Kontarakis Z, Moor A, Jinek M, Weissman D, Stoffel M, van Boxtel R, Holden K, Pardi N, Thöny B, Häberle J, Tam YK, Semple SC, Schwank G.

In vivo adenine base editing of PCSK9 in macaques reduces LDL cholesterol levels.

Nat Biotechnol. 2021 Aug;39(8):949-957.

doi: 10.1038/s41587-021-00933-4. PMID: 34012094; PMCID: PMC8352781.

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Mallory KL, Taylor JA, Zou X, Waghela IN, Schneider CG, Sibilo MQ, Punde NM, Perazzo LC, Savransky T, Sedegah M, Dutta S, Janse CJ, Pardi N, Lin PJC, Tam YK, Weissman D, Angov E.

Messenger RNA expressing PfCSP induces functional, protective immune responses against malaria in mice.

NPJ Vaccines. 2021 Jun 18;6(1):84.

doi: 10.1038/s41541-021-00345-0; PMID: 34145286; PMCID: PMC8213722.

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Freyn AW, Pine M, Rosado VC, Benz M, Muramatsu H, Beattie M, Tam YK, Krammer F, Palese P, Nachbagauer R, McMahon M, Pardi N.*

Antigen modifications improve nucleoside-modified mRNA-based influenza virus vaccines in mice.

Mol Ther Methods Clin Dev. 2021 Jun 12;22:84-95.

doi: 10.1016/j.omtm.2021.06.003; PMID: 34485597; PMCID: PMC8390451.

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Szőke D, Kovács G, Kemecsei É, Bálint L, Szoták-Ajtay K, Aradi P, Styevkóné Dinnyés A, Mui BL, Tam YK, Madden TD, Karikó K, Kataru RP, Hope MJ, Weissman D, Mehrara BJ, Pardi N*, Jakus Z.

Nucleoside-modified VEGFC mRNA induces organ-specific lymphatic growth and reverses experimental lymphedema.

Nat Commun. 2021 Jun 8;12(1):3460.

doi: 10.1038/s41467-021-23546-6. PMID: 34103491; PMCID: PMC8187400.

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Saunders KO, Lee E, Parks R, Martinez DR, Li D, Chen H, Edwards RJ, Gobeil S, Barr M, Mansouri K, Alam SM, Sutherland LL, Cai F, Sanzone AM, Berry M, Manne K, Bock KW, Minai M, Nagata BM, Kapingidza AB, Azoitei M, Tse LV, Scobey TD, Spreng RL, Rountree RW, DeMarco CT, Denny TN, Woods CW, Petzold EW, Tang J, Oguin TH 3rd, Sempowski GD, Gagne M, Douek DC, Tomai MA, Fox CB, Seder R, Wiehe K, Weissman D, Pardi N, Golding H, Khurana S, Acharya P, Andersen H, Lewis MG, Moore IN, Montefiori DC, Baric RS, Haynes BF.

Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses.

Nature. 2021 Jun;594(7864):553-559.

doi: 10.1038/s41586-021-03594-0; PMID: 33971664; PMCID: PMC8528238.

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Pardi N.

mRNA Innovates the Vaccine Field.

Vaccines (Basel). 2021 May 11;9(5):486.

doi: 10.3390/vaccines9050486; PMID: 34064557; PMCID: PMC8151794.

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Saunders KO, Pardi N, Parks R, Santra S, Mu Z, Sutherland L, Scearce R, Barr M, Eaton A, Hernandez G, Goodman D, Hogan MJ, Tombacz I, Gordon DN, Rountree RW, Wang Y, Lewis MG, Pierson TC, Barbosa C, Tam Y, Matyas GR, Rao M, Beck Z, Shen X, Ferrari G, Tomaras GD, Montefiori DC, Weissman D, Haynes BF.

Lipid nanoparticle encapsulated nucleoside-modified mRNA vaccines elicit polyfunctional HIV-1 antibodies comparable to proteins in nonhuman primates.

NPJ Vaccines. 2021 Apr 9;6(1):50.

doi: 10.1038/s41541-021-00307-6; PMID: 33837212; PMCID: PMC8035178.

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Rizvi F, Everton E, Smith AR, Liu H, Osota E, Beattie M, Tam Y, Pardi N, Weissman D, Gouon-Evans V.

Murine liver repair via transient activation of regenerative pathways in hepatocytes using lipid nanoparticle-complexed nucleoside-modified mRNA.

Nat Commun. 2021 Jan 27;12(1):613.

doi: 10.1038/s41467-021-20903-3; PMID: 33504774; PMCID: PMC7840919.

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Weissman D, Alameh MG, de Silva T, Collini P, Hornsby H, Brown R, LaBranche CC, Edwards RJ, Sutherland L, Santra S, Mansouri K, Gobeil S, McDanal C, Pardi N, Hengartner N, Lin PJC, Tam Y, Shaw PA, Lewis MG, Boesler C, Şahin U, Acharya P, Haynes BF, Korber B, Montefiori DC.

D614G Spike Mutation Increases SARS CoV-2 Susceptibility to Neutralization.

Cell Host Microbe. 2021 Jan 13;29(1):23-31.e4.

doi: 10.1016/j.chom.2020.11.012; PMID: 33306985; PMCID: PMC7707640.

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Tombácz I, Weissman D, Pardi N.*

Vaccination with Messenger RNA: A Promising Alternative to DNA Vaccination.

Methods Mol Biol. 2021;2197:13-31.

doi: 10.1007/978-1-0716-0872-2_2. PMID: 32827130.

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2020

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Lederer K, Castaño D, Gómez Atria D, Oguin TH 3rd, Wang S, Manzoni TB, Muramatsu H, Hogan MJ, Amanat F, Cherubin P, Lundgreen KA, Tam YK, Fan SHY, Eisenlohr LC, Maillard I, Weissman D, Bates P, Krammer F, Sempowski GD, Pardi N, Locci M.

SARS-CoV-2 mRNA Vaccines Foster Potent Antigen-Specific Germinal Center Responses Associated with Neutralizing Antibody Generation.

Immunity. 2020 Dec 15;53(6):1281-1295.e5.

doi: 10.1016/j.immuni.2020.11.009; PMID: 33296685; PMCID: PMC7680029.

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Pardi N*, Weissman D.

Development of vaccines and antivirals for combating viral pandemics.

Nat Biomed Eng. 2020 Dec;4(12):1128-1133.

doi: 10.1038/s41551-020-00658-w. PMID: 33293724; PMCID: PMC8336060.

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LaTourette PC 2nd, Awasthi S, Desmond A, Pardi N, Cohen GH, Weissman D, Friedman HM.

Protection against herpes simplex virus type 2 infection in a neonatal murine model using a trivalent nucleoside-modified mRNA in lipid nanoparticle vaccine.

Vaccine. 2020 Nov 3;38(47):7409-7413.

doi: 10.1016/j.vaccine.2020.09.079; PMID: 33041105; PMCID: PMC7545304.

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Laczkó D, Hogan MJ, Toulmin SA, Hicks P, Lederer K, Gaudette BT, Castaño D, Amanat F, Muramatsu H, Oguin TH 3rd, Ojha A, Zhang L, Mu Z, Parks R, Manzoni TB, Roper B, Strohmeier S, Tombácz I, Arwood L, Nachbagauer R, Karikó K, Greenhouse J, Pessaint L, Porto M, Putman-Taylor T, Strasbaugh A, Campbell TA, Lin PJC, Tam YK, Sempowski GD, Farzan M, Choe H, Saunders KO, Haynes BF, Andersen H, Eisenlohr LC, Weissman D, Krammer F, Bates P, Allman D, Locci M, Pardi N.*

A Single Immunization with Nucleoside-Modified mRNA Vaccines Elicits Strong Cellular and Humoral Immune Responses against SARS-CoV-2 in Mice.

Immunity. 2020 Oct 13;53(4):724-732.e7.

doi: 10.1016/j.immuni.2020.07.019; PMID: 32783919; PMCID: PMC7392193.

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Pardi N*, Hogan MJ, Weissman D.

Recent advances in mRNA vaccine technology.

Curr Opin Immunol. 2020 Aug;65:14-20.

doi: 10.1016/j.coi.2020.01.008; PMID: 32244193.

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Egan KP, Hook LM, Naughton A, Pardi N, Awasthi S, Cohen GH, Weissman D, Friedman HM.

An HSV-2 nucleoside-modified mRNA genital herpes vaccine containing glycoproteins gC, gD, and gE protects mice against HSV-1 genital lesions and latent infection.

PLoS Pathog. 2020 Jul 27;16(7):e1008795.

doi: 10.1371/journal.ppat.1008795; PMID: 32716975; PMCID: PMC7410331.

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Freyn AW, Ramos da Silva J, Rosado VC, Bliss CM, Pine M, Mui BL, Tam YK, Madden TD, de Souza Ferreira LC, Weissman D, Krammer F, Coughlan L, Palese P, Pardi N*, Nachbagauer R.

A Multi-Targeting, Nucleoside-Modified mRNA Influenza Virus Vaccine Provides Broad Protection in Mice.

Mol Ther. 2020 Jul 8;28(7):1569-1584.

doi: 10.1016/j.ymthe.2020.04.018; PMID: 32359470; PMCID: PMC7335735.

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Raj DK, Das Mohapatra A, Jnawali A, Zuromski J, Jha A, Cham-Kpu G, Sherman B, Rudlaff RM, Nixon CE, Hilton N, Oleinikov AV, Chesnokov O, Merritt J, Pond-Tor S, Burns L, Jolly G, Ben Mamoun C, Kabyemela E, Muehlenbachs A, Lambert L, Orr-Gonzalez S, Gnädig NF, Fidock DA, Park S, Dvorin JD, Pardi N, Weissman D, Mui BL, Tam YK, Friedman JF, Fried M, Duffy PE, Kurtis JD.

Anti-PfGARP activates programmed cell death of parasites and reduces severe malaria.

Nature. 2020 Jun;582(7810):104-108.

doi: 10.1038/s41586-020-2220-1; PMID: 32427965; PMCID: PMC7372601.

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Johnson JL, Rosenthal RL, Knox JJ, Myles A, Naradikian MS, Madej J, Kostiv M, Rosenfeld AM, Meng W, Christensen SR, Hensley SE, Yewdell J, Canaday DH, Zhu J, McDermott AB, Dori Y, Itkin M, Wherry EJ, Pardi N, Weissman D, Naji A, Prak ETL, Betts MR, Cancro MP.

The Transcription Factor T-bet Resolves Memory B Cell Subsets with Distinct Tissue Distributions and Antibody Specificities in Mice and Humans.

Immunity. 2020 May 19;52(5):842-855.e6.

doi: 10.1016/j.immuni.2020.03.020; PMID: 32353250; PMCID: PMC7242168.

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Alameh MG, Weissman D, Pardi N.

Messenger RNA-Based Vaccines Against Infectious Diseases.

Curr Top Microbiol Immunol. 2020 Apr 17.

doi: 10.1007/82_2020_202; PMID: 32300916.

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Nelson CS, Jenks JA, Pardi N, Goodwin M, Roark H, Edwards W, McLellan JS, Pollara J, Weissman D, Permar SR.

Human Cytomegalovirus Glycoprotein B Nucleoside-Modified mRNA Vaccine Elicits Antibody Responses with Greater Durability and Breadth than MF59-Adjuvanted gB Protein Immunization.

J Virol. 2020 Apr 16;94(9):e00186-20.

doi: 10.1128/JVI.00186-20; PMID: 32051265; PMCID: PMC7163130.

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Marcos-Contreras OA, Greineder CF, Kiseleva RY, Parhiz H, Walsh LR, Zuluaga-Ramirez V, Myerson JW, Hood ED, Villa CH, Tombacz I, Pardi N, Seliga A, Mui BL, Tam YK, Glassman PM, Shuvaev VV, Nong J, Brenner JS, Khoshnejad M, Madden T, Weissmann D, Persidsky Y, Muzykantov VR.

Selective targeting of nanomedicine to inflamed cerebral vasculature to enhance the blood-brain barrier.

Proc Natl Acad Sci U S A. 2020 Feb 18;117(7):3405-3414.

doi: 10.1073/pnas.1912012117; PMID: 32005712; PMCID: PMC7035611.

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Willis E, Pardi N, Parkhouse K, Mui BL, Tam YK, Weissman D, Hensley SE.

Nucleoside-modified mRNA vaccination partially overcomes maternal antibody inhibition of de novo immune responses in mice.

Sci Transl Med. 2020 Jan 8;12(525):eaav5701.

doi: 10.1126/scitranslmed.aav5701; PMID: 31915303; PMCID: PMC7339908.

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2019

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Awasthi S, Hook LM, Pardi N, Wang F, Myles A, Cancro MP, Cohen GH, Weissman D, Friedman HM.

Nucleoside-modified mRNA encoding HSV-2 glycoproteins C, D, and E prevents clinical and subclinical genital herpes.

Sci Immunol. 2019 Sep 20;4(39):eaaw7083.

doi: 10.1126/sciimmunol.aaw7083; PMID: 31541030; PMCID: PMC6822172.

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Pardi N*, LaBranche CC, Ferrari G, Cain DW, Tombácz I, Parks RJ, Muramatsu H, Mui BL, Tam YK, Karikó K, Polacino P, Barbosa CJ, Madden TD, Hope MJ, Haynes BF, Montefiori DC, Hu SL, Weissman D.

Characterization of HIV-1 Nucleoside-Modified mRNA Vaccines in Rabbits and Rhesus Macaques.

Mol Ther Nucleic Acids. 2019 Apr 15;15:36-47.

doi: 10.1016/j.omtn.2019.03.003; PMID: 30974332; PMCID: PMC6454128.

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Foster JB, Choudhari N, Perazzelli J, Storm J, Hofmann TJ, Jain P, Storm PB, Pardi N, Weissman D, Waanders AJ, Grupp SA, Karikó K, Resnick AC, Barrett DM.

Purification of mRNA Encoding Chimeric Antigen Receptor Is Critical for Generation of a Robust T-Cell Response.

Hum Gene Ther. 2019 Feb;30(2):168-178.

doi: 10.1089/hum.2018.145; PMID: 30024272; PMCID: PMC6383579.

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2018

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Parhiz H, Shuvaev VV, Pardi N, Khoshnejad M, Kiseleva RY, Brenner JS, Uhler T, Tuyishime S, Mui BL, Tam YK, Madden TD, Hope MJ, Weissman D, Muzykantov VR.

PECAM-1 directed re-targeting of exogenous mRNA providing two orders of magnitude enhancement of vascular delivery and expression in lungs independent of apolipoprotein E-mediated uptake.

J Control Release. 2018 Dec 10;291:106-115.

doi: 10.1016/j.jconrel.2018.10.015; PMID: 30336167; PMCID: PMC6477695.

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Pardi N, Parkhouse K, Kirkpatrick E, McMahon M, Zost SJ, Mui BL, Tam YK, Karikó K, Barbosa CJ, Madden TD, Hope MJ, Krammer F, Hensley SE, Weissman D.

Nucleoside-modified mRNA immunization elicits influenza virus hemagglutinin stalk-specific antibodies.

Nat Commun. 2018 Aug 22;9(1):3361.

doi: 10.1038/s41467-018-05482-0; PMID: 30135514; PMCID: PMC6105651.

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Pardi N*, Hogan MJ, Naradikian MS, Parkhouse K, Cain DW, Jones L, Moody MA, Verkerke HP, Myles A, Willis E, LaBranche CC, Montefiori DC, Lobby JL, Saunders KO, Liao HX, Korber BT, Sutherland LL, Scearce RM, Hraber PT, Tombácz I, Muramatsu H, Ni H, Balikov DA, Li C, Mui BL, Tam YK, Krammer F, Karikó K, Polacino P, Eisenlohr LC, Madden TD, Hope MJ, Lewis MG, Lee KK, Hu SL, Hensley SE, Cancro MP, Haynes BF, Weissman D.

Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses.

J Exp Med. 2018 Jun 4;215(6):1571-1588.

doi: 10.1084/jem.20171450; PMID: 29739835; PMCID: PMC5987916.

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Scorza FB, Pardi N.*

New Kids on the Block: RNA-Based Influenza Virus Vaccines.

Vaccines (Basel). 2018 Apr 1;6(2):20.

doi: 10.3390/vaccines6020020; PMID: 29614788; PMCID: PMC6027361.

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Pardi N, Hogan MJ, Porter FW, Weissman D.

mRNA vaccines - a new era in vaccinology.

Nat Rev Drug Discov. 2018 Apr;17(4):261-279.

doi: 10.1038/nrd.2017.243; PMID: 29326426; PMCID: PMC5906799.

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Hogan MJ, Conde-Motter A, Jordan APO, Yang L, Cleveland B, Guo W, Romano J, Ni H, Pardi N, LaBranche CC, Montefiori DC, Hu SL, Hoxie JA, Weissman D.

Increased surface expression of HIV-1 envelope is associated with improved antibody response in vaccinia prime/protein boost immunization.

Virology. 2018 Jan 15;514:106-117.

doi: 10.1016/j.virol.2017.10.013; PMID: 29175625; PMCID: PMC5770335.

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2017

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Pardi N, Hogan MJ, Pelc RS, Muramatsu H, Andersen H, DeMaso CR, Dowd KA, Sutherland LL, Scearce RM, Parks R, Wagner W, Granados A, Greenhouse J, Walker M, Willis E, Yu JS, McGee CE, Sempowski GD, Mui BL, Tam YK, Huang YJ, Vanlandingham D, Holmes VM, Balachandran H, Sahu S, Lifton M, Higgs S, Hensley SE, Madden TD, Hope MJ, Karikó K, Santra S, Graham BS, Lewis MG, Pierson TC, Haynes BF, Weissman D.

Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination.

Nature. 2017 Mar 9;543(7644):248-251.

doi: 10.1038/nature21428; PMID: 28151488; PMCID: PMC5344708.

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Pardi N, Secreto AJ, Shan X, Debonera F, Glover J, Yi Y, Muramatsu H, Ni H, Mui BL, Tam YK, Shaheen F, Collman RG, Karikó K, Danet-Desnoyers GA, Madden TD, Hope MJ, Weissman D.

Administration of nucleoside-modified mRNA encoding broadly neutralizing antibody protects humanized mice from HIV-1 challenge.

Nat Commun. 2017 Mar 2;8:14630.

doi: 10.1038/ncomms14630; PMID: 28251988; PMCID: PMC5337964.

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Pardi N, Weissman D.

Measuring the Adjuvant Activity of RNA Vaccines.

Methods Mol Biol. 2017;1499:143-153.

doi: 10.1007/978-1-4939-6481-9_8. PMID: 27987147.

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Pardi N, Weissman D.

Nucleoside Modified mRNA Vaccines for Infectious Diseases.

Methods Mol Biol. 2017;1499:109-121.

doi: 10.1007/978-1-4939-6481-9_6. PMID: 27987145.

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2015

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Pardi N, Tuyishime S, Muramatsu H, Kariko K, Mui BL, Tam YK, Madden TD, Hope MJ, Weissman D.

Expression kinetics of nucleoside-modified mRNA delivered in lipid nanoparticles to mice by various routes.

J Control Release. 2015 Nov 10;217:345-51.

doi: 10.1016/j.jconrel.2015.08.007; PMID: 26264835; PMCID: PMC4624045.

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2013

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Weissman D, Pardi N, Muramatsu H, Karikó K.

HPLC purification of in vitro transcribed long RNA.

Methods Mol Biol. 2013;969:43-54.

doi: 10.1007/978-1-62703-260-5_3. PMID: 23296926.

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Pardi N, Muramatsu H, Weissman D, Karikó K.

In vitro transcription of long RNA containing modified nucleosides.

Methods Mol Biol. 2013;969:29-42.

doi: 10.1007/978-1-62703-260-5_2. PMID: 23296925.

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