COVID-19 vaccine mRNA-1273 elicits a protective immune profile in mice that is not associated with vaccine-enhanced disease upon SARS-CoV-2 challenge

DiPiazza, Anthony; Leist, Sarah R.; Abiona, Olubukola M.; Moliva, Juan I.; Werner, Anne P.; Minai, Mahnaz; Nagata, Bianca M.; Bock, Kevin W.; Phung, Emily; Schäfer, Alexandra; Dinnon, Kenneth H.; Chang, Lauren; Loomis, Rebecca J.; Boyoglu-Barnum, Seyhan; Alvarado, Gabriela; Sullivan, Nancy J.; Edwards, Darin K.; Morabito, Kaitlyn M.; Mascola, John R.; Carfı́, Andrea; Corbett, Kizzmekia S.; Moore, Ian N.; Baric, Ralph S.; Graham, Barney S.; Ruckwardt, Tracy J.

doi:10.1016/j.immuni.2021.06.018

Cited by 79 publications

(80 citation statements)

References 67 publications

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“…While pulmonary immunopathology accompanied by eosinophil accumulation in the respiratory tract upon SARS-CoV-2 infection has not been reported clinically with the widespread administration of either of the two COVID-19 mRNA vaccines and was not observed in preclinical studies of alum-adjuvanted inactivated SARS-CoV-2 vaccines in either murine or nonhuman primate pneumonia models, a recently reported parallel preclinical study between a SARS-CoV-2 mRNA vaccine and an inactivated vaccine adjuvanted with alum did show pulmonary immunopathology typical of eosinophil accumulation in mouse pneumonia models for the latter [40][41][42]44,45]. Considering the reportedly comparable strength of the neutralization antibody response induced between SARS-CoV-2 mRNA vaccines and alum-adjuvanted inactivated vaccines, the absence of cellular immunity accompanied by eosinophil-associated immunopathology may partially explain the lower protection of alum-adjuvanted inactivated SARS-CoV-2 vaccines in the real world, which has been certified as partial protection in preclinical studies of corresponding SARS-CoV-1 and MERS-CoV vaccines [20,[26][27][28][29].…”

Section: Discussionmentioning

confidence: 99%

An Established Th2-Oriented Response to an Alum-Adjuvanted SARS-CoV-2 Subunit Vaccine Is Not Reversible by Sequential Immunization with Nucleic Acid-Adjuvanted Th1-Oriented Subunit Vaccines

et al. 2021

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A recently reported parallel preclinical study between a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine and an inactivated SARS-CoV-2 vaccine adjuvanted with alum showed pulmonary immunopathology typical of eosinophil accumulation in a mouse pneumonia model for the latter, which implied a potential role of cellular immunity in the difference in the protection rate between these two forms of vaccines. For those who have been vaccinated with alum-adjuvanted subunit or inactivated SARS-CoV-2 vaccines, whether the Th2 responses that have been established and the absence of induced cellular immunity could be changed is an open question. Using two heterologous boosts with Th1-oriented CpG ODN-adjuvanted S1-based SARS-CoV-2 subunit vaccines for mice that were primed with two doses of Th2-oriented alum-adjuvanted S1-based SARS-CoV-2 subunit vaccines, we demonstrated that established Th2 orientation could not be reversed to Th1 orientation and that no cellular immunity was induced, which should have been induced if the boosting vaccines were used as the prime vaccines. These results remind us that if widely administered alum-adjuvanted SARS-CoV-2 vaccines cannot overcome the challenge of coronavirus disease 2019 (COVID-19) and that if cellular immunity is important for the efficacy of SARS-CoV-2 vaccines in the future, the choice of more powerful heterologous boosting vaccine forms that can induce cellular immunity should be considered very carefully before application.

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Section: Discussionmentioning

confidence: 99%

An Established Th2-Oriented Response to an Alum-Adjuvanted SARS-CoV-2 Subunit Vaccine Is Not Reversible by Sequential Immunization with Nucleic Acid-Adjuvanted Th1-Oriented Subunit Vaccines

et al. 2021

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“…COVID-19 mRNA vaccination has been actively implemented globally. It has been effective in inducing serum antibody responses and protect against SARS-CoV-2 infection in clinical and animal studies [ 35 , 36 , 37 ]. In our aged mice model, their serum-neutralizing antibody titre was significantly lower than that of the vaccinated young mice, with 2 of 6 aged mice having no detectable neutralizing antibody titre after two-dose vaccination.…”

Section: Discussionmentioning

confidence: 99%

Age-associated SARS-CoV-2 breakthrough infection and changes in immune response in a mouse model

Chen

Liu

et al. 2022

Emerging Microbes & Infections

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Older individuals are at higher risk of SARS-CoV-2 infection and severe outcomes, but the underlying mechanisms are incompletely understood. In addition, how age modulates SARS-CoV-2 re-infection and vaccine breakthrough infections remain largely unexplored. Here, we investigated age-associated SARS-CoV-2 pathogenesis, immune responses, and the occurrence of re-infection and vaccine breakthrough infection utilizing a wild-type C57BL/6N mouse model. We demonstrated that interferon and adaptive antibody response upon SARS-CoV-2 challenge are significantly impaired in aged mice compared to young mice, which results in more effective virus replications and severe disease manifestations in the respiratory tract. Aged mice also showed increased susceptibility to re-infection due to insufficient immune protection acquired during the primary infection. Importantly, two-dose COVID-19 mRNA vaccination conferred limited adaptive immune response among the aged mice, making them susceptible to SARS-CoV-2 infection. Collectively, our findings call for tailored and optimized treatments and prevention strategies against SARS-CoV-2 among older individuals.

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“…SARS-CoV-2 mRNA-based vaccines induce a robust GC and T FH cell response in mice 93 , 94 . However, the role of the GC response in the human B cell response to vaccination was until recently unclear owing to an inability to directly sample draining lymph nodes following vaccination.…”

Section: B Cell Response To Sars-cov-2 Vaccinationmentioning

confidence: 99%

The germinal centre B cell response to SARS-CoV-2

2021

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The germinal centre (GC) response is critical for the generation of affinity-matured plasma cells and memory B cells capable of mediating long-term protective immunity. Understanding whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or vaccination elicits a GC response has profound implications for the capacity of responding B cells to contribute to protection against infection. However, direct assessment of the GC response in humans remains a major challenge. Here we summarize emerging evidence for the importance of the GC response in the establishment of durable and broad immunity against SARS-CoV-2 and discuss new approaches to modulate the GC response to better protect against newly emerging SARS-CoV-2 variants. We also discuss new findings showing that the GC B cell response persists in the draining lymph nodes for at least 6 months in some individuals following vaccination with SARS-CoV-2 mRNA-based vaccines.

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COVID-19 vaccine mRNA-1273 elicits a protective immune profile in mice that is not associated with vaccine-enhanced disease upon SARS-CoV-2 challenge

Cited by 79 publications

References 67 publications

An Established Th2-Oriented Response to an Alum-Adjuvanted SARS-CoV-2 Subunit Vaccine Is Not Reversible by Sequential Immunization with Nucleic Acid-Adjuvanted Th1-Oriented Subunit Vaccines

An Established Th2-Oriented Response to an Alum-Adjuvanted SARS-CoV-2 Subunit Vaccine Is Not Reversible by Sequential Immunization with Nucleic Acid-Adjuvanted Th1-Oriented Subunit Vaccines

Age-associated SARS-CoV-2 breakthrough infection and changes in immune response in a mouse model

The germinal centre B cell response to SARS-CoV-2

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