Mechanisms of innate and adaptive immunity to the Pfizer-BioNTech BNT162b2 vaccine

Li, Chunfeng; Lee, Audrey; Grigoryan, L. A.; Arunachalam, Prabhu S.; Scott, Madeleine; Trisal, Meera; Wimmers, Florian; Sanyal, Mrinmoy; Weidenbacher, Payton A.; Feng, Yupeng; Adamska, Julia Z.; Valore, Erika V.; Wang, Yanli; Verma, Rohit; Reis, Noah; Dunham, Diane; O’Hara, Ruth; Park, Helen; Luo, Wei; Gitlin, Alexander D.; Kim, Peter; Khatri, Purvesh; Nadeau, Kari

doi:10.1038/s41590-022-01163-9

Cited by 220 publications

(245 citation statements)

References 66 publications

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“…Recent studies suggest that IFN-γ production from CD8 + T cells enhances cellular and humoral immune responses following immunization ( 30 , 31 ), and that CD8 + T cells can also promote proper resolution of inflammation ( 32 ). Thus, the induction of CD8 + T cells can improve the efficacy of vaccines beyond just killing viruses.…”

Section: Beneficial Role Of Cd8 + T Cells In Acute...mentioning

confidence: 99%

“…Even new vaccines such as CD8 + T cell-inducing mRNA and adenoviral-vector injectable vaccines do not induce the most protective Trm cell populations at the respiratory barrier sites the virus would invade, and hence do not fully utilize the high protective potential of CD8 + T cells ( 30 ). Induction of Trm cells requires the recruitment of effector T cells that are activated in lymph nodes by specific antigens to the peripheral site.…”

Section: Cd8 + T Cells Function Locally and Their ...mentioning

confidence: 99%

“…The high immunogenicity of mRNA vaccines is exerted via innate type I interferon responses ( 30 ), and it might be a concern that the activation of innate immunity by the vaccine directly causes the attrition of pre-existing memory cells. Attrition can also be potentially induced by cell competition for finite resources among memory cells.…”

Section: Potential Concerns About Repeating Boostersmentioning

confidence: 99%

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Considerations of CD8+ T Cells for Optimized Vaccine Strategies Against Respiratory Viruses

Hirai

Yoshioka

2022

Front. Immunol.

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The primary goal of vaccines that protect against respiratory viruses appears to be the induction of neutralizing antibodies for a long period. Although this goal need not be changed, recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have drawn strong attention to another arm of acquired immunity, CD8+ T cells, which are also called killer T cells. Recent evidence accumulated during the coronavirus disease 2019 (COVID-19) pandemic has revealed that even variants of SARS-CoV-2 that escaped from neutralizing-antibodies that were induced by either infection or vaccination could not escape from CD8+ T cell-mediated immunity. In addition, although traditional vaccine platforms, such as inactivated virus and subunit vaccines, are less efficient in inducing CD8+ T cells, newly introduced platforms for SARS-CoV-2, namely, mRNA and adenoviral vector vaccines, can induce strong CD8+ T cell-mediated immunity in addition to inducing neutralizing antibodies. However, CD8+ T cells function locally and need to be at the site of infection to control it. To fully utilize the protective performance of CD8+ T cells, it would be insufficient to induce only memory cells circulating in blood, using injectable vaccines; mucosal immunization could be required to set up CD8+ T cells for the optimal protection. CD8+ T cells might also contribute to the pathology of the infection, change their function with age and respond differently to booster vaccines in comparison with antibodies. Herein, we overview cutting-edge ideas on CD8+ T cell-mediated immunity that can enable the rational design of vaccines for respiratory viruses.

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Section: Beneficial Role Of Cd8 + T Cells In Acute...mentioning

confidence: 99%

Section: Cd8 + T Cells Function Locally and Their ...mentioning

confidence: 99%

Section: Potential Concerns About Repeating Boostersmentioning

confidence: 99%

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Considerations of CD8+ T Cells for Optimized Vaccine Strategies Against Respiratory Viruses

Hirai

Yoshioka

2022

Front. Immunol.

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“…K18-hACE2 transgenic mice received 20 μL of a low dose 10 monovalent CV2CoV, CV2CoV.351, CV2CoV.617 or bivalent vaccine (CV2CoV.351 and CV2CoV.617) containing a total of 0.5 μg mRNA or NaCl (sham) on Day 0 and Day 28 (Fig. S1).…”

Section: Main Textmentioning

confidence: 99%

Low-dose bivalent mRNA vaccine is highly effective against different SARS-CoV-2 variants in a transgenic mouse model

Corleis

Hoffmann

Rauch

et al. 2022

Preprint

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Combining optimized spike (S) protein-encoding mRNA vaccines to target multiple SARS-CoV-2 variants could improve COVID-19 control. We compared monovalent and bivalent mRNA vaccines encoding B.1.351 (Beta) and/or B.1.617.2 (Delta) SARS-CoV-2 S-protein, primarily in a transgenic mouse model and a Wistar rat model. The low-dose bivalent mRNA vaccine contained half the mRNA of each respective monovalent vaccine, but induced comparable neutralizing antibody titres, enrichment of lung-resident memory CD8+ T cells, specific CD4+ and CD8+ responses, and fully protected transgenic mice from SARS-CoV-2 lethality. The bivalent mRNA vaccine significantly reduced viral replication in both Beta- and Delta-challenged mice. Sera from bivalent mRNA vaccine immunized Wistar rats also contained neutralizing antibodies against the B.1.1.529 (Omicron BA.1) variant. These data suggest that low-dose and fit-for-purpose multivalent mRNA vaccines encoding distinct S-proteins is a feasible approach for increasing the potency of vaccines against emerging and co-circulating SARS-CoV-2 variants.

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“…MDA5 was one of the pattern recognition receptors that was mentioned a few times at the workshop. Bali Pulendran showed that, in mice vaccinated with the Pfizer-BioNTech mRNA COVID-19 vaccine, MDA5 is needed for effective vaccination 45 . This was reinforced by studies by Michael Gale, who showed that MDA5, and not RIG-I, is the important innate immune receptor that responds to SARS-CoV-2 RNA in experiments using cell lines and mice 46 .…”

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confidence: 99%

Considering innate immune responses in SARS-CoV-2 infection and COVID-19

et al. 2022

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During the COVID-19 pandemic, much of the media focus has been on adaptive immunity, particularly antibody levels and memory T cells. However, immunologists have been striving to decipher how SARS-CoV-2 infection impacts our first line of defence, namely the innate immune system. In early 2022, Program staff from the NIAID at the NIH organized a workshop focusing on the innate immune response to SARS-CoV-2 infection and during COVID-19, which was chaired by Ralph Baric, Jenny Ting and John Lambris. Following the meeting, Nature Reviews Immunology invited some of the organizers and speakers to share their thoughts on the key discussion points.

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Mechanisms of innate and adaptive immunity to the Pfizer-BioNTech BNT162b2 vaccine

Cited by 220 publications

References 66 publications

Considerations of CD8+ T Cells for Optimized Vaccine Strategies Against Respiratory Viruses

Considerations of CD8+ T Cells for Optimized Vaccine Strategies Against Respiratory Viruses

Low-dose bivalent mRNA vaccine is highly effective against different SARS-CoV-2 variants in a transgenic mouse model

Considering innate immune responses in SARS-CoV-2 infection and COVID-19

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