Robust immune responses after one dose of BNT162b2 mRNA vaccine dose in SARS-CoV-2 experienced individuals

Samanovic, Marie I.; Cornelius, Amber; Gray-Gaillard, Sophie L.; Allen, Joseph R.; Karmacharya, Trishala; Wilson, Jimmy P.; Hyman, Sara; Tuen, Michael; Koralov, Sergei B.; Mulligan, Mark J.; Herati, Ramin S.

doi:10.1101/2021.02.07.21251311

Cited by 74 publications

(81 citation statements)

References 80 publications

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“…Overall, these data also add to our understanding of SARS-CoV2 mRNA vaccine-induced immune responses in several ways. First, our serological data is consistent with several other recent studies 9,10,12,13,16,17 indicating robust boosting of antibody responses in SARS-CoV2 recovered subjects after the first vaccine dose, but little benefit to antibody titers after the second vaccine dose. Moreover, we identified a similar effect for virus-specific memory B cells, demonstrating that both a quantitative and qualitative plateau in vaccine-induced memory B cells is achieved following the first dose of vaccine with little additional change to the memory B cell response following booster vaccination.…”

Section: Discussionsupporting

confidence: 92%

“…As these individuals have already generated a primary immune response to SARS-CoV2 during their natural infection, it is possible that a single dose of vaccine could be enough to sufficiently boost their antibody and memory B cell responses. Indeed, several recent studies have indicated that antibody responses can be robustly induced in SARS-CoV2 experienced individuals, consistent with an anamnestic response 9–12 . Although one study suggests that memory B cells might also be boosted after a single vaccine dose 13 , it remains unclear how well memory B cell responses are induced in SARS-CoV2 naïve versus SARS-CoV2 experienced subjects after one versus two doses of mRNA vaccine.…”

Section: Introductionmentioning

confidence: 64%

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Longitudinal Analysis Reveals Distinct Antibody and Memory B Cell Responses in SARS-CoV2 Naïve and Recovered Individuals Following mRNA Vaccination

Goel

Apostolidis

Painter

et al. 2021

Preprint

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Novel mRNA vaccines for SARS-CoV2 have been authorized for emergency use and are currently being administered to millions of individuals worldwide. Despite their efficacy in clinical trials, there is limited data on vaccine-induced immune responses in individuals with a prior SARS-CoV2 infection compared to SARS-CoV2 naive subjects. Moreover, how mRNA vaccines impact the development of antibodies as well as memory B cells in COVID-19 experienced versus COVID-19 naive subjects remains poorly understood. In this study, we evaluated antibody responses and antigen-specific memory B cell responses over time in 33 SARS-CoV2 naive and 11 SARS-CoV2 recovered subjects. mRNA vaccination induced significant antibody and memory B cell responses against full-length SARS-CoV2 spike protein and the spike receptor binding domain (RBD). SARS-CoV2 naive individuals benefitted from both doses of mRNA vaccine with additional increases in antibodies and memory B cells following booster immunization. In contrast, SARS-CoV2 recovered individuals had a significant immune response after the first dose with no increase in circulating antibodies or antigen-specific memory B cells after the second dose. Moreover, the magnitude of the memory B cell response induced by vaccination was lower in older individuals, revealing an age-dependence to mRNA vaccine-induced B cell memory. Side effects also tended to associate with post-boost antibody levels, but not with post-boost memory B cells, suggesting that side effect severity may be a surrogate of short-term antibody responses. The frequency of pre-vaccine antigen-specific memory B cells in SARS-CoV2 recovered individuals strongly correlated with post-vaccine antibody levels, supporting a key role for memory B cells in humoral recall responses to SARS-CoV2. This observation may have relevance for future booster vaccines and for responses to viral variants that partially escape pre-existing antibodies and require new humoral responses to be generated from memory B cells. Finally, post-boost antibody levels were not correlated with post-boost memory responses in SARS-CoV2 naive individuals, indicating that short-term antibody levels and memory B cells are complementary immunological endpoints that should be examined in tandem when evaluating vaccine response. Together, our data provide evidence of both serological response and immunological memory following mRNA vaccination that is distinct based on prior SARS-CoV2 exposure. These findings may inform vaccine distribution in a resource-limited setting.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 64%

Longitudinal Analysis Reveals Distinct Antibody and Memory B Cell Responses in SARS-CoV2 Naïve and Recovered Individuals Following mRNA Vaccination

Goel

Apostolidis

Painter

et al. 2021

Preprint

View full text Add to dashboard Cite

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“…More antigen being presented to the immune system does not always equate to higher immunogenicity markers, which appears to be the case between 10 and 30 ug dosing. This is also seen in COVID-19 recovered patients who increase their VNT50 and antibody titres after one dose of vaccination, but not after the second 23 (23). It is also seen in AstraZeneca’s trial data where a low dosing regimen led to equivalent if not greater efficacy than standard dosing 24 (24).…”

Section: Discussionmentioning

confidence: 65%

Low Dose Regimens of BNT162b2 mRNA Vaccine Exceed SARS-Cov-2 Correlate of Protection Estimates for Symptomatic Infection, in those 19-55 Years of Age

G¹

2021

Preprint

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Background: An exact correlate of protection (CoP) is not yet known for symptomatic COVID-19. However, it is still possible to show a new vaccine regimen exceeds an unknown CoP, provided the regimen shows an equivalent or greater immunological response in all measured indicators relative to the immunological response elicited by a clinically proven vaccine regimen. The principle of comparing immunogenicity between regimens is what the FDA, EMA, and Access Consortium use to authorize modifications to the vaccines for VOC, without requiring clinical efficacy studies before implementation. It is logical to apply the same principle to modifying vaccine doses if the data is available to do so. A two dose 30ug regimen of BNT162b2 has strong clinical evidence of efficacy, as does a single dose 30 ug regimen. The immunological markers for these regimens have been profiled in detail in Phase 1 and 2 trial data. Methods: The immunological profile (including binding antibodies, viral neutralization, cytokine profiles, and CD4 and 8 expansion) of the 2 dose 30ug BNT162b2 vaccine is examined, referred to as a highly conservative CoP estimate. The single dose 30 ug BNT162b2 immunological profile is also examined, a tenable CoP estimate. Data from the phase 1 and 2 trials are examined to see if alternate regimens meet or exceed the level of each immune marker measured, relative to the regimens listed above that have proven clinical efficacy. Results: For adults aged 19-55, a 2 dose 10ug BNT162b2 regimen elicits a comparable response to the standard 30 ug dose for each immune indicator, with viral neutralization nearly an order of magnitude greater than the tenable CoP estimate. Similarly, a single dose 10ug BNT 162b2 regimen or a two dose 1ug BNT 162b2 regimen equals or exceeds the immunogenicity of a single 30 ug dose. Conclusion: If it is reasonable for the FDA, EMA, and Access Consortium to approve vaccine modifications without a clinical trial based on immunogenicity data, three alternate low dose regimens were identified that meet the requirements of having comparable immunogenicity relative to a protocol that has proven clinical efficacy. Immediate implementation of these lower dose regimens should be considered as they have major implications in alleviating vaccine supply, as well as improving vaccine side effect profile, and lowering total cost of vaccination.

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“… 9 In the New York City cohort, direct ELISA was used to quantify antibody titres on serum as previously described. 10 Titre of 5000 units or greater was used as the cut-off to determine an adequate response to vaccination. IgG antibodies against the S1 domain of the spike protein of SARS-CoV-2 were tested in Erlangen participants using the commercial ELISA from Euroimmun (Lübeck, Germany) on the EUROIMMUN Analyzer I platform and according to the manufacturer’s protocol.…”

Section: Methodsmentioning

confidence: 99%

Methotrexate hampers immunogenicity to BNT162b2 mRNA COVID-19 vaccine in immune-mediated inflammatory disease

et al. 2021

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Objective To investigate the humoral and cellular immune response to mRNA COVID-19 vaccines in patients with immune-mediated inflammatory diseases (IMIDs) on immunomodulatory treatment.Methods Established patients at NYU Langone Health with IMID (n=51) receiving the BNT162b2 mRNA vaccination were assessed at baseline and after second immunization. Healthy subjects served as controls (n=26). IgG antibody responses to the spike protein were analyzed for humoral response. Cellular immune response to SARS-CoV-2 was further analyzed using high-parameter spectral flow cytometry. A second independent, validation cohort of controls (n=182) and patients with IMID (n=31) from Erlangen, Germany were also analyzed for humoral immune response. ResultsAlthough healthy subjects (n=208) and IMID patients on biologic treatments (mostly on TNF blockers, n=37) demonstrate robust antibody responses (over 90%), those patients with IMID on background methotrexate (n=45) achieve an adequate response in only 62.2% of cases.Similarly, IMID patients do not demonstrate an increase in CD8+ T cell activation after vaccination. ConclusionsIn two independent cohorts of IMID patients, methotrexate, a widely used immunomodulator for the treatment of several IMIDs, adversely affected humoral and cellular immune response to COVID-19 mRNA vaccines. Although precise cut offs for immunogenicity that correlate with vaccine efficacy are yet to be established, our findings suggest that different strategies may need to be explored in patients with IMID taking methotrexate to increase the chances of immunization efficacy against SARS-CoV-2 as has been demonstrated for augmenting immunogenicity to other viral vaccines.

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Robust immune responses after one dose of BNT162b2 mRNA vaccine dose in SARS-CoV-2 experienced individuals

Cited by 74 publications

References 80 publications

Longitudinal Analysis Reveals Distinct Antibody and Memory B Cell Responses in SARS-CoV2 Naïve and Recovered Individuals Following mRNA Vaccination

Longitudinal Analysis Reveals Distinct Antibody and Memory B Cell Responses in SARS-CoV2 Naïve and Recovered Individuals Following mRNA Vaccination

Low Dose Regimens of BNT162b2 mRNA Vaccine Exceed SARS-Cov-2 Correlate of Protection Estimates for Symptomatic Infection, in those 19-55 Years of Age

Methotrexate hampers immunogenicity to BNT162b2 mRNA COVID-19 vaccine in immune-mediated inflammatory disease

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