A single mRNA immunization boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection

Stamatatos, Leonidas; Czartoski, Julie; Wan, Yu-Hsin; Homad, Leah J.; Rubin, Vanessa; Glantz, Hayley; Neradilek, Moni B.; Seydoux, Emilie; Jennewein, Madeleine F.; MacCamy, Anna J.; Feng, Junli; Mize, Gregory J.; Rosa, Stephen C. De; Finzi, Andrés; Lemos, Maria P.; Cohen, Kristen W.; Moodie, Zoe; McElrath, M. Juliana; McGuire, Andrew T.

doi:10.1101/2021.02.05.21251182

Cited by 95 publications

(46 citation statements)

References 94 publications

(82 reference statements)

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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%

“…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. Moreover, how antibody levels predict or relate to memory B cell responses following mRNA vaccination remains to be determined.…”

Section: Introductionmentioning

confidence: 99%

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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: 99%

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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“…We observed no neutralizing activity in plasma from vaccinated SARS-CoV-2 naïve individuals (Figure 3A), in agreement with previous findings 38 . As recently described 22, 57 , we observed that pre-existing SARS-CoV-2 neutralizing antibody responses were significantly boosted by a single dose of Spike-encoded mRNA vaccine (Figure 3A). Interestingly, a single dose enlarged the potency of the neutralizing response that was now able to efficiently neutralize pseudoviral particles bearing the B.1.1.7 Spike or from other variants with different concerning mutations (E484K, S477N, N501Y, N501S) (Figure S2E-G).…”

Section: Resultssupporting

confidence: 84%

“…The E484K mutation, is part of the South African B.1.351 variant and is now found in several SARS-CoV-2 genomes worldwide that spread rapidly 17 . Studies have shown that this mutation increases affinity of the S glycoprotein for ACE-2 18 and confers resistance to neutralization mediated by mAbs and plasma from naturally-infected and vaccinated individuals 19–22 . The S477N mutation confers a higher affinity for the ACE-2 receptor and has rapidly spread to many countries in Oceania and Europe 23–28 .…”

Section: Introductionmentioning

confidence: 99%

A single BNT162b2 mRNA dose elicits antibodies with Fc-mediated effector functions and boost pre-existing humoral and T cell responses

Tauzin

Nayrac

Benlarbi

et al. 2021

Preprint

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The standard dosing of the Pfizer/BioNTech BNT162b2 mRNA vaccine validated in clinical trials includes two doses administered three weeks apart. While the decision by some public health authorities to space the doses because of limiting supply has raised concerns about vaccine efficacy, data indicate that a single dose is up to 90% effective starting 14 days after its administration. We analyzed humoral and T cells responses three weeks after a single dose of this mRNA vaccine. Despite the proven efficacy of the vaccine at this time point, no neutralizing activity were elicited in SARS-CoV-2 naïve individuals. However, we detected strong anti-receptor binding domain (RBD) and Spike antibodies with Fc-mediated effector functions and cellular responses dominated by the CD4+ T cell component. A single dose of this mRNA vaccine to individuals previously infected by SARS-CoV-2 boosted all humoral and T cell responses measured, with strong correlations between T helper and antibody immunity. Neutralizing responses were increased in both potency and breadth, with distinctive capacity to neutralize emerging variant strains. Our results highlight the importance of vaccinating uninfected and previously-infected individuals and shed new light into the potential role of Fc-mediated effector functions and T cell responses in vaccine efficacy. They also provide support to spacing the doses of two-vaccine regimens to vaccinate a larger pool of the population in the context of vaccine scarcity against SARS-CoV-2.

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“…All of these mutations are located in the receptor binding site (RBS) of the receptor binding domain (RBD) of the spike (S) protein (Figure 1A). Two of these three mutations, K417N and E484K, decrease the neutralizing activity of sera as well as of monoclonal antibodies isolated from COVID-19 convalescent plasma and vaccinated individuals ( 4–10 ). Previous studies have shown that certain IGHV genes are highly enriched in the antibody response to SARS-CoV-2 infection, especially IGHV3-53 ( 11–15 ) and IGHV1-2 ( 12, 16, 17 ).…”

Section: Introductionmentioning

confidence: 99%

Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants

Yuan

Huang

Lee

et al. 2021

Preprint

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The protective efficacy of neutralizing antibodies (nAbs) elicited during natural infection with SARS-CoV-2 and by vaccination based on its spike protein has been compromised with emergence of the recent SARS-CoV-2 variants. Residues E484 and K417 in the receptor-binding site (RBS) are both mutated in lineages first described in South Africa (B.1.351) and Brazil (B.1.1.28.1). The nAbs isolated from SARS-CoV-2 patients are preferentially encoded by certain heavy-chain germline genes and the two most frequently elicited antibody families (IGHV3-53/3-66 and IGHV1-2) can each bind the RBS in two different binding modes. However, their binding and neutralization are abrogated by either the E484K or K417N mutation, whereas nAbs to the cross-reactive CR3022 and S309 sites are largely unaffected. This structural and functional analysis illustrates why mutations at E484 and K417 adversely affect major classes of nAbs to SARS-CoV-2 with consequences for next-generation COVID-19 vaccines.

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A single mRNA immunization boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection

Cited by 95 publications

References 94 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

A single BNT162b2 mRNA dose elicits antibodies with Fc-mediated effector functions and boost pre-existing humoral and T cell responses

Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants

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