mRNA vaccination boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection

Stamatatos, Leonidas; Czartoski, Julie; Wan, Yu; 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:10.1126/science.abg9175

Cited by 529 publications

(605 citation statements)

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“…2b). In contrast and consistent with previous reports 5,8,15 , convalescent individuals that received mRNA vaccines showed an average 8.6-fold increase in the number of circulating RBD specific memory B cells (Fig. 2b).…”

Section: Memory B Cellssupporting

confidence: 93%

Naturally enhanced neutralizing breadth to SARS-CoV-2 after one year

Wang

Muecksch

Schaefer-Babajew

et al. 2021

Preprint

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Over one year after its inception, the coronavirus disease-2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) remains difficult to control despite the availability of several excellent vaccines. Progress in controlling the pandemic is slowed by the emergence of variants that appear to be more transmissible and more resistant to antibodies. Here we report on a cohort of 63 COVID-19-convalescent individuals assessed at 1.3, 6.2 and 12 months after infection, 41% of whom also received mRNA vaccines. In the absence of vaccination antibody reactivity to the receptor binding domain (RBD) of SARS-CoV-2, neutralizing activity and the number of RBD-specific memory B cells remain relatively stable from 6 to 12 months. Vaccination increases all components of the humoral response, and as expected, results in serum neutralizing activities against variants of concern that are comparable to or greater than neutralizing activity against the original Wuhan Hu-1 achieved by vaccination of naive individuals. The mechanism underlying these broad-based responses involves ongoing antibody somatic mutation, memory B cell clonal turnover, and development of monoclonal antibodies that are exceptionally resistant to SARS-CoV-2 RBD mutations, including those found in variants of concern. In addition, B cell clones expressing broad and potent antibodies are selectively retained in the repertoire over time and expand dramatically after vaccination. The data suggest that immunity in convalescent individuals will be very long lasting and that convalescent individuals who receive available mRNA vaccines will produce antibodies and memory B cells that should be protective against circulating SARS-CoV-2 variants. Should memory responses evolve in a similar manner in vaccinated individuals, additional appropriately timed boosting with available vaccines could cover most circulating variants of concern.

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Section: Memory B Cellssupporting

confidence: 93%

Naturally enhanced neutralizing breadth to SARS-CoV-2 after one year

Wang

Muecksch

Schaefer-Babajew

et al. 2021

Preprint

View full text Add to dashboard Cite

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“…We realized that, although different, the antibody response trend was similar. Indeed, the results reported in this study are similar to others that used different methods to measure the efficacy of the vaccine against variants after about a month [ 4 , 13 , 14 , 15 , 16 ]. However, despite the unquestionable scientific relevance of different methods that may be carried out, a uniformity in reporting absolute titer values in International Standard Units is desirable, in order to avoid diverse interpretations of the antibody trend several months after vaccination.…”

Section: Discussionsupporting

confidence: 84%

Neutralizing Antibody Response of Vaccinees to SARS-CoV-2 Variants

et al. 2021

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Due to their increased transmissibility, three variants of high concern have emerged in the United Kingdom (also known as B.1.1.7 lineage or VOC-202012/01), South Africa (B.1.351 lineage), and Brazil (P1 lineage) with multiple substitutions in the spike protein. Since neutralizing antibodies elicited by vaccination are likely considered as correlates of protection for SARS-CoV-2 infection, it is important to analyze whether vaccinees with mRNA BNT162b2 are equally protected against these emerging SARS-CoV-2 variants. To this aim, we enrolled healthy subjects one month after complete vaccination with Comirnaty and evaluated the neutralizing response against the native Wuhan strain and the emerging B.1.1.7, B.1.351 and P1 lineages, by using the microneutralization assay, currently considered the gold standard test for the evaluation and detection of functional neutralizing antibodies. The most remarkable finding of this study was the significantly lower neutralizing antibody titer against B.1.351 lineage, compared to the wild-type virus. No significant differences were observed with the other two lineages. These findings provide evidence that vaccinated subjects may not be equally protected against all SARS-CoV-2 lineages.

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“…5 Notably, Stamatatos et al also show that B.1.351 neutralizing titers in previously infected vaccinees after a single dose were comparable to or higher than autologous neutralizing titers in previously naïve vaccinees after two doses of mRNA vaccine. 3 This result is significant given that the latter is associated with greater than 90% protective efficacy against COVID-19 in clinical trials. 6,7 These data are supported by research suggesting that repeated or prolonged exposure to antigen promotes the diversification of the neutralizing antibody response and targeting of variable epitopes.…”

mentioning

confidence: 99%

“…2 In a recent report in Science, Stamatatos et al investigate neutralizing antibody responses against B.1.351 strains in the sera of naïve and previously infected recipients of BNT162b2 or mRNA-1273. 3 The B.1.351 lineage encompasses the following spike protein amino acid substitutions: K417N, E484K, and N501Y in the receptor-binding domain (RBD); D614G and frequently A701V in S2; D80A, D215G, and occasionally a 242-244 deletion in the Nterminal domain (NTD). 1,4 In their experiments, the authors assess the susceptibility to neutralization of a pseudovirus expressing B.1.351 spike in comparison to a vaccine-matched Wuhan-Hu-1 pseudovirus.…”

mentioning

confidence: 99%