Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals after mRNA vaccination

Goel, Rishi R.; Apostolidis, Sokratis A.; Painter, Mark M.; Mathew, Divij; Pattekar, Ajinkya; Kuthuru, Oliva; Gouma, Sigrid; Hicks, Philip; Meng, Wenzhao; Rosenfeld, Aaron M.; Dysinger, Sarah; Lundgreen, Kendall A.; Kuri-Cervantes, Leticia; Adamski, Sharon; Hicks, Amanda; Korte, Scott; Oldridge, Derek A.; Baxter, Amy E.; Giles, Josephine R.; Weirick, Madison E.; McAllister, Christopher M.; Dougherty, Jeanette; Long, Sherea; D’Andrea, Kurt; Hamilton, Jacob T.; Betts, Michael R.; Prak, Eline T. Luning; Bates, Paul; Hensley, Scott E.; Greenplate, Allison R.; Wherry, E. John

doi:10.1126/sciimmunol.abi6950

Cited by 613 publications

(716 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%

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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%

“…These titers are an order of magnitude higher than the neutralizing titers achieved against the wild-type SARS-CoV-2 at the peak of the initial response in infected individuals and in naïve individuals receiving both doses of mRNA vaccines (Fig. 1d and 2,[5][6][7][8] ).…”

mentioning

confidence: 99%

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

Wang

Muecksch

Schaefer-Babajew

et al. 2021

Preprint

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“…Our study on specific T cells has some limitations: (1) the sample size for which in-depth T-cell profiling was performed was limited to 20 donors; (2) we only focused on S-specific T cells; and (3) we were not able to further address CD8 + T-cell responses to VOC, due to low frequency of SARS-CoV-2-specific CD8 + T cells. Although we hypothesize this was due to minimal disease severity in this HCW cohort (40,41), alternatively this could be because of limited sensitivity when using peptide pools containing overlapping 15mers. Additional studies with smaller peptides (8-10mers) predicted or shown to bind HLA class I are advised to specifically study VOC cross-reactive CD8 + T-cell responses.…”

Section: Discussionmentioning

confidence: 92%

“…Previously, we regarded individuals with a SI > 3 as responders, however this was in an intensive care unit (ICU) cohort with strong T-cell responses (11). Since the strength of the Tcell response seems to be correlated to disease severity (40,41), we lowered the arbitrary cut-off to an SI > 2 to identify responders after mild COVID-19 (Table S1). In COVID-19 naive donors, CD4 + T-cell responders were not observed prevaccination, whereas 5 out of 7 responders were identified after 1 or 2 vaccinations.…”

Section: Rapid Boosting Of S-specific T Cells In Covid-19 Recovered Donorsmentioning

confidence: 99%

SARS-CoV-2 variants of concern partially escape humoral but not T cell responses in COVID-19 convalescent donors and vaccine recipients

et al. 2021

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The emergence of SARS-CoV-2 variants harboring mutations in the spike (S) protein has raised concern about potential immune escape. Here, we studied humoral and cellular immune responses to wild type SARS-CoV-2 and the B.1.1.7 and B.1.351 variants of concern in a cohort of 121 BNT162b2 mRNA-vaccinated health care workers (HCW). Twenty-three HCW recovered from mild COVID-19 disease and exhibited a recall response with high levels of SARS-CoV-2-specific functional antibodies and virus-specific T cells after a single vaccination. Specific immune responses were also detected in seronegative HCW after one vaccination, but a second dose was required to reach high levels of functional antibodies and cellular immune responses in all individuals. Vaccination-induced antibodies cross-neutralized the variants B.1.1.7 and B.1.351, but the neutralizing capacity and Fc-mediated functionality against B.1.351 was consistently 2- to 4-fold lower than to the homologous virus. In addition, peripheral blood mononuclear cells were stimulated with peptide pools spanning the mutated S regions of B.1.1.7 and B.1.351 to detect cross-reactivity of SARS-CoV-2-specific T cells with variants. Importantly, we observed no differences in CD4+ T-cell activation in response to variant antigens, indicating that the B.1.1.7 and B.1.351 S proteins do not escape T-cell-mediated immunity elicited by the wild type S protein. In conclusion, this study shows that some variants can partially escape humoral immunity induced by SARS-CoV-2 infection or BNT162b2 vaccination, but S-specific CD4+ T-cell activation is not affected by the mutations in the B.1.1.7 and B.1.351 variants.

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“…Analogous results were reported in a recent study by Goel et al, demonstrating the amplification of neutralizing titers against D614G and B.1.351 pseudoviruses in individuals with prior infection after a single dose of mRNA vaccine, with little improvement observed after dose two. 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.…”

mentioning

confidence: 96%