No substantial preexisting B cell immunity against SARS-CoV-2 in healthy adults

Ercanoglu, Meryem S.; Gieselmann, Lutz; Sabrina, Dähling; Poopalasingam, Nareshkumar; Detmer, Susanne; Koch, Manuel; Korenkov, Michael; Halwe, Sandro; Klüver, Michael; Cristanziano, Veronica Di; Janicki, Hanna; Schlotz, Maike; Worczinski, Johanna; Gathof, Birgit; Gruell, Henning; Zehner, Matthias; Becker, Stephan; Vanshylla, Kanika; Kreer, Christoph; Klein, Florian

doi:10.1016/j.isci.2022.103951

Cited by 8 publications

(4 citation statements)

References 80 publications

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“…There was no difference in the extent of B and T cell responses between vaccinated individuals and healthy donors (Figures 2B, 3A). Our data are consistent with the presence of cross-reactive B cells against the non-RBD portions of Omicron in unvaccinated uninfected individuals (62) with no preexisting B cell immunity against the spike protein of SARS-CoV-2 of the Wuhan Hu-1 variant (63). As for memory B cells, there were no differences in terms of either the frequency or phenotype of CD27 + B cells between previously infected and infection-naïve subjects (Figure 2C).…”

Section: Resultssupporting

confidence: 86%

Long-term adaptive response in COVID-19 vaccine recipients and the effect of a booster dose

Perico

Todeschini²,

Casiraghi³

et al. 2023

Front. Immunol.

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We examined the immune response in subjects previously infected with SARS-CoV2 and infection-naïve 9 months after primary 2-dose COVID-19 mRNA vaccination and 3 months after the booster dose in a longitudinal cohort of healthcare workers. Nine months after primary vaccination, previously infected subjects exhibited higher residual antibody levels, with significant neutralizing activity against distinct variants compared to infection-naïve subjects. The higher humoral response was associated with higher levels of receptor binding domain (RBD)-specific IgG+ and IgA+ memory B cells. The booster dose increased neither neutralizing activity, nor the B and T cell frequencies. Conversely, infection-naïve subjects needed the booster to achieve comparable levels of neutralizing antibodies as those found in previously infected subjects after primary vaccination. The neutralizing titer correlated with anti-RBD IFNγ producing T cells, in the face of sustained B cell response. Notably, pre-pandemic samples showed high Omicron cross-reactivity. These data show the importance of the booster dose in reinforcing immunological memory and increasing circulating antibodies in infection-naïve subjects.

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Section: Resultssupporting

confidence: 86%

Long-term adaptive response in COVID-19 vaccine recipients and the effect of a booster dose

Perico

Todeschini²,

Casiraghi³

et al. 2023

Front. Immunol.

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“…Given the high prevalence of immunity to endemic betacoronaviruses (e.g., HCoV-OC43), it was speculated whether B cell reactivity to SARS-CoV-2 may preexist in naive individuals and shape immunological outcomes of infec-tion. Although SARS-CoV-2 binding antibodies could be observed in rare cases (Anderson et al, 2021;Ng et al, 2020) and monoclonal antibodies with low neutralizing activity have been reported in seronegative individuals (Feldman et al, 2021), SARS-CoV-2 neutralizing activity was mostly undetectable in prepandemic samples (Ercanoglu et al, 2022;Poston et al, 2021). However, upon exposure to SARS-CoV-2 antigen, activation of preexisting betacoronavirus-reactive B cells could be detected but was not associated with protection from SARS-CoV-2 infection (Anderson et al, 2021;Sokal et al, 2021;Song et al, 2021;Turner et al, 2021b).…”

Section: Development Of Sars-cov-2 Neutralizing Antibodiesmentioning

confidence: 98%

Antibody-mediated neutralization of SARS-CoV-2

et al. 2022

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“…77,78 However, none of the wild-type or germline variant antibodies showed any reactivity against OC43, HKU1, NL63, or 229E spike proteins, supporting previous studies that found only little or no recall from memory HCoV responses. 79,80 In the context of other pathogens including HIV-1, HCV, or RSV, it has been shown that antibodies carry mutations that are neglectable for binding or neutralization. [14][15][16] Concordantly, we identified a fraction of mutated anti-SARS-CoV-2 antibodies (~11%) that bound and neutralized Wu01 independently of acquired mutations, at least within the resolution of our assays.…”

Section: Discussionmentioning

confidence: 99%

Dissecting the impact of somatic hypermutation on SARS-CoV-2 neutralization and viral escape

Korenkov,

Zehner,

Cohen-Dvashi

et al. 2023

Preprint

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Somatic hypermutation (SHM) drives affinity maturation and continues over months in SARS-CoV-2 neutralizing antibodies. Yet, several potent SARS-CoV-2 antibodies carry no or only few mutations, leaving the question of how ongoing SHM affects neutralization. Here, we reverted variable region mutations of 92 antibodies and tested their impact on SARS-CoV-2 binding and neutralization. Reverting higher numbers of mutations correlated with decreasing antibody functionality. However, some antibodies, including the public clonotype VH1-58, remained unaffected for Wu01 activity. Moreover, while mutations were dispensable for Wu01-induced VH1-58 antibodies to neutralize Alpha, Beta, and Delta variants, they were critical to neutralize Omicron BA.1/BA.2. Notably, we exploited this knowledge to convert the clinical antibody tixagevimab into a BA.1/BA.2-neutralizer. These findings substantially broaden our understanding of SHM as a mechanism that not only improves antibody responses during affinity maturation, but also counteracts antigenic imprinting through antibody diversification and thus increases the chances of neutralizing viral escape variants.

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No substantial preexisting B cell immunity against SARS-CoV-2 in healthy adults

Cited by 8 publications

References 80 publications

Long-term adaptive response in COVID-19 vaccine recipients and the effect of a booster dose

Long-term adaptive response in COVID-19 vaccine recipients and the effect of a booster dose

Antibody-mediated neutralization of SARS-CoV-2

Dissecting the impact of somatic hypermutation on SARS-CoV-2 neutralization and viral escape

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