Omicron-specific naive B cell maturation alleviates immune imprinting induced by SARS-CoV-2 inactivated vaccine

Yisimayi, A.; Song, W.; Wang, J.; Jian, F.; Yu, Y.; Chen, X.; Xu, Y.; An, R.; Wang, Y.; Sun, H.; Wang, P.; Yu, L.; Shao, F.; Jin, R.; Shen, Z.; Cao, Y.

doi:10.1101/2024.05.13.594034

bioRxiv · 10.1101/2024.05.13.594034

Omicron-specific naive B cell maturation alleviates immune imprinting induced by SARS-CoV-2 inactivated vaccine

Yisimayi, A.·Song, W.·Wang, J.·Jian, F.·Yu, Y.·Chen, X.·Xu, Y.·An, R.·Wang, Y.·Sun, H.·Wang, P.·Yu, L.·Shao, F.·Jin, R.·Shen, Z.·Cao, Y.

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Abstract

SARS-CoV-2 ancestral strain-induced immune imprinting poses great challenges to vaccine updates. Studies showed that repeated Omicron exposures could override immune imprinting induced by inactivated vaccines but not mRNA vaccines, a disparity yet to be understood. Here, we analyzed the underlying mechanism of immune imprinting alleviation in inactivated vaccine (CoronaVac) cohorts. We observed in CoronaVac-vaccinated individuals who experienced BA.5/BF.7 breakthrough infection (BTI), the proportion of Omicron-specific memory B cells (MBCs) substantially increased after an extended period post-Omicron BTI, with their antibodies displaying enhanced somatic hypermutation and neutralizing potency. Consequently, the neutralizing antibody epitope distribution encoded by MBCs post-BA.5/BF.7 BTI after prolonged maturation closely mirrors that in BA.5/BF.7-infected unvaccinated individuals. Together, these results indicate the activation and expansion of Omicron-specific naive B cells generated by first-time Omicron exposure helped to alleviate CoronaVac-induced immune imprinting, and the absence of this process should have caused the persistent immune imprinting seen in mRNA vaccine recipients. HighlightsO_LILongitudinal MBC profiling of CoronaVac-vaccinated individuals following BA.5 BTI C_LIO_LIOmicron-specific MBC proportion rises greatly after extended period post-BA.5 BTI C_LIO_LIOmicron-specific naive B cell maturation reduces ancestral strain immune imprinting C_LI

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Yisimayi, A., Song, W., Wang, J., Jian, F., Yu, Y., Chen, X., Xu, Y., An, R., Wang, Y., Sun, H., Wang, P., Yu, L., Shao, F., Jin, R., Shen, Z., Cao, Y.. 2024-05-14. Omicron-specific naive B cell maturation alleviates immune imprinting induced by SARS-CoV-2 inactivated vaccine. https://doi.org/10.1101/2024.05.13.594034

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