ChAdOx1 nCoV-19 (AZD1222) vaccine elicits monoclonal antibodies with potent cross-neutralizing activity against SARS-CoV-2 viral variants

Seow, J.; Graham, C.; Hallett, S. R.; Lechmere, T.; Maguire, T. J. A.; Huettner, I.; Cox, D.; Roberts, R.; Waters, A.; Ward, C. C.; Mant, C.; Pitcher, M. J.; Spencer, J.; Fox, J.; Malim, M. H.; Doores, K. J.

doi:10.1101/2021.09.27.461862

bioRxiv · 10.1101/2021.09.27.461862

ChAdOx1 nCoV-19 (AZD1222) vaccine elicits monoclonal antibodies with potent cross-neutralizing activity against SARS-CoV-2 viral variants

Seow, J.·Graham, C.·Hallett, S. R.·Lechmere, T.·Maguire, T. J. A.·Huettner, I.·Cox, D.·Roberts, R.·Waters, A.·Ward, C. C.·Mant, C.·Pitcher, M. J.·Spencer, J.·Fox, J.·Malim, M. H.·Doores, K. J.

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Abstract

Although the antibody response to COVID-19 vaccination has been studied extensively at the polyclonal level using immune sera, little has been reported on the antibody response at the monoclonal level. Here we isolate a panel of 44 anti-SARS-CoV-2 monoclonal antibodies (mAbs) from an individual who received two doses of the ChAdOx1 nCoV-19 (AZD1222) vaccine at a 12-week interval. We show that despite a relatively low serum neutralization titre, mAbs with potent neutralizing activity against the current SARS-CoV-2 variants of concern (B.1.1.7, P.1, B.1.351 and B.1.617.2) were obtained. The vaccine elicited neutralizing mAbs form 8 distinct competition groups and bind epitopes overlapping with neutralizing mAbs elicited following SARS-CoV-2 infection. AZD1222 elicited mAbs are more mutated than mAbs isolated from convalescent donors 1-2 months post infection. Spike reactive IgG+ B cells were still detectable 9-months post boost. These findings give molecular insights into AZD1222 elicited antibody response.

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Seow, J., Graham, C., Hallett, S. R., Lechmere, T., Maguire, T. J. A., Huettner, I., Cox, D., Roberts, R., Waters, A., Ward, C. C., Mant, C., Pitcher, M. J., Spencer, J., Fox, J., Malim, M. H., Doores, K. J.. 2021-09-28. ChAdOx1 nCoV-19 (AZD1222) vaccine elicits monoclonal antibodies with potent cross-neutralizing activity against SARS-CoV-2 viral variants. https://doi.org/10.1101/2021.09.27.461862

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