オミクロン変異株BA.5とワクチン・抗体

BA.5に対するワクチンの効果や抗体に関して

The effect of Omicron breakthrough infection and extended BNT162b2 booster dosing on neutralization breadth against SARS–CoV–2 variants of concern
【medRxiv 2022年8月5日】

Abstract

COVID–19 vaccines are playing a vital role in controlling the COVID–19 pandemic. As SARS–CoV–2 variants encoding mutations in the surface glycoprotein, Spike, continue to emerge, there is increased need to identify immunogens and vaccination regimens that provide the broadest and most durable immune responses. We compared the magnitude and breadth of the neutralizing antibody response, as well as levels of Spike–reactive memory B cells, in individuals receiving a second dose of BNT126b2 at a short (3–4 week) or extended interval (8–12 weeks) and following a third vaccination approximately 6–8 months later. We show that whilst an extended interval between the first two vaccinations can greatly increase the breadth of the immune response and generate a higher proportion of Spike reactive memory B cells, a third vaccination leads to similar levels between the two groups. Furthermore, we show that the third vaccine dose enhances neutralization activity against omicron lineage members BA.1, BA.2 and BA.4/BA.5 and this is further increased following breakthrough infection during the UK omicron wave. These findings are relevant for vaccination strategies in populations where COVID–19 vaccine coverage remains low.

mRNA vaccines and hybrid immunity use different B cell germlines to neutralize Omicron BA.4 and BA.5
【bioRxiv 2022年8月5日】

Abstract

SARS-CoV-2 omicron BA.4 and BA.5, characterized by high transmissibility and ability to escape natural and vaccine induced immunity, are rampaging worldwide. To understand the escape mechanisms, we tested the neutralizing activity against omicron BA.4 and BA.5 of a panel of 482 human monoclonal antibodies that had been isolated from people who received two or three mRNA vaccine doses or from people that had been vaccinated after infection. None of the antibodies isolated after two vaccine doses neutralized omicron BA.4 and BA.5, while these variants were neutralized by approximately 15% of antibodies obtained from people that received three doses or had been vaccinated after infection. Remarkably, the antibodies isolated after three vaccine doses targeted mainly the receptor binding domain (RBD) Class 1/2 epitope region and were encoded by the IGHV1-69 and IGHV3-66 B cell germlines, while the antibodies isolated after infection recognized mostly the RBD Class 3 epitope region and the NTD, and were encoded by the IGHV2-5;IGHJ4-1 and IGHV1-24;IGHJ4-1 germlines. The observation that mRNA vaccination and hybrid immunity elicit a different immunity against the same antigen is intriguing and its understanding may help to design the next generation of therapeutics and vaccines against COVID-19.