包含祖先武汉-Hu-1(WH1)和OmicronBA.1或BA.5亚变体的二价COVID-19疫苗引起对新出现的Omicron亚变体的血清抗体反应增强。这里,我们用BA.1或BA.5二价疫苗第四剂后表征了RBD特异性记忆B细胞(Bmem)反应,与WH1单价第四剂直接比较。先前用mRNA或腺病毒载体单价疫苗免疫的医护人员在用单价或BA.1或BA.5二价疫苗第四次剂量之前和之后一个月取样。定量血清中和抗体(NAb),以及RBD特异性Bmem,具有深入的光谱流式细胞术面板,包括WH1,BA.1,BA.5,BQ.1.1和XBB.1.5变体的重组RBD蛋白。与单价疫苗相比,两种二价疫苗均引发针对Omicron亚变体的更高NAb滴度。在任何一种疫苗类型之后,受者WH1RBD特异性Bmem数量略有增加.两种二价疫苗均显着增加了通过流式细胞术测试的所有Omicron亚变体的WH1RBD特异性Bmem结合,而单价接种后对Omicron亚变体的识别没有增强。IgG1+Bmem主导了反应,与大量的IgG4+Bmem仅在其主要剂量的mRNA疫苗的接受者中检测到。因此,基于Omicron的二价疫苗可以显着增强针对祖先WH1和Omicron变体的NAb和Bmem特异性,并通过预先存在的改进对后代亚变体的识别,特定于WH1的Bmem,超越传统,单价疫苗。这为基于变体的mRNA加强疫苗改善针对新出现的SARS-CoV-2变体的免疫记忆并可能预防严重疾病的能力提供了新的见解。一句总结:OmicronBA.1和BA.5二价COVID-19助推器,用作第四剂,增加Omicron亚变体的RBD特异性Bmem交叉识别,由疫苗和抗原上不同的亚变体编码的那些,比单价助推器还多。
Bivalent COVID-19 vaccines comprising ancestral Wuhan-Hu-1 (WH1) and the Omicron BA.1 or BA.5 subvariant elicit enhanced serum antibody responses to emerging Omicron subvariants. Here, we characterized the RBD-specific memory B cell (Bmem) response following a fourth dose with a BA.1 or BA.5 bivalent vaccine, in direct comparison with a WH1 monovalent fourth dose. Healthcare workers previously immunized with mRNA or adenoviral vector monovalent vaccines were sampled before and one month after a fourth dose with a monovalent or a BA.1 or BA.5 bivalent vaccine. Serum neutralizing antibodies (NAb) were quantified, as well as RBD-specific Bmem with an in-depth spectral flow cytometry panel including recombinant RBD proteins of the WH1, BA.1, BA.5, BQ.1.1, and XBB.1.5 variants. Both bivalent vaccines elicited higher NAb titers against Omicron subvariants compared to the monovalent vaccine. Following either vaccine type, recipients had slightly increased WH1 RBD-specific Bmem numbers. Both bivalent vaccines significantly increased WH1 RBD-specific Bmem binding of all Omicron subvariants tested by flow cytometry, while recognition of Omicron subvariants was not enhanced following monovalent vaccination. IgG1+ Bmem dominated the response, with substantial IgG4+ Bmem only detected in recipients of an mRNA vaccine for their primary dose. Thus, Omicron-based bivalent vaccines can significantly boost NAb and Bmem specific for ancestral WH1 and Omicron variants and improve recognition of descendent subvariants by pre-existing, WH1-specific Bmem beyond that of a monovalent vaccine. This provides new insights into the capacity of variant-based mRNA booster vaccines to improve immune memory against emerging SARS-CoV-2 variants and potentially protect against severe disease. ONE-SENTENCE SUMMARY: Omicron BA.1 and BA.5 bivalent COVID-19 boosters, used as a fourth dose, increase RBD-specific Bmem cross-recognition of Omicron subvariants, both those encoded by the vaccines and antigenically distinct subvariants, further than a monovalent booster.