RT Journal Article
SR Electronic
T1 Heterotypic vaccination responses against SARS-CoV-2 Omicron BA.2
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.03.22.485418
DO 10.1101/2022.03.22.485418
A1 Zhenhao Fang
A1 Lei Peng
A1 Qianqian Lin
A1 Liqun Zhou
A1 Luojia Yang
A1 Yanzhi Feng
A1 Ping Ren
A1 Paul A. Renauer
A1 Jonathan J. Park
A1 Xiaoyu Zhou
A1 Craig B. Wilen
A1 Sidi Chen
YR 2022
UL http://biorxiv.org/content/early/2022/03/23/2022.03.22.485418.abstract
AB The Omicron sub-lineage BA.2 of SARS-CoV-2 has recently become dominant across many areas in the world in the on-going waves of COVID-19. Compared to the ancestral/wild-type (WT) virus, Omicron lineage variants, both BA.1 and BA.2, contain high number of mutations, especially in the spike protein, causing significant immune escape that leads to substantial reduction of vaccine and antibody efficacy. Because of this antigenic drift, BA.2 exhibited differential resistance profile to monoclonal antibodies than BA.1. Thus, it is important to understand whether the immunity elicited by currently available vaccines are effective against the BA.2 subvariant. We directly tested the heterotypic vaccination responses against Omicron BA.2, using vaccinated serum from animals receiving WT- and variant-specific mRNA vaccine in lipid nanoparticle (LNP) formulations. Omicron BA.1 and BA.2 antigen showed similar reactivity to serum antibodies elicited by two doses of WT, B.1.351 and B.1.617 LNP-mRNAs. Neutralizing antibody titers of B.1.351 and B.1.617 LNP-mRNA were ~2-fold higher than that of WT LNP-mRNA. Both homologous boosting with WT LNP-mRNA and heterologous boosting with BA.1 LNP-mRNA substantially increased waning immunity of WT vaccinated mice against both BA.1 and BA.2 subvariants. The BA.1 LNP-mRNA booster was ~3-fold more efficient than WT LNP-mRNA at elevating neutralizing antibody titers of BA.2. Together, these data provided a direct preclinical evaluation of WT and variant-specific LNP-mRNAs in standard two-dose and as boosters against BA.1 and BA.2 subvariants.Competing Interest StatementThe authors have declared no competing interest.