Ipsilateral or contralateral boosting of mice with mRNA vaccines confers equivalent immunity and protection against a SARS-CoV-2 Omicron strain.

Autor:	Ying B; Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA., Liang C-Y; Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA., Desai P; Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA., Scheaffer SM; Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA., Elbashir SM; Moderna, Inc., Cambridge, Massachusetts, USA., Edwards DK; Moderna, Inc., Cambridge, Massachusetts, USA., Thackray LB; Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA., Diamond MS; Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA.; The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, Missouri, USA.; Center for Vaccines and Immunity to Microbial Pathogens, Washington University School of Medicine, St. Louis, Missouri, USA.
Jazyk:	angličtina
Zdroj:	Journal of virology [J Virol] 2024 Sep 17; Vol. 98 (9), pp. e0057424. Date of Electronic Publication: 2024 Aug 28.
DOI:	10.1128/jvi.00574-24
Abstrakt:	Boosting with mRNA vaccines encoding variant-matched spike proteins has been implemented to mitigate their reduced efficacy against emerging SARS-CoV-2 variants. Nonetheless, in humans, it remains unclear whether boosting in the ipsilateral or contralateral arm with respect to the priming doses impacts immunity and protection. Here, we boosted K18-hACE2 mice with either monovalent mRNA-1273 (Wuhan-1 spike) or bivalent mRNA-1273.214 (Wuhan-1 + BA.1 spike) vaccine in the ipsilateral or contralateral leg after a two-dose priming series with mRNA-1273. Boosting in the ipsilateral or contralateral leg elicited equivalent levels of serum IgG and neutralizing antibody responses against Wuhan-1 and BA.1. While contralateral boosting with mRNA vaccines resulted in the expansion of spike-specific B and T cells beyond the ipsilateral draining lymph node (DLN) to the contralateral DLN, administration of a third mRNA vaccine dose at either site resulted in similar levels of antigen-specific germinal center B cells, plasmablasts/plasma cells, T follicular helper cells, and CD8 + T cells in the DLNs and the spleen. Furthermore, ipsilateral and contralateral boosting with mRNA-1273 or mRNA-1273.214 vaccines conferred similar homologous or heterologous immune protection against SARS-CoV-2 BA.1 virus challenge with equivalent reductions in viral RNA and infectious virus in the nasal turbinates and lungs. Collectively, our data show limited differences in B and T cell immune responses after ipsilateral and contralateral site boosting by mRNA vaccines that do not substantively impact protection against an Omicron strain.IMPORTANCESequential boosting with mRNA vaccines has been an effective strategy to overcome waning immunity and neutralization escape by emerging SARS-CoV-2 variants. However, it remains unclear how the site of boosting relative to the primary vaccination series shapes optimal immune responses or breadth of protection against variants. In K18-hACE2 transgenic mice, we observed that intramuscular boosting with historical monovalent or variant-matched bivalent vaccines in the ipsilateral or contralateral limb elicited comparable levels of serum spike-specific antibody and antigen-specific B and T cell responses. Moreover, boosting on either side conferred equivalent protection against a SARS-CoV-2 Omicron challenge strain. Our data in mice suggest that the site of intramuscular boosting with an mRNA vaccine does not substantially impact immunity or protection against SARS-CoV-2 infection. Competing Interests: M.S.D. is a consultant or advisor for Inbios, Vir Biotechnology, IntegerBio, Moderna, Merck, GlaxoSmithKline, and Marshall, Gerstein and Borun. The Diamond laboratory has received unrelated funding support in sponsored research agreements from Vir Biotechnology, Emergent BioSolutions, and IntegerBio. S.M.E. and D.K.E. are employees and shareholders in Moderna Inc. All other authors declare no conflicts of interest.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu