Maternal Antibodies Induced by a Live Attenuated Vaccine Protect Neonatal Mice from Cytomegalovirus

Overview

Journal NPJ Vaccines

Date 2023 Feb 3

PMID 36737485

Authors

Vu Thuy Khanh Le-Trilling

Andreja Jagnjic

Ilija Brizic

Mareike Eilbrecht

Kerstin Wohlgemuth

Carmen Rozmanic

Alan Herdman

Katja Hoffmann

Astrid M Westendorf

Hartmut Hengel

Stipan Jonjic

Mirko Trilling

Affiliations

Soon will be listed here.

Abstract

Human cytomegalovirus (HCMV) frequently causes congenital infections, resulting in birth defects and developmental disorders. A vaccine is needed, but unavailable. We analyzed the potential of CMV mutants, lacking their STAT2 antagonists to serve as live attenuated vaccine viruses in mice. Infections with attenuated viruses elicited strong ELISA-reactive binding IgG responses and induced neutralizing antibodies as well as antibodies stimulating cellular Fcγ receptors, including the antibody-dependent cellular cytotoxicity (ADCC)-eliciting receptors FcγRIII/CD16 and FcγRIV. Accordingly, vaccinated mice were fully protected against challenge infections. Female mice vaccinated prior to gestation transmitted CMV-specific IgG to their offspring, which protected the progeny from perinatal infections in a mouse model for congenital CMV disease. To define the role of maternal antibodies, female mice either capable or incapable of producing antibodies were vaccinated and subsequently bred to males of the opposite genotype. Challenge infections of the genotypically identical F1 generation revealed the indispensability of maternal antibodies for vaccine-induced protection against cytomegaloviruses.

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