The distinct impact of maternal antibodies on the immunogenicity of live and recombinant rotavirus vaccines

Abstract

A high titre of maternal antibodies is one of the possible factors associated with decreased rotavirus vaccine efficacy in low-income countries where rotavirus-associated morbidity and mortality are high. Although some studies show a negative correlation between maternal antibody levels and seroconversion after vaccination, withholding breastfeeding does not improve rotavirus vaccine efficacy. Different types of recombined vaccines were developed as an alternative to produce higher protection in developing areas. In previous studies, we found that recombinantly expressed, truncated VP4* can stimulate high titres of neutralizing antibodies and can confer protection against rotavirus infections and rotavirus-induced diarrhoea. In this study, the impact of maternal antibodies on live and recombinant rotavirus vaccines (VP4*) was evaluated in a mouse model. Dams were infected orally with murine rotavirus 7 days after delivery to mimic a natural rotavirus infection in infants and to evaluate the separate effects of trans-placentally acquired and milk-acquired maternal antibodies, pups were half exchanged. After immunization with live rotavirus, both the neutralizing antibody and IgA antibody responses were inhibited by maternal antibodies, especially by milk antibodies; however, the neutralizing antibody responses after immunization with recombinant VP4* were enhanced. In addition, the in vitro incubation of VP4* with immune sera of rotavirus could also enhance the immune responses could also enhance the immune responses. Our finding provides a basis for the development of non-replicating vaccines to address the problem of live attenuated vaccines in low- and middle-income countries.