Maternal Antibody Improves Active Neonatal Vaccination against Respiratory Syncytial Virus through Immune Complex

Abstract

Respiratory syncytial virus (RSV) is a common infectious pathogen in infants. Vaccination is an important approach in the prevention of RSV infection in early age, but early vaccination is limited by low systemic and cellular immune responses. To overcome this difficulty, we in this study explored a novel vaccination strategy in a mouse model. Pregnant mother was vaccinated at day 14 of gestation and offspring were actively vaccinated at day 3 after birth. We observed a high level of maternal anti-RSV antibody in offspring born to the RSV immunized mother, but it declined 6 weeks after birth. However, anti-RSV antibody was low in offspring received active immunization alone. After offspring were nasal challenged with 2.8 × 10 5 i.u. RSV at age of 6 weeks old, we observed significant low levels of lung RSV load and inflammation in offspring received both passive and active vaccination as compared to the offspring received passive or active vaccination alone. The increased protection was associated with the increased endogenous production of anti-RSV antibody and Th1-biased cytokine IFN-gamma. Further in vitro study confirmed that maternal anti-RSV antibody and RSV antigen formed immune complex. The splenocytes stimulated with RSV immune complex expressed higher level of IFN-gamma than those stimulated with RSV alone. Thus, maternal anti-RSV antibody increased efficacy of active vaccination in neonates as early as 3 days after birth and provided more protection against RSV than passive or active vaccination alone. Formation of RSV immune complex in respiratory mucusal tissues may contribute to the improved Th1-biased immune responses.