Vaccines against respiratory viral pathogens for use in neonates: opportunities and challenges

Abstract

The first six months of life reflect a time of high susceptibility to severe disease following respiratory virus infection. Although this could be improved significantly by immunization, current vaccines are not approved for use in these very young individuals. This is the result of the combined effects of poor immune responsiveness and safety concerns regarding the use of live attenuated vaccines or potent adjuvants in this population. Vaccines to effectively combat respiratory viral infection ideally would result in robust CD4(+) and CD8(+) T cell responses, as well as high-affinity Ab. Inclusion of TLR agonists or single-cycle viruses is an attractive approach for provision of signals that can act as potent stimulators of dendritic cell maturation, as well as direct activators of T and/or B cells. In this article, I discuss the challenges associated with generation of a robust immune response in neonates and the potential for adjuvants to overcome these obstacles.

Figure 1. Neonates exhibit multiple adaptive immune defects that contribute to poor responses following infection or vaccination

Potent adaptive immune responses are dependent on the capacity of DC to undergo maturation together with the robust activation, differentiation and survival of T and B cells. Defects encompassing a broad range of these attributes have been reported in cells from neonates. As a result responses following infection and vaccination are qualitatively and quantitatively reduced in these individuals compared to adults.