Determinants of early life immune responses to RSV infection

Abstract

Respiratory syncytial virus causes significant morbidity and mortality in both developed and developing countries, and a vaccine that adequately protects from severe disease remains an important unmet need. RSV disease has an inordinate impact on the very young, and the physical and immunological immaturity of early life complicates vaccine design. Defining and targeting the functional capacities of early life immune responses and controlling responses during primary antigen exposure with selected vaccine delivery approaches will be important for protecting infants by active immunization. Alternatively, vaccination of older children and pregnant mothers may ameliorate disease burden indirectly until infants reach about six months of age, when they can generate more effective anti-RSV immune responses.

Published by Elsevier B.V.

Figures

Figure 1. Optimal antigen design coupled with selected age-specific adjuvants can alter DC function during infant vaccination and promote effective anti-viral memory responses

The use of adjuvants with known responsiveness in neonates couldenhance the function of early-lifeplasmacytoid dendritic cells (PDC), follicular dendritic cells (FDC), and lung-migratory CD103+ and CD11b+ DC populations to support the development of anti-viral B and T cell responses. Effectively targeting and using DCs to promote Th1 and TFH may assist with the generation of cytotoxic T lymphocytes (CTL) and high-affinity, neutralizing antibody production by B cells, respectively. Promoting the maturation of CD103+ DCs in the lung could enhance costimulatory signals and cytokine production, and lead to the induction of anti-viral CTL.