Neonatal antibody responses are attenuated by interferon-γ produced by NK and T cells during RSV infection

Abstract

Respiratory syncytial virus (RSV) infects most children in the first year of life and is a major single cause of hospitalization in infants and young children. There is no effective vaccine, and antibody generated by primary neonatal infection is poorly protective against reinfection even with antigenically homologous viral strains. Studying the immunological basis of these observations in neonatal mice, we found that antibody responses to infection were low and unaffected by CD4 depletion, in contrast with adult mice, which had stronger CD4-dependent antibody responses. Natural killer cell depletion or codepletion of CD4 + and CD8 + cells during neonatal RSV infection caused a striking increase in anti-RSV antibody titer. These cells are major sources of the cytokine IFN-γ, and blocking IFN-γ also enhanced RSV-specific antibody responses in neonates. In addition, infection with a recombinant RSV engineered to produce IFN-γ reduced antibody titer, confirming that IFN-γ plays a pivotal role in inhibition of antibody responses after neonatal infection. These unexpected findings show that the induction of a strong cellular immune response may limit antibody responses in early life and that vaccines that induce IFN-γ-secreting cells might, in some situations, be less protective than those that do not.viral infection | bronchiolitis | lung infection

Contribution of Fcγ receptors to human respiratory syncytial virus pathogenesis and the impairment of T‐cell activation by dendritic cells

“…The findings described here, which show that hRSV remains infective in DCs and alters their capacity to activate naive T cells despite being bound to neutralizing antibodies is consistent with the notion that naturally occurring anti‐hRSV antibodies can fail at establishing an effective immunity to the virus, although there are conflicting results . Along these lines, the contribution of maternal antibodies to protection against hRSV remains controversial.…”

Vaccines against Respiratory Viral Pathogens for Use in Neonates: Opportunities and Challenges

“…While increased relative to IgG, IgM responses are also impaired as exemplified by RSV infection of human infants where both IgM and IgG responses are poor (23). Similar findings have been reported in murine models (24). Isotype analysis showed a skewing towards IgG1, indicating a Th2 biased response (24).…”

“…Similar findings have been reported in murine models (24). Isotype analysis showed a skewing towards IgG1, indicating a Th2 biased response (24). Important contributors to the poor antibody response in infants are impaired accessory cells, i.e.…”

A genetic model of differential susceptibility to human respiratory syncytial virus (RSV) infection

“…A role for interferon α (IFN‐α), IFN‐β, and IFN‐γ in the innate immune response to RSV has been demonstrated by previous studies (27–29). Among Northern Europeans, small but statistically significant increases in mean IFN‐α ( IFNA ) mRNA were found and differed between lines ( e.g.…”