title: 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.
authors.affiliation: Mucosal Infection and Immunity Group, Section of Infectious Diseases, Department of Medicine, Imperial College London, London W2 1PG, United Kingdom. john.tregoning@imperial.ac.uk
authors.forename: John S
authors.initials: JS
authors.lastname: Tregoning
authors.forename: Belinda Lei
authors.initials: BL
authors.lastname: Wang
authors.forename: Jacqueline U
authors.initials: JU
authors.lastname: McDonald
authors.forename: Yuko
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: James A
authors.initials: JA
authors.lastname: Harker
authors.forename: Michelle
authors.initials: M
authors.lastname: Goritzka
authors.forename: Cecilia
authors.initials: C
authors.lastname: Johansson
authors.forename: Alexander
authors.initials: A
authors.lastname: Bukreyev
authors.forename: Peter L
authors.initials: PL
authors.lastname: Collins
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Openshaw
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000914:Antibodies, Viral / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D007371:Interferon-gamma