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

John S. Tregoning, Belinda Lei Wang, Jacqueline U. McDonald, Yuko Yamaguchi, James A. Harker, Michelle Goritzka, Cecilia Johansson, Alexander Bukreyev, Peter L. Collins, Peter J. Openshaw

Research output: Contribution to journalArticle

23 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)5576-5581
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number14
DOIs
StatePublished - Apr 2 2013

Keywords

  • Bronchiolitis
  • Lung infection
  • Viral infection

ASJC Scopus subject areas

  • General

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    Tregoning, J. S., Wang, B. L., McDonald, J. U., Yamaguchi, Y., Harker, J. A., Goritzka, M., Johansson, C., Bukreyev, A., Collins, P. L., & Openshaw, P. J. (2013). Neonatal antibody responses are attenuated by interferon-γ produced by NK and T cells during RSV infection. Proceedings of the National Academy of Sciences of the United States of America, 110(14), 5576-5581. https://doi.org/10.1073/pnas.1214247110