Annual Vaccination against Influenza Virus Hampers Development of Virus-Specific CD8⁺T Cell Immunity in Children

Abstract

Infection with seasonal influenza A viruses induces immunity to potentially pandemic influenza A viruses of other subtypes (heterosubtypic immunity).We recently demonstrated that vaccination against seasonal influenza prevented the induction of heterosubtypic immunity against influenza A/H5N1 virus induced by infection with seasonal influenza in animal models, which correlated with the absence of virus-specific CD8 ؉ T cell responses. Annual vaccination of all healthy children against influenza has been recommended, but the impact of vaccination on the development of the virus-specific CD8؉ T cell immunity in children is currently unknown. Here we compared the virus-specific CD8؉ T cell immunity in children vaccinated annually with that in unvaccinated children. In the present study, we compared influenza A virus-specific cellular and humoral responses of unvaccinated healthy control children with those of children with cystic fibrosis (CF) who were vaccinated annually. Similar virus-specific CD4؉ T cell and antibody responses were observed, while an age-dependent increase of the virus-specific CD8 ؉ T cell response that was absent in vaccinated CF children was observed in unvaccinated healthy control children. Our results indicate that annual influenza vaccination is effective against seasonal influenza but hampers the development of virus-specific CD8 ؉ T cell responses.

Repeated annual influenza vaccination and vaccine effectiveness: review of evidence

“…There is evidence from animal studies that repeated vaccination can interfere with the development of cross-reactive immunity against other subtypes, likely mediated by reduced virusspecific CD8+ T cell response [51,52]. In children, annual vaccination has also been demonstrated to hamper development of virus-specific CD8+ T cell immunity [53]. The implications remain unclear, but these findings raise the possibility that repeated vaccination of low-risk individuals could affect the occurrence or severity of illness caused by a new pandemic virus or a new seasonal virus antigenic cluster.…”

A Systematic Review of the Efficacy of Live Attenuated Influenza Vaccine Upon Revaccination of Children

“…These children received influenza vaccine annually, compared with previously unvaccinated healthy children. 8 Annual influenza vaccination with IIV was shown to hamper the development of virus- specific CD8C T cell responses. However, a review article by Belshe et al 9 showed that LAIV efficacy did not decrease with increasing pre-existing immunity to influenza in children 15 to 84 months of age compared with placebo or in children 6 months to 17 years of age compared with trivalent IIV.…”

2012/13 influenza vaccine effectiveness against hospitalised influenza A(H1N1)pdm09, A(H3N2) and B: estimates from a European network of hospitals

“…Concerns have been raised from animal data that early and repeated vaccination with nonadjuvanted inactivated vaccines may interfere with heterosubtypic immunity and therefore increase susceptibility to illness with heterotypic strains. [187,188] This might be of particular concern in the setting of the emergence of pandemic influenza viruses. However, the theoretical dangers of early and repeated vaccination of children are outweighed by the disease reduction associated with protection against currently circulating subtypes.…”