Annual Vaccination against Influenza Virus May Hamper Development of Immunity in Children

[Gert van der Hoek]

Annual childhood flu vaccines may interfere with development of crossresistance

Friday, November 25th, 2011 | health blog


Vaccinating children annually against influenza virus interferes with their development of cross-reactive killer T cells to flu viruses generally, according to a paper in the November Journal of Virology.


In this study, first author Rogier Bodewes of Erasmus Medical Center, Rotterdam, The Netherlands and his collaborators collected blood samples from Dutch children with cystic fibrosis, who are vaccinated annually against influenza, and from healthy control children who are not vaccinated, and tested both sets of blood samples for the presence of virus-specific killer T cells. The majority of virus-specific killer T cells are directed to conserved viral proteins, that is, proteins that are very similar among different flu viruses, unlike the rapidly evolving, highly variable proteins which are targets of antibodies induced by influenza vaccines.


In unvaccinated children, the investigators found that the number of virus-specific T cells rises with age, while such an increase was absent in children vaccinated annually. In fact, vaccination appeared to interfere with induction of such killer T cells, says Bodewes.

“Vaccinated children with [cystic fibrosis] will develop lower cross-reactive virus-specific CD8+ T cell responses than unvaccinated children,” says the study.

“Most countries recommend annual flu vaccination of certain high risk groups to protect against seasonal influenza,” says Bodewes. “Furthermore, some countries recommend annual influenza vaccination of all healthy children more than six months of age.”


The research points up potentially conflicting policy outcomes. Annual flu vaccines are effective against seasonal flu, but could leave people more vulnerable to novel pandemics, says Bodewes, as induction of virus-specific killer T cells caused by childhood flu infection may reduce morbidity and mortality rates from pandemic influenza viruses. Referring to the paper, he says that the findings “highlight the need for the development and use of universal influenza A virus vaccines for children, especially in light of the pandemic threat of avian influenza A/H5N1.” Nonetheless, he says that efforts to develop such vaccines have for several decades been stymied by the sheer complexity of targeting inner proteins.

Journal Reference:

R. Bodewes, P. L. A. Fraaij, M. M. Geelhoed-Mieras, C. A. van Baalen, H. A. W. M. Tiddens, A. M. C. van Rossum, F. R. van der Klis, R. A. M. Fouchier, A. D. M. E. Osterhaus, G. F. Rimmelzwaan. Annual Vaccination against Influenza Virus Hampers Development of Virus-Specific CD8+ T Cell Immunity in Children. Journal of Virology, 2011; 85 (22): 11995 DOI: 10.1128/JVI.05213-11


Medicalzone

[tetano]

First published August 2011, doi: 10.1128/​JVI.05213-11 J. Virol. November 2011 vol. 85 no. 22 11995-12000


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

Rogier Bodewes1,
Pieter L. A. Fraaij1,2,
Martina M. Geelhoed-Mieras1,
Carel A. van Baalen3,
Harm A. W. M. Tiddens4,
Annemarie M. C. van Rossum5,
Fiona R. van der Klis6,
Ron A. M. Fouchier1,
Albert D. M. E. Osterhaus1,3 and
Guus F. Rimmelzwaan1,3,*

1Department of Virology, Erasmus Medical Center, Rotterdam, The Netherlands
2Intensive Care and Department of Pediatric Surgery, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands
3ViroClinics Biosciences B.V., Rotterdam, The Netherlands
4Department of Pediatrics, Respiratory Medicine and Allergology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands
5Department of Pediatrics, Division of Infectious Diseases and Immunology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands
6National Institute for Public Health and the Environment, Laboratory for Infectious Diseases and Screening, P.O. Box 1, 3720 BA Bilthoven, The Netherlands

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. The consequences of these findings are discussed in the light of the development of protective immunity to seasonal and future pandemic influenza viruses.

http://jvi.asm.org/content/85/22/119...3-e71cb8a8a7ea