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Yearly influenza vaccines may affect natural immunities

Bodewes R. J. Virol. 2011;85:11995-12000.

A group of children who had cystic fibrosis and received annual influenza vaccines developed lower cross-reactive virus-specific CD8+ T-cell responses than unvaccinated children, according to a study by Rogier Bodewes, DVM, and colleagues from the Erasmus Medical Center in Rotterdam.

The researchers collected blood samples from 14 Dutch children with cystic fibrosis who were vaccinated and from 27 healthy control children who were not vaccinated, and they tested both sets of blood samples for the presence of virus-specific killer T cells.

In unvaccinated children, the number of virus-specific T cells rises with age, whereas such an increase was absent in children vaccinated annually, the researchers said, adding that vaccination appeared to interfere with induction of such killer T cells.

“In unvaccinated children, an age-dependent increase in the frequency of virus-specific CD8 T cells, which was not observed in vaccinated children with [cystic fibrosis], was detected,” the researchers wrote. “It has been demonstrated previously that the majority of influenza A virus-specific CD8 T cells is directed to conserved viral proteins. This indicates that memory CD8 T cells provoked against seasonal influenza A viruses will cross-react with other influenza A viruses, even with those of other subtypes. Thus, vaccinated children with [cystic fibrosis] will develop lower cross-reactive virus-specific CD8 T-cell responses than unvaccinated children.”

The data suggest that although influenza vaccines are effective against seasonal influenza, vaccines could leave patients more vulnerable to novel pandemics, as induction of virus-specific killer T cells caused by childhood influenza infection may reduce morbidity and mortality rates from pandemic influenza viruses.

Referring to the paper in a press release, Bodewes said 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, Bodewes said efforts to develop such vaccines have for several decades been stymied by the sheer complexity of targeting inner proteins.

In the 1970s, Hoskins and colleagues published three papers in The Lancet that suggested immunity against subsequent influenza infections afforded by natural influenza infection was more effective than vaccine-induced protection, and that repeated yearly vaccinations did not confer long-term protection. They evaluated adolescent boarding school attendees during four influenza seasons and concluded that annual repeated influenza vaccinations did not confer protection and termed this the “Hoskins” effect. However, subsequent review of these papers questioned the conclusions because most of the study subjects were not vaccinated every year and no negative effect of repeated vaccination could be detected.

Many continue to question the effectiveness of the influenza vaccines and the impact of yearly vaccination. The recent paper by Bodewes and colleagues from the Erasmus Medical Center in Rotterdam suggests that the annual vaccination against influenza virus hampers the development of virus-specific CD8 T cells in children. However, the implications of these laboratory findings for the impact on disease burden are not clear. What is clear is that influenza vaccines are not perfect, and that at the extremes of age in the very young and the very old, they need to be improved. The use of highly active adjuvants, the use of higher doses of vaccine, and the use of live-attenuated vaccines in children are ways to circumvent some of these inadequacies of inactivated influenza vaccines.

Research must continue on how to improve our influenza vaccines, but in the meantime, the current vaccines should be used to protect our children.

–Kathryn M. Edwards, MD

Infectious Diseases in Children Editorial Board

Disclosure: Dr. Edwards reports no relevant financial disclosures.

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