Do Yearly Influenza Vaccinations for Children Affect Immunity Against Pandemic Strains?

Laurie Barclay, MD

October 29, 2009

October 29, 2009 — Whether yearly vaccinations for children against seasonal influenza might stop immunity developing against pandemic strains is debated in a personal view and reflection and reaction published online October 30 and will appear in the December print edition of The Lancet Infectious Diseases.

"Yearly vaccination is necessary because of the substantial antigenic drift of influenza viruses that necessitates the update of vaccines every year...driven by selective pressure mediated by antibodies induced by natural infection or vaccination," write Rogier Bodewes, DVM; Joost H.C.M. Kreijtz, PhD; and Guus F. Rimmelzwaan, PhD, from Erasmus Medical Center in Rotterdam, The Netherlands.

"The vaccination of healthy children aged 6–59 months against seasonal influenza has been recommended in several countries, including the USA and some European countries," the authors continue, "because the disease is an important cause of illness and admission to hospital in this age group. Although annual vaccination against seasonal influenza is beneficial for all patients at high risk, including children, vaccination of the 6–59 month age group every year against seasonal influenza might have a downside that has not been given much thought."

Previous studies, mostly in mice and other animals, have shown that infection with influenza A viruses can induce heterosubtypic immunity, which is protective immunity to influenza A viruses of other unrelated subtypes. Although heterosubtypic immunity does not offer full protection, it can limit virus replication and reduce influenza symptoms and mortality in the host.

The authors note that the ramifications of heterosubtypic immunity should be considered in humans when a new subtype of influenza A virus is introduced into the population. Pertinent examples include the novel influenza A H1N1 virus causing the present influenza pandemic and the highly pathogenic avian influenza H5N1 viruses responsible for increasing numbers of human infections, which are often fatal.

The authors suggest that an untoward effect of preventing infection with seasonal influenza viruses by vaccination might be to prevent the induction of heterosubtypic immunity to pandemic strains. Infants and other immunologically naive individuals would be at greatest risk were this to occur.

To test their theory, the authors suggest that hospitalizations and mortality rates among infants who have received yearly influenza vaccination since birth should be closely monitored and compared with those in age-matched children who were not vaccinated. The present H1N1 pandemic offers a unique opportunity to investigate heterosubtypic immunity and to determine potential harms of annual influenza vaccination.

In the meantime, the authors support the current vaccination program against H1N1 influenza and acknowledge that it will decrease morbidity and deaths in all age groups.

"Use of these pandemic influenza vaccines will override the theoretical issues associated with yearly vaccination against seasonal influenza," the study authors conclude. "The development and use of vaccines that can induce broad protective immunity might be a solution for these potential problems and we think this is a priority."

In an accompanying reflection and reaction, Terho Heikkinen, MD, and Ville Peltola, MD, from Turku University Hospital in Finland, argue that prevention of seasonal influenza in children by vaccination far outweighs the theoretical risk of preventing the induction of heterosubtypic immunity to pandemic strains. However, they agree with Dr. Bodewes and colleagues that more effective influenza vaccines that could induce broader immune responses are needed.

"The results of experimental animal studies can never be extrapolated directly to human beings, let alone form the basis of any vaccination policy," Dr. Heikkinen and Dr. Peltola write. "There is ample evidence for the great burden of influenza in young children, and this burden appears during every influenza season. By contrast, there is no clinical evidence that vaccinating children against influenza would prevent the induction of heterosubtypic immunity and thereby be disadvantageous to children in the long run."

Dr. Heikkinen and Dr. Peltola therefore advocate continuing the ongoing influenza vaccination program.

"While waiting for improved influenza vaccines, the simple question is should we let young children suffer from a severe and potentially lethal but easily preventable illness, just because there is a theoretical possibility that withholding vaccination might result in a slightly less severe illness sometime in the future?" they conclude. "We believe that the answer to this question is a simple one."

Dr. Rimmelzwaan is a consultant to Viroclinics BV. The other 2 personal view authors have disclosed no relevant financial relationships. Dr. Heikkinen has provided consultancy services to Novartis, Medimmune, GlaxoSmithKline, and Solvay. Dr. Peltola has received grants from GlaxoSmithKline and provided consultancy services to Novartis.

Lancet Infect Dis. Published online October 30, 2009.

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