NEW YORK (Reuters Health) – In 2009, people given the seasonal trivalent influenza vaccine were at higher risk of infection with the pandemic H1N1 strain than those given a placebo injection, according to a study from Hong Kong. It seems that those not vaccinated were more likely to acquire seasonal flu infection, and this protected against pandemic H1N1 infection.

Writing in Clinical Infectious Diseases for December 15, Dr. Benjamin J. Cowling, and colleagues at the University of Hong Kong say there has been “intense interest” in the effect of seasonal flu vaccination on the risk of pandemic H1N1 infection, because one study from Canada suggested the flu vaccine increased the risk of H1N1 infection while others have reported opposite or inconclusive findings.

To investigate this question, the researchers took advantage of a placebo-controlled influenza vaccine trial in children, which was already in place in 2009 when the novel H1N1 strain became widespread.

As expected, the trivalent influenza vaccine (TIV) was protective against season flu. “By the end of the study period, 8% and 7% of the children in the TIV group had serologically confirmed infection with seasonal influenza A/H1N1 and A/H3N2, compared with 21% and 12%, respectively, in the control group,” according to the report.

However, after adjustment, the team estimated that 31% of children who received TIV were infected with pandemic A/H1N1, compared with 12% of children who received placebo (p=0.04).

Further analysis showed that the rate of confirmed pandemic H1N1 infection was 8% among those with confirmed seasonal influenza infection during the follow-up period, compared with 20% who did not have confirmed seasonal flu.

“In multivariable analysis, those infected with seasonal influenza A during the study had a lower risk of laboratory-confirmed pandemic A/H1N1 infection (adjusted odds ratio [OR], 0.35), and receipt of seasonal TIV was unassociated with risk of pandemic A/H1N1 infection (adjusted OR, 1.11),” according to the report.

The author of a related editor, Dr. W. Paul Glezen commented via email, “The study from Hong Kong allays concern created by the report from Canada that implied a deleterious effect of seasonal influenza vaccine on risk of infection with the pandemic influenza A(H1N1) virus.”

Dr. Cowling and colleagues suggest the cross-protective effect of seasonal flu infection against H1N1 may be attributable to mechanisms such as cell-mediated immunity rather than a cross-reactive antibody response, and they note that inactivated vaccines do not induce an efficient CD8+ T cell response.

“Alternative vaccines, such as live attenuated vaccines or adjuvanted vaccines, may confer greater cross-protection against heterologous strains and avoid this potential disadvantage of TIV,” the authors suggest in their conclusion.

Dr. Glezen, of Baylor College of Medicine, Houston, Texas, agrees. In his editorial, he points out that the live attenuated influenza vaccine (LAIV) “mimics natural infection by stimulating immunity by multiple mechanisms.” LAIV provides almost immediate protection against respiratory viruses, giving time for specific immunity to develop.

He concludes, “LAIV should be the vaccine of choice for healthy children and adults, especially when influenza is prevalent in the community.” He added via email, “Studies have shown that the live attenuated vaccine administered by nasal spray is more efficacious for eligible children in the pediatric age group.”

Asked if pandemic H1N1 is as much of an issue, now that the antigen is included in the current trivalent vaccine, he responded, “The immediate threat for this season appears to the new variant of influenza A(H3N2), A/Perth. Fortunately, this variant is in the current trivalent influenza vaccine and advantage of this should be realized by taking the vaccine as soon as possible.”

Clin Infect Dis 2010;51.