Cross-Reactive Antibody Responses to the 2009 Pandemic H1N1 Influenza Virus
Hancock K, Veguilla V, Lu X, et al
N Engl J Med. 2009;361 Sep 10 [Epub ahead of print]
Study Summary
The over-arching goal of this study was to determine whether existing antibodies to either seasonal influenza virus or to the 1976 swine H1N1 virus demonstrated cross-reactivity to the current 2009 H1N1 pandemic influenza strain. The participants and sera were drawn from multiple sources; the intent was to provide a broad picture of the general cross-reactivity to pandemic 2009 H1N1 among children, adults, and older adults. The investigators used stored serum samples from vaccine trials in 1976, and from 2005 through 2009, as well as samples collected for other purposes in 1971 and from 2002 through 2009. Investigators tested the samples for reactivity to 2009 H1N1, 2009 seasonal influenza A H1N1, and 1976 swine influenza A. Samples were considered cross-reactive if the titers met prespecified goals that correlated with an approximately 50% reduction in risk for infection with influenza.
Investigators detected no cross-reactive antibody response among 124 people aged 6 months - 9 years, except in 1 child who had a titer above the cutoff value. Likewise, the subset of children who received either injectable or nasal seasonal influenza vaccine did not mount a cross-reactive response to 2009 H1N1. After receiving seasonal influenza vaccines, 7% of people aged 18-40 years and 25% of people aged 18-64 years also exhibited cross-reactive antibodies to 2009 H1N1. To illustrate the birth-cohort effect of reactivity against 2009 H1N1, the investigators also tested samples from 417 individuals born between 1880 and 2004. They found that all 11 donors born from 1910 to 1929 achieved effective titers against 2009 H1N1. The prevalence was 34% among donors born before 1950 and only 4% among donors born after 1980. Of the 83 adults who received the 1976 H1N1 vaccine, 54% had antibodies cross-reactive to 2009 H1N1.
The investigators concluded that seasonal influenza vaccines, regardless of the year or decade administered, appear to offer little protection against 2009 H1N1 influenza. Although children had no preexisting immunity to 2009 H1N1, many adults appear to have preexisting immunity to this virus. In older adults, exposure to a 1918 H1N1-like virus likely accounts for the cross-reactivity seen against 2009 H1N1.
Viewpoint
This study offers a fascinating glimpse into the natural history of H1N1 viruses, including the swine variants, across the past century. The study authors speculate that cross-reactivity to 2009 H1N1 conferred by previous exposure to older H1N1 variants accounts for the observation that to date, the 2009 H1N1 virus has produced more disease in children and young adults than in older adults, a group classically considered vulnerable to seasonal influenza viruses. For pediatricians, these data drive home the point that children need both the seasonal and 2009 H1N1 vaccines this year. The Centers for Disease Control and Prevention's (CDC's) 2009 H1N1 Flu Website is an excellent resource for practitioners who wish to stay up to date on H1N1 issues.
Abstract