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1976 Swine Flu Vaccination and 2009 H1N1

By Amesh A. Adalja, MD, April 30, 2010

It is well established that the 2009 H1N1 virus affected younger people disproportionally and that older people are more likely to have immunity to the virus. There are several possible reasons for this. According to a newly published study, one reason appears to be the 1976 swine flu vaccination campaign.

2009 H1N1 Similar to 1976 Swine Flu Virus

2009 H1N1 is genetically more similar to seasonal H1N1 strains from the 1930s and 1940s than it is to seasonal influenza viruses that were circulating immediately prior to the pandemic. But phylogenetic analysis indicates that the virus most closely related to the 2009 H1N1 strain is the A/New Jersey/1976, which is the virus responsible for the outbreak of “swine flu” in the spring of 1976  at Fort Dix , New Jersey. That outbreak led to the first ever effort to vaccinate the entire U.S. population against influenza. In that campaign, 45 million people (approximately 25% of the U.S. population) were vaccinated. A new study, published by a group of investigators from St. Jude Children’s Research Hospital, assessed the degree to which vaccination in 1976 conferred protection against the 2009 H1N1 strain.

Highly Vaccinated Study Group

McCullers and colleagues recruited 110 St. Jude’s employees for the study group. All subjects were over the age of 55, and 94 % had received the seasonal influenza vaccine the year prior to the study. None had been vaccinated against 2009 H1N1 influenza. Forty six subjects (42%) had been vaccinated in 1976 with the A/New Jersey/1976 vaccine. Discarded pediatric serum samples from 2001 were used as a control.

Seasonal Immune Responses High

As expected, nearly 90% of subjects were found to have immunity to the 2008-09 seasonal influenza A H1N1 strain with antibody titers > 40 by hemagglutinin inhibition assay. Interestingly, nearly the same percentage (89%) had comparable titers  to the 2009 H1N1 strain, presumably due to prior infection with or vaccination against a closely related strain. Almost none of pediatric controls had protective titers. While nearly all subjects had some immunity to both the seasonal and pandemic viruses, the quality of that immunity was not the same. There was a difference in the titers of neutralizing antibodies to the seasonal and pandemic viruses. Only 18% of the subjects had elevated levels of neutralizing antibodies to the pandemic virus, whereas 68% had neutralizing antibodies to the seasonal strain.

1976 Vaccine Recipients Exhibit Stronger Protection

Of the 44 subjects who received the 1976 vaccine, HAI antibody titers were similar to those who had not received the vaccine (nearly all had elevated titers in both groups). However, neutralizing antibody titers were significantly higher in those who had received the 1976 vaccine. Titers >160 were achieved in 8 of the 46 recipients (17%) of the 1976 vaccine, while only 3 of 70 (4%) nonrecipients reached this level—a statistically significant number.

Vaccine Does Not Explain All

Although the 1976 vaccine conferred some level of protection, it is not enough to account for the age distribution of 2009 H1N1 cases. As the authors of the study acknowledge, many other nations did not undertake a vaccination program similar to the 1976 U.S. effort and have the same age distribution of 2009 H1N1 cases as that of the U.S. In fact, only 25% of the U.S. population was vaccinated in 1976, leaving most people without the modest degree of protection conferred by the vaccine. This finding points to other factors that may be responsible for the protection of the elderly observed in 2009, including enhanced immunity resulting from infection with a similar H1N1 strain circulating prior to 1957.

Reference

McCullers JA, Van De Velde L, Allison KJ, et al. Recipients of vaccine against the 1976 "swine flu" have enhanced neutralization responses to the 2009 novel H1N1 virus. Clin Infect Dis 2010:50. http://www.journals.uchicago.edu/doi/abs/10.1086/652441. Accessed April 26, 2010.