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Flu exposure may reduce vaccine effectiveness for some

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February 3, 2018

Brendan Flannery

An age cohort’s first influenza A(H1N1) exposure may have greatly dulled the effectiveness of a recent vaccine, according to researchers.

Patients born between 1958 and 1979 may have been more vulnerable to infection because their first A(H1N1) exposure primed them for an immune response that did not fit changes in a recent strain, the researchers wrote in The Journal of Infectious Diseases. Their data were gathered during several recent influenza seasons in which circulating viruses were related to that of the 2009 pandemic. They show that changes to influenza viruses may necessitate updates to vaccines.

“Reduced [vaccine effectiveness (VE)] associated with changes in circulating viruses may signal the need for updating vaccine components even when antigenic changes are not detected with ferret antisera,” researcher Brendan Flannery, PhD, an epidemiologist at the CDC’s Influenza Division, and colleagues wrote. “These results reinforce the need for human serologic data and VE studies, in addition to traditional ferret studies, to monitor changes in influenza viruses and inform vaccine strain selection.”

To determine the potential impact of an individual’s first A(H1N1) exposure on vaccine effectiveness, the researchers formed age cohorts based on the influenza viruses for which people were most likely to be primed according to their birth years. They then calculated VE for five influenza seasons, starting with that of 2011-2012. They excluded the 2014-2015 season because circulation of A(H1N1)pdm09 viruses was more limited then. The researchers based their calculations on data from the U.S. Flu VE Network, a group of university and hospital researchers who estimate influenza VE across the country.

During the seasons included in the study, 2,115 patients tested positive for A(H1N1)pdm09. Another 14,696 patients tested negative for influenza during weeks with laboratory-confirmed A(H1N1)pdm09 viruses.

In all, 7,002 patients without influenza (48%) and 597 patients with A(H1N1)pdm09 (28%) had been vaccinated at least 14 days before illness onset, the researchers said.

Among the 1958-1979 birth cohort, VE for the first three seasons in the study was 61%. Among the same cohort, VE dipped to 56% during 2013-2014, then dropped sharply to 22% in 2015-2016. The low VE that season in the 1958-1979 cohort lowered the overall VE among all age cohorts to 47%, the researchers said. Otherwise, excluding the 1958-1979 group showed the VE among all others to be 61% that season.

According to the researchers, the vast disparity might be explained by a change in A(H1N1)pdm09 viruses for which the cohort was not primed. A(H1N1) viruses stopped circulating in 1957, then resumed in 1977. Therefore, for people born between 1958 and 1979, their first A(H1N1) exposure was presumed to be that of the virus A/USSR/90/1977.


Previous studies have suggested that initial exposure to an influenza virus can long influence a patient’s immune response, a notion known as “original antigenic sin.” That can mean that the patient’s immune response is primed over the long term to respond more robustly to influenza with the same epitopes as those of the initial virus. But it is not primed to respond as robustly against a virus with different epitopes or other changes, perhaps a virus for which the patient was more recently vaccinated.

Flannery and colleagues explained that in 2013-2014 and then in 2015-2016, new genetic groups among A(H1N1)pdm09 viruses became predominant. They were the 6B and 6B1 groups, respectively. A change in the 6B1 group may have inhibited antibodies in the 1958-1979 cohort from attaching to epitopes — an immune response that would more likely have occurred in viruses without such changes.

In efforts to improve VE, the A(H1N1) vaccine component was changed for the 2017 Southern Hemisphere season and the 2017-2018 Northern Hemisphere season.

In a related commentary, Allen C. Cheng, PhD, MPH, of the Monash University School of Public Health and Preventive Medicine, and Kanta Subbarao, MBBS, MPH, director of the WHO Collaborating Centre for Reference and Research on Influenza — both in Australia —agreed that changes seen in the 6B1 viruses likely inhibited immune response. However, they also noted difficulties in matching vaccines to influenza strains. Specifically, Cheng and Subbarao pointed to influenza A(H3N2) viruses and their ability to elude vaccines. H3N2 has dominated the 2017-2018 influenza season in the United States. In any case, they maintained, Flannery and colleagues have shown that more work is needed in targeting influenza viruses.

“It took [more than] 50 years after the implementation of influenza vaccines to develop systems to routinely monitor their effectiveness,” they wrote. “The subsequent 10 to 15 years of data suggest that, while the vaccines are generally protective, the degree of protection varies from season to season and that, importantly, as highlighted in the current article, it may be lower in certain population groups. These population-level data demonstrate that current vaccines are moderately protective at best, and more effective vaccines are clearly needed.” – by Joe Green

Disclosures: Cheng, Flannery and Subbarao report no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.