Potential antigenic explanation for atypical H1N1 infections among middle-aged adults during the 2013–2014 influenza season

• Published in: Proceedings of the National Academy of Sciences - PNAS 2014-11, Vol.111 (44), p.15798-15803
• Main Authors: Linderman, Susanne L., Chambers, Benjamin S., Zost, Seth J., Parkhouse, Kaela, Li, Yang, Herrmann, Christin, Ellebedy, Ali H., Carter, Donald M., Andrews, Sarah F., Zheng, Nai-Ying, Huang, Min, Huang, Yunping, Strauss, Donna, Shaz, Beth H., Hodinka, Richard L., Reyes-Terán, Gustavo, Ross, Ted M., Wilson, Patrick C., Ahmed, Rafi, Bloom, Jesse D., Hensley, Scott E.
• Format: Article
• Language: English
• Subjects: Adult; Adults; Animals; Antibodies; Antigens, Viral - genetics; Antigens, Viral - immunology; Avian flu; Biological Sciences; Epitopes; Female; Glycoproteins; H1N1 subtype influenza A virus; Hemagglutinin Glycoproteins, Influenza Virus; Humans; Infections; Influenza A Virus, H1N1 Subtype - genetics; Influenza A Virus, H1N1 Subtype - immunology; Influenza A Virus, H1N1 Subtype - pathogenicity; Influenza Vaccines; Influenza, Human - genetics; Influenza, Human - immunology; Influenza, Human - mortality; Male; Mice; Mice, Inbred BALB C; Middle age; Middle Aged; Mutation; Older adults; Orthomyxoviridae; Pandemics; Vaccination; Viral infections; Viruses
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1409171111

Influenza viruses typically cause the most severe disease in children and elderly individuals. However, H1N1 viruses disproportionately affected middle-aged adults during the 2013–2014 influenza season. Although H1N1 viruses recently acquired several mutations in the hemagglutinin (HA) glycoprotein, classic serological tests used by surveillance laboratories indicate that these mutations do not change antigenic properties of the virus. Here, we show that one of these mutations is located in a region of HA targeted by antibodies elicited in many middle-aged adults. We find that over 42% of individuals born between 1965 and 1979 possess antibodies that recognize this region of HA. Our findings offer a possible antigenic explanation of why middle-aged adults were highly susceptible to H1N1 viruses during the 2013–2014 influenza season. Our data further suggest that a drifted H1N1 strain should be included in future influenza vaccines to potentially reduce morbidity and mortality in this age group. Significance Influenza viruses typically cause a higher disease burden in children and the elderly, who have weaker immune systems. During the 2013–2014 influenza season, H1N1 viruses caused an unusually high level of disease in middle-aged adults. Here, we show that recent H1N1 strains possess a mutation that allows viruses to avoid immune responses elicited in middle-aged adults. We show that current vaccine strains elicit immune responses that are predicted to be less effective in some middle-aged adults. We suggest that new viral strains should be incorporated into seasonal influenza vaccines so that proper immunity is elicited in all humans, regardless of age and pre-exposure histories.