Responses to the Sb epitope contributed to antigenic drift of the influenza A 2009 H1N1 virus
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ORIGINAL ARTICLE
Responses to the Sb epitope contributed to antigenic drift of the influenza A 2009 H1N1 virus S. Ketklao1 · C. Boonarkart1 · S. Phakaratsakul1 · P. Auewarakul1 · Ornpreya Suptawiwat2 Received: 21 March 2020 / Accepted: 27 June 2020 © Springer-Verlag GmbH Austria, part of Springer Nature 2020
Abstract Immunodominance is recognized as a key factor in the antigenic drift of seasonal influenza viruses. In the immunodominance model, each individual in a population predominantly responds to a single epitope among the five antigenic epitopes of the viral hemagglutinin (HA), driving escape mutations one at a time, and sequential mutations in multiple individuals who respond to different epitopes eventually generate a drifted strain with mutations in epitopes that are targeted by a majority of the population. A focused antibody response to the Sa epitope in people born between 1965 and 1979 was believed to contribute to a mutation at HA residue 163 and the first antigenic drift of the 2009 pandemic influenza A H1N1 virus. A serine-to-threonine mutation at HA residue 185 in the Sb epitope emerged in 2010 even before the 163 mutation. We show here that a large fraction of the population in 2010-2011 had responses to the Sb epitope, as shown by 47% of tested sera having altered titers to the S185T mutant. Responses to the Sb epitope showed an age-specific trend similar to that found for the response to Sa epitope in these subjects. Together, the focused responses to Sa and Sb epitopes may have driven the first antigenic drift of the 2009 pandemic H1N1 virus.
Introduction Antigenic drift plays a pivotal role in the evolution and persistence of seasonal influenza in the human population. It is a global-scale event that allows new strains to infect people who have been infected and are immune to previously circulating strains. A drifted strain usually carries mutations in several major epitopes of the viral HA surface protein. There are five major B cell epitopes located around the receptorbinding site on the HA head of influenza A H1N1 – Sa, Sb, Ca1, Ca2, and Cb – which are the main targets of hemagglutination-inhibiting and neutralizing antibodies [1–3].
Handling Editor: Ayato Takada. S. Ketklao and C. Boonarkart contributed equally to this manuscript. * Ornpreya Suptawiwat [email protected] 1
Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
Faculty of Medicine and Public Health, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand
2
While the mutation rate of influenza virus is high, it is not high enough to allow mutations in all five major epitopes to arise simultaneously in an infected individual or even in the whole world population. Therefore, it is believed that antigenic drift occurs in a stepwise fashion. An individual predominantly responds to one or a few epitopes and drives mutations only in that particular epitope. Mutations accumulate after the virus sequentially infects multiple individuals who respond to
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