Antigenicity of the 2015-2016 Seasonal H1N1 Human Influenza Virus HA and NA Proteins

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2017 Nov 18

PMID 29145498

Citations 34

Authors

Amelia M Clark

Marta L DeDiego

Christopher S Anderson

Jiong Wang

Hongmei Yang

Aitor Nogales

Luis Martinez-Sobrido

Martin S Zand

Mark Y Sangster

David J Topham

Affiliations

Soon will be listed here.

Abstract

Antigenic drift of the hemagglutinin (HA) and neuraminidase (NA) influenza virus proteins contributes to reduced vaccine efficacy. To analyze antigenic drift in human seasonal H1N1 viruses derived from the 2009 pandemic H1N1 virus (pH1N1-like viruses) accounts for the limited effectiveness (around 40%) of vaccination against pH1N1-like viruses during the 2015-2016 season, nasal washes/swabs collected from adult subjects in the Rochester, NY area, were used to sequence and isolate the circulating viruses. The HA and NA proteins from viruses circulating during the 2015-2016 season encoded eighteen and fourteen amino acid differences, respectively, when compared to A/California/04/2009, a strain circulating at the origin of the 2009 pandemic. The circulating strains belonged to subclade 6B.1, defined by HA amino acid substitutions S101N, S179N, and I233T. Hemagglutination-inhibiting (HAI) and HA-specific neutralizing serum antibody (Ab) titers from around 50% of pH1N1-like virus-infected subjects and immune ferrets were 2-4 fold lower for the 2015-2016 circulating strains compared to the vaccine strain. In addition, using a luminex-based mPlex HA assay, the binding of human sera from subjects infected with pH1N1-like viruses to the HA proteins from circulating and vaccine strains was not identical, strongly suggesting antigenic differences in the HA protein. Additionally, NA inhibition (NAI) Ab titers in human sera from pH1N1-like virus-infected subjects increased after the infection and there were measurable antigenic differences between the NA protein of circulating strains and the vaccine strain using both ferret and human antisera. Despite having been vaccinated, infected subjects exhibited low HAI Ab titers against the vaccine and circulating strains. This suggests that poor responses to the H1N1 component of the vaccine as well as antigenic differences in the HA and NA proteins of currently circulating pH1N1-like viruses could be contributing to risk of infection even after vaccination.

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References

Salzberg S . The contents of the syringe. Nature. 2008; 454(7201):160-1. PMC: 2674578. DOI: 10.1038/454160a. View

Anderson C, DeDiego M, Thakar J, Topham D . Novel Sequence-Based Mapping of Recently Emerging H5NX Influenza Viruses Reveals Pandemic Vaccine Candidates. PLoS One. 2016; 11(8):e0160510. PMC: 4975393. DOI: 10.1371/journal.pone.0160510. View

Hensley S, Das S, Gibbs J, Bailey A, Schmidt L, Bennink J . Influenza A virus hemagglutinin antibody escape promotes neuraminidase antigenic variation and drug resistance. PLoS One. 2011; 6(2):e15190. PMC: 3043005. DOI: 10.1371/journal.pone.0015190. View

Caton A, Brownlee G, Yewdell J, GERHARD W . The antigenic structure of the influenza virus A/PR/8/34 hemagglutinin (H1 subtype). Cell. 1982; 31(2 Pt 1):417-27. DOI: 10.1016/0092-8674(82)90135-0. View

Couch R, KASEL J, Gerin J, SCHULMAN J, KILBOURNE E . Induction of partial immunity to influenza by a neuraminidase-specific vaccine. J Infect Dis. 1974; 129(4):411-20. DOI: 10.1093/infdis/129.4.411. View

Appiah G, Blanton L, DMello T, Kniss K, Smith S, Mustaquim D . Influenza activity - United States, 2014-15 season and composition of the 2015-16 influenza vaccine. MMWR Morb Mortal Wkly Rep. 2015; 64(21):583-90. PMC: 4584770. View

Petrie J, Parkhouse K, Ohmit S, Malosh R, Monto A, Hensley S . Antibodies Against the Current Influenza A(H1N1) Vaccine Strain Do Not Protect Some Individuals From Infection With Contemporary Circulating Influenza A(H1N1) Virus Strains. J Infect Dis. 2016; 214(12):1947-1951. PMC: 5142093. DOI: 10.1093/infdis/jiw479. View

Colman P, Ward C . Structure and diversity of influenza virus neuraminidase. Curr Top Microbiol Immunol. 1985; 114:177-255. DOI: 10.1007/978-3-642-70227-3_5. View

Klenk H, Garten W . Host cell proteases controlling virus pathogenicity. Trends Microbiol. 1994; 2(2):39-43. DOI: 10.1016/0966-842x(94)90123-6. View

10.

Baker S, Nogales A, Santiago F, Topham D, Martinez-Sobrido L . Competitive detection of influenza neutralizing antibodies using a novel bivalent fluorescence-based microneutralization assay (BiFMA). Vaccine. 2015; 33(30):3562-70. PMC: 4480155. DOI: 10.1016/j.vaccine.2015.05.049. View

11.

Xu R, Ekiert D, Krause J, Hai R, Crowe Jr J, Wilson I . Structural basis of preexisting immunity to the 2009 H1N1 pandemic influenza virus. Science. 2010; 328(5976):357-60. PMC: 2897825. DOI: 10.1126/science.1186430. View

12.

Virelizier J . Host defenses against influenza virus: the role of anti-hemagglutinin antibody. J Immunol. 1975; 115(2):434-9. View

13.

Anderson C, Ortega S, Chaves F, Clark A, Yang H, Topham D . Natural and directed antigenic drift of the H1 influenza virus hemagglutinin stalk domain. Sci Rep. 2017; 7(1):14614. PMC: 5668287. DOI: 10.1038/s41598-017-14931-7. View

14.

Margine I, Hai R, Albrecht R, Obermoser G, Harrod A, Banchereau J . H3N2 influenza virus infection induces broadly reactive hemagglutinin stalk antibodies in humans and mice. J Virol. 2013; 87(8):4728-37. PMC: 3624338. DOI: 10.1128/JVI.03509-12. View

15.

Kosik I, Yewdell J . Influenza A virus hemagglutinin specific antibodies interfere with virion neuraminidase activity via two distinct mechanisms. Virology. 2016; 500:178-183. PMC: 5127735. DOI: 10.1016/j.virol.2016.10.024. View

16.

Meyer A, Wilke C . Geometric Constraints Dominate the Antigenic Evolution of Influenza H3N2 Hemagglutinin. PLoS Pathog. 2015; 11(5):e1004940. PMC: 4447415. DOI: 10.1371/journal.ppat.1004940. View

17.

Nielsen R, Yang Z . Likelihood models for detecting positively selected amino acid sites and applications to the HIV-1 envelope gene. Genetics. 1998; 148(3):929-36. PMC: 1460041. DOI: 10.1093/genetics/148.3.929. View

18.

Gaymard A, Le Briand N, Frobert E, Lina B, Escuret V . Functional balance between neuraminidase and haemagglutinin in influenza viruses. Clin Microbiol Infect. 2016; 22(12):975-983. DOI: 10.1016/j.cmi.2016.07.007. View

19.

Monto A, Petrie J, Cross R, Johnson E, Liu M, Zhong W . Antibody to Influenza Virus Neuraminidase: An Independent Correlate of Protection. J Infect Dis. 2015; 212(8):1191-9. DOI: 10.1093/infdis/jiv195. View

20.

Burke D, Smith D . A recommended numbering scheme for influenza A HA subtypes. PLoS One. 2014; 9(11):e112302. PMC: 4229193. DOI: 10.1371/journal.pone.0112302. View