Article: High titer and avidity of nonneutralizing antibodies against influenza vaccine antigen are associated with severe influenza

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TitleHigh titer and avidity of nonneutralizing antibodies against influenza vaccine antigen are associated with severe influenza
AuthorsTo, KKW
Zhang, AJX
Hung, IFN
Xu, T
Ip, WCT
Wong, RTY
Ng, JCK
Chan, JFW
Chan, KH
Yuen, KY
Issue Date2012
PublisherAmerican Society for Microbiology. The Journal's web site is located at http://cdli.asm.org/
CitationClinical And Vaccine Immunology, 2012, v. 19 n. 7, p. 1012-1018 [How to Cite?]
DOI: http://dx.doi.org/10.1128/CVI.00081-12
AbstractThe importance of neutralizing antibody in protection against influenza virus is well established, but the role of the early antibody response during the initial stage of infection in affecting the severity of disease is unknown. The 2009 influenza pandemic provided a unique opportunity for study because most patients lacked preexisting neutralizing antibody. In this study, we compared the antibody responses of 52 patients with severe or mild disease, using sera collected at admission. A microneutralization (MN) assay was used to detect neutralizing antibody. We also developed an enzyme-linked immunosorbent assay (ELISA) which detects both neutralizing and nonneutralizing antibodies against viral antigens from a split-virion inactivated monovalent influenza virus vaccine. While the MN titers were not significantly different between the two groups (P = 0.764), the ELISA titer and ELISA/MN titer ratio were significantly higher for patients with severe disease than for those with mild disease (P = 0.004 and P = 0.011, respectively). This finding suggested that in patients with severe disease, a larger proportion of serum antibodies were antibodies with no detectable neutralizing activity. The antibody avidity was also significantly higher in patients with severe disease than in those with mild disease (P < 0.05). Among patients with severe disease, those who required positive pressure ventilation (PPV) had significantly higher ELISA titers than those who did not require PPV (P < 0.05). Multivariate analysis showed that the ELISA titer and antibody avidity were independently associated with severe disease. Higher titers of nonneutralizing antibody with higher avidity at the early stage of influenza virus infection may be associated with worse clinical severity and poorer outcomes. Copyright © 2012, American Society for Microbiology. All Rights Reserved.
ISSN1556-6811
2011 Impact Factor: 2.546
2011 SCImago Journal Rankings: 0.248
DOIhttp://dx.doi.org/10.1128/CVI.00081-12
PubMed Central IDPMC3393364
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorTo, KKW
dc.contributor.authorZhang, AJX
dc.contributor.authorHung, IFN
dc.contributor.authorXu, T
dc.contributor.authorIp, WCT
dc.contributor.authorWong, RTY
dc.contributor.authorNg, JCK
dc.contributor.authorChan, JFW
dc.contributor.authorChan, KH
dc.contributor.authorYuen, KY
dc.date.accessioned2012-09-05T05:32:44Z
dc.date.available2012-09-05T05:32:44Z
dc.date.issued2012
dc.description.abstractThe importance of neutralizing antibody in protection against influenza virus is well established, but the role of the early antibody response during the initial stage of infection in affecting the severity of disease is unknown. The 2009 influenza pandemic provided a unique opportunity for study because most patients lacked preexisting neutralizing antibody. In this study, we compared the antibody responses of 52 patients with severe or mild disease, using sera collected at admission. A microneutralization (MN) assay was used to detect neutralizing antibody. We also developed an enzyme-linked immunosorbent assay (ELISA) which detects both neutralizing and nonneutralizing antibodies against viral antigens from a split-virion inactivated monovalent influenza virus vaccine. While the MN titers were not significantly different between the two groups (P = 0.764), the ELISA titer and ELISA/MN titer ratio were significantly higher for patients with severe disease than for those with mild disease (P = 0.004 and P = 0.011, respectively). This finding suggested that in patients with severe disease, a larger proportion of serum antibodies were antibodies with no detectable neutralizing activity. The antibody avidity was also significantly higher in patients with severe disease than in those with mild disease (P < 0.05). Among patients with severe disease, those who required positive pressure ventilation (PPV) had significantly higher ELISA titers than those who did not require PPV (P < 0.05). Multivariate analysis showed that the ELISA titer and antibody avidity were independently associated with severe disease. Higher titers of nonneutralizing antibody with higher avidity at the early stage of influenza virus infection may be associated with worse clinical severity and poorer outcomes. Copyright © 2012, American Society for Microbiology. All Rights Reserved.
dc.description.naturelink_to_OA_fulltext
dc.identifier.citationClinical And Vaccine Immunology, 2012, v. 19 n. 7, p. 1012-1018 [How to Cite?]
DOI: http://dx.doi.org/10.1128/CVI.00081-12
dc.identifier.doihttp://dx.doi.org/10.1128/CVI.00081-12
dc.identifier.epage1018
dc.identifier.hkuros203192
dc.identifier.issn1556-6811
2011 Impact Factor: 2.546
2011 SCImago Journal Rankings: 0.248
dc.identifier.issue7
dc.identifier.pmcidPMC3393364
dc.identifier.pmid22573737
dc.identifier.scopuseid_2-s2.0-84863558273
dc.identifier.spage1012
dc.identifier.urihttp://hdl.handle.net/10722/163507
dc.identifier.volume19
dc.languageeng
dc.publisherAmerican Society for Microbiology. The Journal's web site is located at http://cdli.asm.org/
dc.publisher.placeUnited States
dc.relation.ispartofClinical and Vaccine Immunology
dc.relation.referencesReferences in Scopus
dc.rightsClinical and Vaccine Immunology. Copyright © American Society for Microbiology.
dc.rightsCopyright © American Society for Microbiology, [Clinical and Vaccine Immunology, 2012, v. 19 n. 7, p. 1012-1018]
dc.subject.meshAntibodies, Neutralizing - blood
dc.subject.meshAntibodies, Viral - blood
dc.subject.meshAntibody Affinity
dc.subject.meshInfluenza A Virus, H1N1 Subtype - immunology
dc.subject.meshInfluenza, Human - immunology - pathology - virology
dc.titleHigh titer and avidity of nonneutralizing antibodies against influenza vaccine antigen are associated with severe influenza
dc.typeArticle
Author Affiliations
  1. The University of Hong Kong