title: Contribution of Serologic Assays in the Evaluation of Influenza Virus Infection Rates and Vaccine Efficacy in Pregnant Women: Report From Randomized Controlled Trials.
abstract: The utility of serologic testing to evaluate vaccine efficacy of seasonal inactivated influenza vaccine (IIV) is controversial. We aimed to evaluate the efficacy of IIV against serologically diagnosed influenza infection (SDI) and reverse-transcription polymerase chain reaction-confirmed influenza illness (PCR-CI) in women vaccinated during pregnancy.
  We undertook a post hoc analysis of 2 randomized clinical trials evaluating IIV efficacy among human immunodeficiency virus (HIV)-uninfected and HIV-infected pregnant women. SDI was defined as ≥4-fold increase in paired hemagglutinin antibody inhibition titers from 1 month postvaccination until end-of-study participation. PCR-CI was defined as molecular diagnostic evidence of influenza virus in pharyngeal specimens collected during clinical illness.
  Among placebo recipients, the respective incidence of PCR-CI and SDI was 5.6% and 35.0% in HIV-uninfected women and 20.5% and 43.6% among HIV-infected women. Vaccine efficacy in HIV-uninfected women was similar for PCR-CI (66.9%; 95% confidence interval [CI], -20.1% to 90.9%) and SDI (59.2%; 95% CI, 37.0%-73.5%); however, fewer women required vaccination to prevent 1 episode of SDI (5; 95% CI, 3-9) than PCR-CI (27; 95% CI, 12-∞). Also, vaccine efficacy was similar for PCR-CI (61.2%; 95% CI, 10.7%-83.2%) and SDI (60.9%; 95% CI, 33.9%-76.9%) in HIV-infected women, with 2-fold fewer women needing to be vaccinated to prevent SDI (4; 95% CI, 3-8) than PCR-CI (8; 95% CI, 4-52).
  Although vaccine efficacy was similar when measured for PCR-CI or SDI, IIV vaccination prevented a greater number of SDI than PCR-CI; the clinical relevance of the former warrants interrogation.Clinical Trials Registration. NCT01306669 and NCT01306682.
authors.affiliation: Department of Science and Technology/National Research Foundation, Vaccine Preventable Diseases and.|Medical Research Council, Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, and.|National Institute for Communicable Diseases, National Health Laboratory Service, Centre for Vaccines and Immunology, Johannesburg, South Africa.
authors.forename: Shabir A
authors.initials: SA
authors.lastname: Madhi
authors.affiliation: Department of Science and Technology/National Research Foundation, Vaccine Preventable Diseases and.|Medical Research Council, Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, and.
authors.forename: Marta C
authors.initials: MC
authors.lastname: Nunes
authors.affiliation: School of Medicine and Children's Hospital, University of Colorado, Aurora.
authors.forename: Adriana
authors.initials: A
authors.lastname: Weinberg
authors.affiliation: Department of Science and Technology/National Research Foundation, Vaccine Preventable Diseases and.|Medical Research Council, Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, and.
authors.forename: Locadiah
authors.initials: L
authors.lastname: Kuwanda
authors.affiliation: Department of Science and Technology/National Research Foundation, Vaccine Preventable Diseases and.|Medical Research Council, Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, and.
authors.forename: Andrea
authors.initials: A
authors.lastname: Hugo
authors.affiliation: Department of Science and Technology/National Research Foundation, Vaccine Preventable Diseases and.|Medical Research Council, Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, and.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Jones
authors.affiliation: Department of Science and Technology/National Research Foundation, Vaccine Preventable Diseases and.|Medical Research Council, Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, and.
authors.forename: Nadia
authors.initials: N
authors.lastname: van Niekerk
authors.affiliation: Department of Medicine and Department of Global Health, University of Washington, Seattle.
authors.forename: Justin R
authors.initials: JR
authors.lastname: Ortiz
authors.affiliation: Center for Vaccine Development, University of Maryland, Baltimore.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Neuzil
authors.affiliation: School of Pathology, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Keith P
authors.initials: KP
authors.lastname: Klugman
authors.affiliation: Department of Pediatrics, Medicine and Pathology, University of Colorado School of Medicine, and.|Center for Global Health, Department of Epidemiology, Colorado School of Public Health, Aurora.
authors.forename: Eric A F
authors.initials: EAF
authors.lastname: Simões
authors.affiliation: Department of Science and Technology/National Research Foundation, Vaccine Preventable Diseases and.|Medical Research Council, Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, and.
authors.forename: Clare L
authors.initials: CL
authors.lastname: Cutland
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D005260:Female; D015658:HIV Infections; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D000071497:Immunogenicity, Vaccine; D007252:Influenza Vaccines / Q000008:administration & dosage*; D007251:Influenza, Human / Q000150:complications / Q000175:diagnosis* / Q000453:epidemiology / Q000517:prevention & control*; D009975:Orthomyxoviridae / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000175:diagnosis* / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014611:Vaccination; D015164:Vaccines, Inactivated / Q000008:administration & dosage
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated
keywords: efficacy; hemagglutination inhibition assay.; immunogenicity; influenza vaccine; phase III trial