title: A systematic review of anti-rotavirus serum IgA antibody titer as a potential correlate of rotavirus vaccine efficacy.
abstract: BACKGROUND
  Identifying an immunological correlate of protection for rotavirus vaccines (Rotarix [RV1] and RotaTeq [RV5]) would substantially facilitate testing of interventions for improving efficacy in developing countries and evaluating additional candidate rotavirus vaccines.
  
  
  METHODS
  We accessed PubMed and ClinicalTrials.gov to identify immunogenicity and efficacy trials for RV1 and RV5 to correlate anti-rotavirus serum immunoglobulin A (IgA) antibody titers vs efficacy in regions stratified by all-cause under-5 mortality rates (u5MR). We established a cutoff point for IgA geometric mean concentration or titer (GMC) that predicted lower efficacy and calculated pooled vaccine efficacy among countries with high vs low IgA titers.
  
  
  RESULTS
  We observed an inverse correlation between u5MR and IgA titers for RV1 (r(2) = 0.72; P < .001 and RV5 (r(2) = 0.66; P < .001) and between efficacy and IgA titers for both vaccines (r(2) = 0.56; P = .005). Postimmunization anti-rotavirus IgA GMC <90 were associated with decline in vaccine efficacy. Efficacy during first 2 years of life was significantly lower among countries with IgA GMC < 90 (44%; 95% confidence interval [CI], 30-55) compared to countries with GMC > 90 (85%; 95% CI, 82-88).
  
  
  CONCLUSIONS
  We observed a significant correlation between IgA titers and rotavirus vaccine efficacy and hypothesize that a critical level of IgA antibody titer is associated with a sufficient level of sustained protection after rotavirus vaccination.
authors.affiliation: National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA. mpatel@cdc.gov
authors.forename: Manish
authors.initials: M
authors.lastname: Patel
authors.forename: Roger I
authors.initials: RI
authors.lastname: Glass
authors.forename: Baoming
authors.initials: B
authors.lastname: Jiang
authors.forename: Mathuram
authors.initials: M
authors.lastname: Santosham
authors.forename: Ben
authors.initials: B
authors.lastname: Lopman
authors.forename: Umesh
authors.initials: U
authors.lastname: Parashar
mesh_terms: D000914:Antibodies, Viral / Q000097:blood; D000917:Antibody Formation / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology*; D012401:Rotavirus / Q000276:immunology*; D012400:Rotavirus Infections / Q000276:immunology* / Q000517:prevention & control*; D022243:Rotavirus Vaccines / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D007070:Immunoglobulin A; C492457:RIX4414 vaccine; C492535:RotaTeq; D022243:Rotavirus Vaccines; D014613:Vaccines, Attenuated
keywords: antibody; diarrhea; efficacy; immunity; protection; rotavirus; vaccines