title: Prevaccination Rotavirus Serum IgG and IgA Are Associated With Lower Immunogenicity of Live, Oral Human Rotavirus Vaccine in South African Infants.
abstract: BACKGROUND
  Live oral rotavirus (RV) vaccines have shown modest efficacy among children in African countries for reasons that are not completely understood. We examined the possible inhibitory effect of preexisting antirotavirus antibodies on immunogenicity of monovalent RV vaccine (RV1).
  
  
  METHODS
  Mother-infant pairs were enrolled at presentation for their routine immunization visit in Soweto, South Africa, when infants were aged 5-8 weeks. Infant serum samples were obtained before the first and second doses of RV1 and 1 month after the second dose. Maternal serum and breast milk samples were obtained prior to administration of each dose of RV1 to infants. RV-specific immunoglobulin G (IgG), IgA, and neutralizing activity in sera of infants and serum or breast milk samples of mothers were measured using enzyme-linked immunosorbent assays or a microneutralization test.
  
  
  RESULTS
  Of the 107 serum pairs from infants who were seronegative for RV IgA at enrollment, we observed a strong positive association between IgG titers in pre-dose 1 sera of infants and mothers and significant negative associations between IgG titers in pre-dose 1 sera of infants and seroconversion to RV1 post-dose 1. Similarly, mothers whose infants' IgA seroconverted after RV1 had significantly lower pre-dose 1 IgG titers in sera than those whose infants did not seroconvert.
  
  
  CONCLUSIONS
  High levels of preexisting serum IgG, including transplacentally acquired maternal IgG, appeared to have an inhibitory effect on the immunogenicity of RV1 among infants and may, in part, contribute to lower efficacy of RV vaccines in this and other low-income settings.
authors.affiliation: Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Sung-Sil
authors.initials: SS
authors.lastname: Moon
authors.affiliation: Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, Johannesburg.
authors.forename: Michelle J
authors.initials: MJ
authors.lastname: Groome
authors.affiliation: Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Velasquez
authors.affiliation: Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Umesh D
authors.initials: UD
authors.lastname: Parashar
authors.affiliation: Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, Johannesburg.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Jones
authors.affiliation: Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, Johannesburg.
authors.forename: Antoinette
authors.initials: A
authors.lastname: Koen
authors.affiliation: Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, Johannesburg.
authors.forename: Nadia
authors.initials: N
authors.lastname: van Niekerk
authors.affiliation: Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Baoming
authors.initials: B
authors.lastname: Jiang
authors.affiliation: Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, Johannesburg National Institute for Communicable Diseases: National Health Laboratory Service, Centre for Vaccines and Immunology, Sandringham, South Africa.
authors.forename: Shabir A
authors.initials: SA
authors.lastname: Madhi
mesh_terms: D000284:Administration, Oral; D057134:Antibodies, Neutralizing / Q000032:analysis; D000914:Antibodies, Viral / Q000032:analysis*; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis*; D007074:Immunoglobulin G / Q000032:analysis*; D007223:Infant; D008895:Milk, Human / Q000276:immunology; D012401:Rotavirus / Q000276:immunology*; D012400:Rotavirus Infections / Q000517:prevention & control*; D022243:Rotavirus Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D044967:Serum / Q000276:immunology; D013019:South Africa; D016896:Treatment Outcome; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007070:Immunoglobulin A; D007074:Immunoglobulin G; C492457:RIX4414 vaccine; D022243:Rotavirus Vaccines; D014613:Vaccines, Attenuated
keywords: Rotarix; breast milk; rotavirus; transplacental antibody