title: Association of Maternal Immunity with Rotavirus Vaccine Immunogenicity in Zambian Infants.
abstract: BACKGROUND
  Live attenuated oral vaccines against rotavirus (RV) have been shown to be less efficacious in children from developing countries. Reasons for this disparity are not fully understood. We assessed the role of maternal factors including breast milk RV-specific IgA, transplacentally acquired infant serum RV-specific IgG and maternal HIV status in seroconversion among Zambian infants routinely immunized with Rotarix™ (RV1).
  
  
  METHODS
  420 mother-child pairs were recruited at infant age 6-12 weeks in Lusaka. Clinical information and samples were collected at baseline and at one month following the second dose of RV1. Determination of breast milk RV-specific IgA and serum RV-specific IgA and IgG was done using standardized ELISA. Seroconversion was defined as a ≥ 4 fold rise in serum IgA titre from baseline to one-month post RV1 dose 2, while seropositivity of IgA was defined as serum titre ≥ 40 and antibody variables were modelled on log-base 2. Logistic regression was used to identify predictors of the odds of seroconversion.
  
  
  RESULTS
  Baseline infant seropositivity was 25.5% (91/357). The seroconversion frequency was 60.2% (130/216). Infants who were IgA seropositive at baseline were less likely to seroconvert compared to their seronegative counterparts (P = 0.04). There was no evidence of an association between maternal HIV status and seroconversion (P = 0.25). Higher titres of breast milk rotavirus-specific IgA were associated with a lower frequency of seroconverson (Nonparametric test for trend Z = -2.84; P<0.01): a two-fold increase in breast milk RV-specific IgA titres was associated with a 22% lower odds of seroconversion (OR = 0.80; 95% CI = 0.68-0.94; P = 0.01). There was seasonal variation in baseline breast milk rotavirus-specific IgA titres, with significantly higher GMTs during the cold dry months (P = 0.01).
  
  
  CONCLUSIONS
  Low immunogenicity of RV1 vaccine could be explained in part by exposure to high antibody titres in breast milk and early exposure to wild-type rotavirus infections. Potential interference of anti-RV specific IgA in breast milk and pre-vaccination serum RV specific-IgA and IgG titres with RV1 seroconversion and effectiveness requires further research.
authors.affiliation: Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.|University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Roma
authors.initials: R
authors.lastname: Chilengi
authors.affiliation: Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.
authors.forename: Michelo
authors.initials: M
authors.lastname: Simuyandi
authors.affiliation: Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.
authors.forename: Lauren
authors.initials: L
authors.lastname: Beach
authors.affiliation: Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.
authors.forename: Katayi
authors.initials: K
authors.lastname: Mwila
authors.affiliation: University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Becker-Dreps
authors.affiliation: Centres for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Devy M
authors.initials: DM
authors.lastname: Emperador
authors.affiliation: Centres for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Velasquez
authors.affiliation: Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.
authors.forename: Samuel
authors.initials: S
authors.lastname: Bosomprah
authors.affiliation: Centres for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Baoming
authors.initials: B
authors.lastname: Jiang
mesh_terms: D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D001942:Breast Feeding; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D012400:Rotavirus Infections / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D022243:Rotavirus Vaccines / Q000008:administration & dosage*; D014613:Vaccines, Attenuated / Q000008:administration & dosage; D015024:Zambia
chemical_list: D000914:Antibodies, Viral; D007070:Immunoglobulin A; D007074:Immunoglobulin G; C492457:RIX4414 vaccine; D022243:Rotavirus Vaccines; D014613:Vaccines, Attenuated