title: Differential profiles and inhibitory effect on rotavirus vaccines of nonantibody components in breast milk from mothers in developing and developed countries.
abstract: BACKGROUND
  Live oral rotavirus vaccines have been less immunogenic and efficacious for children of developing countries than for those in middle income and industrialized countries, and the basis for these differences is not fully understood. Recently, we demonstrated that breastmilk from mothers in India had significantly higher IgA and neutralizing activity against rotavirus that could reduce the effective titer of rotavirus vaccines reaching the gut when compared with that from mothers in the United States. We extended our study to understand the specific contribution of those nonantibody components in breastmilk to the neutralizing activity against rotavirus vaccine we observed.
  
  
  METHODS
  Breastmilk samples were collected from mothers of breast-feeding infants aged between 4 and 29 weeks (ie, vaccine eligible age) in India (N = 40), South Africa (N = 50) and the United States (N = 51). We examined breastmilk for lactoferrin, lactadherin, rotavirus-specific IgA and neutralizing activity against 3 rotavirus vaccine strains (Rotarix, RotaTeq G1 and 116E) using enzyme immunoassays, a plaque reduction assay or a microneutralization assay.
  
  
  RESULTS
  We observed higher levels of lactoferrin, lactadherin, IgA and neutralizing activity in breastmilk specimens from Indian and South African women than those from American women. We demonstrated positive associations between levels of lactoferrin or IgA and neutralizing activity in Indian and South African specimens, but not in American specimens. We demonstrated that the inhibitory effect of lactoferrin was dose- or species-dependent, as evidenced by greater reduction in titer of Rotarix and 116E by human lactoferrin. Lactadherin also exhibited inhibitory activity to rotavirus vaccines but appeared to be less effective.
  
  
  CONCLUSIONS
  The lower immunogenicity and efficacy of rotavirus vaccines in developing countries could be explained, in part, by synergistic inhibitory effect of high levels of antibody and nonantibody components in breastmilk consumed by infants at the time of immunization. Therefore, there is a need for alternative rotavirus vaccine strategies in breast-feeding populations.
authors.affiliation: Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Sung-Sil
authors.initials: SS
authors.lastname: Moon
authors.forename: Jacqueline E
authors.initials: JE
authors.lastname: Tate
authors.forename: Pratima
authors.initials: P
authors.lastname: Ray
authors.forename: Penelope H
authors.initials: PH
authors.lastname: Dennehy
authors.forename: Derseree
authors.initials: D
authors.lastname: Archary
authors.forename: Anna
authors.initials: A
authors.lastname: Coutsoudis
authors.forename: Ruth
authors.initials: R
authors.lastname: Bland
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Newell
authors.forename: Roger I
authors.initials: RI
authors.lastname: Glass
authors.forename: Umesh
authors.initials: U
authors.lastname: Parashar
authors.forename: Baoming
authors.initials: B
authors.lastname: Jiang
mesh_terms: D000293:Adolescent; D000328:Adult; D057134:Antibodies, Neutralizing / Q000032:analysis / Q000276:immunology; D000914:Antibodies, Viral / Q000032:analysis / Q000276:immunology*; D019049:Developed Countries / Q000706:statistics & numerical data; D003906:Developing Countries / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis / Q000276:immunology; D007194:India; D008894:Milk Proteins / Q000032:analysis / Q000276:immunology*; D008895:Milk, Human / Q000737:chemistry / Q000187:drug effects* / Q000276:immunology*; D009500:Neutralization Tests; D012044:Regression Analysis; D012401:Rotavirus / Q000276:immunology*; D022243:Rotavirus Vaccines / Q000008:administration & dosage*; D013019:South Africa; D018709:Statistics, Nonparametric; D014481:United States
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007070:Immunoglobulin A; D008894:Milk Proteins; D022243:Rotavirus Vaccines