Rotavirus Specific Maternal Antibodies and Immune Response to RV3-BB Neonatal Rotavirus Vaccine in New Zealand
Background: Rotavirus specific maternal antibodies acquired passively via placental and/or breast milk may contribute to the reduced oral rotavirus vaccine efficacy observed in children in developing countries. This study aimed to investigate the effect of rotavirus specific maternal antibodies on the serum IgA response or stool excretion of vaccine virus after any dose of an oral neonatal rotavirus vaccine, RV3-BB, in parallel to a Phase IIa clinical trial conducted at Dunedin Hospital, New Zealand.Methods: Rotavirus specific IgG and serum neutralizing antibody (SNA) levels in cord blood and IgA levels in colostrum and breast milk samples collected ~4 weeks, ~20 weeks and ~28 weeks after birth were measured. Infants were randomised to receive the first dose of vaccine at 0–5 days after birth (neonatal schedule) or at 8 weeks (infant schedule). Breast feeding was with-held for 30 minutes before and after vaccine administration. Data for IgA response and stool vaccine virus excretion after RV3-BB rotavirus vaccine was obtained from the Phase IIa clinical trial. The relationship between rotavirus specific IgA in colostrum or breast milk at the time of first active dose of RV3-BB vaccine and rotavirus specific IgG and SNA levels in cord blood, and level of IgA response and stool vaccine virus excretion after three doses of vaccine was assessed using linear and logistic regression. The relationship between rotavirus specific IgA in colostrum and rotavirus specific IgG a nd SNA levels in cord blood, and level of IgA response and stool vaccine virus excretion after a single neonatal dose of vaccine in the neonatal schedule group was also assessed.Results: Twenty one infants in the neonatal schedule group and 19 infants in the infant schedule group received 3 doses of RV3-BB rotavirus vaccine and were included in the analysis. Rotavirus specific IgA in colostrum and breast milk at 4 weeks was identified in 14/21 (67%) and 14/17 (82%) of infants in the neonatal and infant schedule groups respectively. IgA responses after 3 doses were identified in 76% and 74% of infants in the neonatal and infant groups, stool excretion of vaccine virus in 71% and 79% of infants. There was no evidence of an association between IgA in colostrum or breast milk IgA at 4 weeks and IgA response or stool excretion after three doses of RV3-BB, or after one dose (neonatal schedule). There was little evidence of an association between cord IgG or SNA level and level of IgA response and stool excretion after one neonatal dose or after 3 doses of RV3-BB.Conclusions: The level of IgA in colostrum or breast milk and placental IgG and SNA did not affect the serum IgA response or stool excretion following three doses of RV3-BB Rotavirus Vaccine administered using a neonatal or infant schedule in New Zealand infants.
Advisor: Broadbent, Roland
Degree Name: Master of Medical Science
Degree Discipline: Department of Women's and Children's Health
Publisher: University of Otago
Keywords: rotavirus; maternal antibodies; rotavirus vaccine
Research Type: Thesis