Rotavirus specific maternal antibodies and immune response to RV3-BB neonatal rotavirus vaccine in New Zealand

Abstract

Background: Maternal antibodies, acquired passively via placenta and/or breast milk, may contribute to the reduced efficacy of oral rotavirus vaccines 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 rotavirus vaccine, RV3-BB, in parallel to a Phase IIa clinical trial conducted at Dunedin Hospital, New Zealand. At the time of the study rotavirus vaccines had not been introduced in New Zealand and the burden of rotavirus disease was evident.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 randomized to receive the first dose of vaccine at 0-5 d (neonatal schedule) or 8 weeks (infant schedule). Breast feeding was with-held for 30 minutes before and after vaccine administration. The relationship between rotavirus specific IgG and SNA levels in cord blood and IgA in colostrum and breast milk at the time of first active dose of RV3-BB vaccine and level of IgA response and stool excretion after 3 doses of vaccine was assessed using linear and logistic regression.Results: Forty infants received 3 doses of RV3-BB rotavirus vaccine and were included in the analysis of the neonatal and infant groups. Rotavirus specific IgA in colostrum (neonatal schedule group) and breast milk at 4 weeks (infant schedule group) was identified in 14/21 (67%) and 14/17 (82%) of infants respectively. There was little evidence of an association between IgA in colostrum or breast milk IgA at 4 weeks, or between cord IgG or SNA level, and IgA response or stool excretion after 3 doses of RV3-BB, or after one dose (neonatal schedule) (all p>0.05).Conclusions: The level of IgA in colostrum or breast milk and level of placental IgG and SNA did not impact on the serum IgA response or stool excretion following 3 doses of RV3-BB Rotavirus Vaccine administered using either a neonatal or infant schedule in New Zealand infants.

Differences of Rotavirus Vaccine Effectiveness by Country: Likely Causes and Contributing Factors

“…Studies from Nicaragua [ 101 ], India [ 99 , 102 ] and South Africa [ 103 ] demonstrated that mother’s RV-specific IgG levels before RV vaccination of their infants was negatively associated with infants’ seroconversion after RV vaccination. A similar trend observed for vaccines in New Zealand lacked significance [ 104 ].…”

Rotavirus infection

“…As asymptomatic infections with specific rotavirus strains in neonates are associated with protection against disease later in life, vaccines based on these strains have been developed. These include ROTAVAC (Bharat Biotech), which is based on rotavirus strain 116E and is now licensed in India 132 and RV3 (PT Bio Farma, Indonesia/Murdoch Children’s Research Institute, Australia), which was developed in Australia and is in clinical trials in neonates and infants 133 . Other live oral vaccines include the Lanzhou lamb rotavirus vaccine in China (Lanzhou Institute of Biological Products, China) and the Rotavin-M1 (Center for Research and Production of Vaccines and Biologicals) attenuated human vaccine in Vietnam 90 .…”

Serological responses to rotavirus NSP2 following administration of RV3-BB human neonatal rotavirus vaccine

“…We have previously demonstrated that cord blood anti-rotavirus IgG did not impact the serum IgA response or stool excretion after 3 doses of RV3-BB or after one dose. 22 This suggests limited impact of the anti-NSP2 IgG antibodies on the RV3-BB vaccine immune responses. However, the role of these maternally derived anti-NPS2 IgG antibodies in the immunity to wild-type rotavirus infections in the newborn remains to be elucidated.…”