TY - JOUR
T1 - Predictors of oral rotavirus vaccine immunogenicity in rural Zimbabwean infants
AU - Church, James A.
AU - Chasekwa, Bernard
AU - Rukobo, Sandra
AU - Govha, Margaret
AU - Lee, Benjamin
AU - Carmolli, Marya P.
AU - Ntozini, Robert
AU - Mutasa, Kuda
AU - McNeal, Monica M.
AU - Majo, Florence D.
AU - Tavengwa, Naume V.
AU - Kirkpatrick, Beth D.
AU - Moulton, Lawrence H.
AU - Humphrey, Jean H.
AU - Prendergast, Andrew J.
N1 - Funding Information:
This work was supported by the Wellcome Trust [203905/Z/16/Z to JAC and 093768/Z/10/Z and 108065/Z/15/Z to AJP]. The SHINE trial was funded by the Bill and Melinda Gates Foundation [OPP1021542 and OPP113707]; UK Department for International Development (UK Aid); Swiss Agency for Development and Cooperation and US National Institutes of Health [2R01HD060338-06]. The study funders approved the trial design, but were not involved in data collection, analysis, interpretation, or manuscript preparation. The corresponding author had full access to the data and took the decision to submit for publication.
Funding Information:
This work was supported by the Wellcome Trust [ 203905/Z/16/Z to JAC and 093768/Z/10/Z and 108065/Z/15/Z to AJP]. The SHINE trial was funded by the Bill and Melinda Gates Foundation [ OPP1021542 and OPP113707 ]; UK Department for International Development (UK Aid); Swiss Agency for Development and Cooperation and US National Institutes of Health [ 2R01HD060338-06 ]. The study funders approved the trial design, but were not involved in data collection, analysis, interpretation, or manuscript preparation. The corresponding author had full access to the data and took the decision to submit for publication.
Publisher Copyright:
© 2020 The Authors
PY - 2020/3/17
Y1 - 2020/3/17
N2 - Background: Oral rotavirus vaccines (RVV) have poor immunogenicity in low-income countries, for reasons that remain unclear. This study identified the determinants of RVV immunogenicity among infants in rural Zimbabwe. Methods: Anti-rotavirus IgA titres were measured among a sub-group of infants enrolled in the Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial (NCT01824940). SHINE was a cluster-randomized trial of improved infant and young child feeding, and improved water, sanitation and hygiene (WASH) in two rural Zimbabwean districts. Infants received RVV as part of the national immunisation programme. Among HIV-unexposed infants in the non-WASH trial arms, we evaluated associations between potential risk factors (vaccine schedule and dose, maternal and infant nutritional status, infant diarrhoea, and household environment) and RVV immunogenicity (seroconversion, seropositivity and geometric mean titres) using multivariable regression. Results: Among 219 infants with seroconversion data, 43 (20%) successfully seroconverted and 176 (80%) failed to seroconvert to RVV. Seroconversion was positively associated with a higher length-for-age Z-score (LAZ) around the time of vaccination (adjusted RR 1.27 (95% CI 1.04, 1.55), P = 0.021), and negatively associated with concurrent OPV and RVV administration (adjusted RR 0.36 (0.19, 0.71), P = 0.003). Among 472 infants with post-vaccination titres, a higher LAZ score was associated with increased seropositivity (aRR 1.21 (95% CI 1.06, 1.38), P = 0.004), and higher birthweight was associated with increased IgA titres (0.45 (95%CI 0.18, 1.09) U/mL greater per 100 g gain in birthweight; P = 0.001). Conclusions: Infant ponderal and linear growth were positively associated with RVV immunogenicity, while concurrent administration of OPV was negatively associated with RVV immunogenicity. Together, these findings suggest that improving foetal growth and separating RVV and OPV administration are plausible approaches to increasing RVV immunogenicity.
AB - Background: Oral rotavirus vaccines (RVV) have poor immunogenicity in low-income countries, for reasons that remain unclear. This study identified the determinants of RVV immunogenicity among infants in rural Zimbabwe. Methods: Anti-rotavirus IgA titres were measured among a sub-group of infants enrolled in the Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial (NCT01824940). SHINE was a cluster-randomized trial of improved infant and young child feeding, and improved water, sanitation and hygiene (WASH) in two rural Zimbabwean districts. Infants received RVV as part of the national immunisation programme. Among HIV-unexposed infants in the non-WASH trial arms, we evaluated associations between potential risk factors (vaccine schedule and dose, maternal and infant nutritional status, infant diarrhoea, and household environment) and RVV immunogenicity (seroconversion, seropositivity and geometric mean titres) using multivariable regression. Results: Among 219 infants with seroconversion data, 43 (20%) successfully seroconverted and 176 (80%) failed to seroconvert to RVV. Seroconversion was positively associated with a higher length-for-age Z-score (LAZ) around the time of vaccination (adjusted RR 1.27 (95% CI 1.04, 1.55), P = 0.021), and negatively associated with concurrent OPV and RVV administration (adjusted RR 0.36 (0.19, 0.71), P = 0.003). Among 472 infants with post-vaccination titres, a higher LAZ score was associated with increased seropositivity (aRR 1.21 (95% CI 1.06, 1.38), P = 0.004), and higher birthweight was associated with increased IgA titres (0.45 (95%CI 0.18, 1.09) U/mL greater per 100 g gain in birthweight; P = 0.001). Conclusions: Infant ponderal and linear growth were positively associated with RVV immunogenicity, while concurrent administration of OPV was negatively associated with RVV immunogenicity. Together, these findings suggest that improving foetal growth and separating RVV and OPV administration are plausible approaches to increasing RVV immunogenicity.
KW - Africa
KW - Immunogenicity
KW - Infants
KW - Oral vaccine
KW - Rotavirus
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U2 - 10.1016/j.vaccine.2020.01.097
DO - 10.1016/j.vaccine.2020.01.097
M3 - Article
C2 - 32088018
AN - SCOPUS:85079905961
VL - 38
SP - 2870
EP - 2878
JO - Vaccine
JF - Vaccine
SN - 0264-410X
IS - 13
ER -