Abstract
BackgroundNutritional status may play a role in infant immune development. To identify potential boosters of immunogenicity in low-income countries where oral vaccine efficacy is low, we tested the effect of prenatal nutritional supplementation on immune response to 3 doses of a live oral rotavirus vaccine.Methods and findingsWe nested a cluster randomized trial within a double-blind, placebo-controlled randomized efficacy trial to assess the effect of 3 prenatal nutritional supplements (lipid-based nutrient supplement [LNS], multiple micronutrient supplement [MMS], or iron–folic acid [IFA]) on infant immune response (n = 53 villages and 1,525 infants with valid serology results: 794 in the vaccine group and 731 in the placebo group). From September 2015 to February 2017, participating women received prenatal nutrient supplement during pregnancy. Eligible infants were then randomized to receive 3 doses of an oral rotavirus vaccine or placebo at 6–8 weeks of age (mean age: 6.3 weeks, 50% female). Infant sera (pre-Dose 1 and 28 days post-Dose 3) were analyzed for anti-rotavirus immunoglobulin A (IgA) using enzyme-linked immunosorbent assay (ELISA). The primary immunogenicity end point, seroconversion defined as ≥3-fold increase in IgA, was compared in vaccinated infants among the 3 supplement groups and between vaccine/placebo groups using mixed model analysis of variance procedures. Seroconversion did not differ by supplementation group (41.1% (94/229) with LNS vs. 39.1% (102/261) with multiple micronutrients (MMN) vs. 38.8% (118/304) with IFA, p = 0.91). Overall, 39.6% (n = 314/794) of infants who received vaccine seroconverted, compared to 29.0% (n = 212/731) of infants who received placebo (relative risk [RR]: 1.36; 95% confidence interval [CI]: 1.18, 1.57, p < 0.001). This study was conducted in a high rotavirus transmission setting. Study limitations include the absence of an immune correlate of protection for rotavirus vaccines, with the implications of using serum anti-rotavirus IgA for the assessment of immunogenicity and efficacy in low-income countries unclear.ConclusionsThis study showed no effect of the type of prenatal nutrient supplementation on immune response in this setting. Immune response varied depending on previous exposure to rotavirus, suggesting that alternative delivery modalities and schedules may be considered to improve vaccine performance in high transmission settings.Trial registrationClinicalTrials.gov NCT02145000.
Highlights
Oral vaccines offer several advantages over parenteral vaccines: They can be produced in large quantities at low cost, are easy to administer, and can effectively induce local immunity in the intestinal mucosa to block disease transmission [1]
This study showed no effect of the type of prenatal nutrient supplementation on immune response in this setting
Immune response varied depending on previous exposure to rotavirus, suggesting that alternative delivery modalities and schedules may be considered to improve vaccine performance in high transmission settings
Summary
Oral vaccines offer several advantages over parenteral vaccines: They can be produced in large quantities at low cost, are easy to administer, and can effectively induce local immunity in the intestinal mucosa to block disease transmission [1]. The impact of oral rotavirus vaccines was swiftly shown following introduction in national immunization programs with demonstrated reductions in rotavirus disease, hospital admissions, and mortality [2]. Oral vaccines in general are only half as effective in low-income countries, where child mortality is high, and disease burden is greatest, compared to high-income countries. This gap in oral vaccine efficacy was first observed in the 1950s with the introduction of the oral polio vaccine (OAPVU):[3P]leaansdenhoastebtheaentthoebasbebrvredviafotiroontOhePrVlihvaesobreaelnvianctrcoindeuscesudcfohraosratylppohloioidvaccineint and cholera [4,5]. Oral rotavirus vaccines are 85% to 98% efficacious against severe rotavirus gastroenteritis (SRVGE) among North American and European infants [6,7] but only 40% to 64% in sub-Saharan Africa [8,9,10]
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