Investigating barriers to the protective efficacy provided by rotavirus vaccines in African infants
| Autor: | Rebecca F. Grais, Iza Ciglenecki, Céline Langendorf, Monica M. McNeal, Ousmane Guindo, Eric Adehossi, Souna Garba, Brian D. Plikaytis, Sheila Isanaka |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
RNA viruses Rotavirus Viral Diseases Physiology medicine.disease_cause Pathology and Laboratory Medicine Biochemistry law.invention Families Immunogenicity Vaccine Medical Conditions Randomized controlled trial Pregnancy law Reoviruses Immune Physiology Medicine and Health Sciences Cluster Analysis Public and Occupational Health Micronutrients Niger Prenatal Nutritional Physiological Phenomena Children Immune Response Vaccines Immune System Proteins Immunogenicity General Medicine Lipids Rotavirus vaccine Vaccination and Immunization Infectious Diseases Medical Microbiology Viral Pathogens Viruses Medicine Female Pathogens Infants Research Article medicine.medical_specialty Nutritional Supplementation Infectious Disease Control Iron Immunology Vaccines Attenuated Placebo Microbiology Rotavirus Infections Folic Acid Double-Blind Method Internal medicine Vaccine Development medicine Humans Seroconversion Antigens Microbial Pathogens Rotavirus Infection Biology and life sciences business.industry Rotavirus Vaccines Organisms Infant Proteins Vaccine efficacy Age Groups Dietary Supplements People and Places Population Groupings Preventive Medicine business |
| Zdroj: | PLoS Medicine, Vol 18, Iss 8 (2021) PLoS Medicine, Vol 18, Iss 8, p e1003720 (2021) PLoS Medicine |
| Popis: | Background Nutritional 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 findings We 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. Conclusions 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. Trial registration ClinicalTrials.gov NCT02145000. Sheila Isanaka and co-workers study nutrient supplementation and infants’ immune responses to rotavirus vaccination. Author summary Why was this study done? The World Health Organization recommends that all children be vaccinated against rotavirus, the most common cause of severe childhood diarrhea and a major cause of morbidity and mortality worldwide. Two oral rotavirus vaccines have been shown to be highly efficacious against childhood diarrhea in high- and middle-income countries (85%–98%), but, virtually, all trials in sub-Saharan Africa and South Asia have shown lower immune response and much lower efficacy (40%–64%), leaving many children unprotected. As the development of the immune cells that support vaccine response specifically depend on an adequate supply of micronutrients, nutritional supplementation has been considered as a potential adjunctive intervention to improve oral vaccine performance. What did the researchers do and find? We 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. This study found no effect of the type of prenatal nutrient supplementation on immune response in this setting; however, the immune response appeared to vary by previous exposure to rotavirus. What do these findings mean? To improve the oral vaccine immunogenicity gap between low- and high-income countries, a more complete understanding of the factors influencing immunogenicity and a reliable correlate of protection are needed. Without improvement in oral vaccine performance, alternative delivery modalities and schedules may be considered to improve vaccine performance in high transmission settings. |
| Databáze: | OpenAIRE |
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