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IgA response poor indicator of rotavirus vaccine protection in infants
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Infants residing within Dhaka, Bangladesh, who received the live oral rotavirus vaccine Rotarix had weak rotavirus immunoglobulin responses, which were significantly impaired by maternal antibodies, according to study results.
Researchers suggested that immunoglobulin A may not be an effective marker of an infant’s protection from rotavirus diarrhea in low-income countries.
“Vaccines are only half as effective in low-income countries, where child mortality is high and disease burden is greatest, compared with high-income countries,” Benjamin Lee, MD, assistant professor in the department of pediatrics at the University of Vermont Larner College of Medicine, and colleagues wrote. “The standard measure of rotavirus vaccine immunogenicity is [serum rotavirus-specific immunoglobulin A (RV-IgA)], which correlates with vaccine efficacy at the population, especially in high-income countries.”
The researchers wrote that it is unclear whether this measure is effective in predicting individual children’s protection against rotavirus diarrhea in low-income countries. This knowledge could enhance vaccine research by removing clinical endpoints, such as rotavirus diarrhea, in clinical trials conducted in the future.
Lee and colleagues analyzed findings from the Performance of Oral Vaccines in Developing Countries (PROVIDE) study, which included 700 infants who randomly received Rotarix (GlaxoSmithKline) or no Rotarix at 10 to 17 weeks of life. Follow-up involved active diarrheal surveillance.
Infants who received Rotarix demonstrated an overall RV-IgA geometric mean concentration of 21 U/mL. Only 27% seroconverted, and 32% demonstrated seropositivity following vaccination, which, according to the researchers, are lower than previously reported frequencies in this area. Increased maternal antibodies that were directly related to rotavirus significantly reduced immunogenicity in infants, they said.
Rotavirus diarrhea risk was reduced in those who seroconverted until they reached 1 year of age; however, seropositivity explained only a small portion of Rotarix’s effect demonstrated by the clinical endpoint of rotavirus diarrhea (7.8%).
“This population demonstrated qualitative and quantitative defects in RV-IgA response: Few children responded, and those who did had relatively weak responses that were often short-lived,” Lee and colleagues wrote. “Bangladesh applied for Gavi approval in 2016, but Rotarix is not yet publicly available. Under current conditions, clinical effectiveness may fail to reach full potential.” – by Katherine Bortz
Disclosures: Lee reports funding from the Bill & Melinda Gates Foundation under awards OPP1017093 and OPP1127782. Please see the study for a list of all other authors’ relevant financial disclosures.
Perspective
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Andi L. Shane, MD, MPH, MSc
This sub-analysis of the PROVIDE birth cohort study illustrates two challenges associated with oral vaccine performance in resource-challenged settings. The first is the well-described decreased rotavirus vaccine effectiveness, likely due to one or more factors, separated into maternal factors (rotavirus-specific serum and human milk antibodies) and host factors such as malnutrition, which may affect oral vaccine uptake.
The second challenge, which is not unique to rotavirus vaccine evaluation, relates to the identification of the correlates of protection. An objective, measurable biological parameter — for example, serum rotavirus IgA — is highly desirable; however, an outcome, such as medically attended encounters, for rotavirus-related disease may have more clinical relevance to the stakeholder.
Studies such as this collaborative effort accentuate the importance of elucidating individual vs. population-based and biological vs. clinical outcomes to optimize the development of immunization schedules by public health organizations.
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