Exploring the Relationship Between Environmental Enteric Dysfunction and Oral Vaccine Responses

Abstract

Oral vaccines significantly underperform in low-income countries. One possible contributory factor is environmental enteric dysfunction (EED), a subclinical disorder of small intestinal structure and function among children living in poverty. Here, we review studies describing oral vaccine responses and EED. We identified eight studies evaluating EED and oral vaccine responses. There was substantial heterogeneity in study design and few consistent trends emerged. Four studies reported a negative association between EED and oral vaccine responses; two showed no significant association; and two described a positive correlation. Current evidence is therefore insufficient to determine whether EED contributes to oral vaccine underperformance. We identify roadblocks in the field and future research needs, including carefully designed studies those can investigate this hypothesis further.

Nutritional status, environmental enteric dysfunction, and prevalence of rotavirus diarrhoea among children in Zambia

“…Evidence suggestive of EED as an explanatory factor for poor oral vaccine performance in developing countries are cohesive with the findings of this analysis [15]. We contribute to evidence suggesting that the same mechanisms that may prevent live attenuated viruses in oral vaccines from replicating in the guts of children with EED may also protect them from wild rotavirus infection [8].…”

“…The synergism between malnutrition and EED yields a cyclical relationship in which malnourished children are more likely to develop EED and in turn remain malnourished due to inadequate absorption of nutrients in the gut and protein wasting [6,11]. The high prevalence of malnutrition and EED in developing countries such as Zambia is also hypothesized to play a role in poor oral rotavirus vaccine performance in low and middle-income countries (LMICs) compared to higher income countries [15,16].…”

Intussusception after Rotavirus Vaccine Introduction in India

“…The safety findings for two different rotavirus vaccines in Africa and India (the present study) are interesting in the context of reduced vaccine performance in these geographic settings. The immunogenicity and efficacy of oral vaccines, including rotavirus vaccines, are lower in low-resource communities 30 , 31 . Factors such as inhibition by higher maternal antibodies in serum or breast milk or co-administration of oral polio vaccine that lower the effective titers of vaccine virus, thus reducing vaccine virus replication and hence immunogenicity, might also lower the risk of intussusception.…”

Immune predictors of oral poliovirus vaccine immunogenicity among infants in South India

“…This phenomenon has prolonged polio eradication by limiting vaccine effectiveness 18 , and is limiting the benefits from the global scale-up in access to oral rotavirus vaccines 19 . However, recent studies of biomarkers of EE in children at the time of immunization have had mixed findings, with different biomarkers showing positive, negative or no association with oral poliovirus or rotavirus vaccine immunogenicity 20 . Several other mechanisms may also contribute to poor oral vaccine immunogenicity in LMICs, including interference by high titers of antigen-specific transplacental or breastmilk antibodies.…”