Determinants of Responses to Oral Vaccines in Developing Countries

Abstract

Oral vaccines which are intended for global use do not necessarily induce the same immune responses in all children worldwide. In fact, several vaccines often induce less frequent and lower mean antibody responses in children in developing countries, suggesting that the vaccines may be less protective among children in these areas. Though the reasons for this less vigorous response are not completely understood, it appears that nutrition-related factors, including both protein-calorie and micronutrient malnutrition, are important aspects in understanding the hyporesponsiveness seen in these children. Related issues including breastfeeding, interference from maternal placental antibodies, intestinal parasitic infections, intestinal mucosal damage and possibly maternal malnutrition during pregnancy also appear to be important. Vaccines designed for oral administration will need to be adjusted to these potential problems in order to maximize benefits for all children. Oral vaccines, when given to children in developing countries, may require higher doses of vaccine, booster doses, calorie, micronutrient and vitamin supplements, withdrawal of breast milk before vaccine administration, deworming medications or other measures to realize their full benefit.

Safety and immunogenicity of an improved oral inactivated multivalent enterotoxigenic Escherichia coli (ETEC) vaccine administered alone and together with dmLT adjuvant in a double-blind, randomized, placebo-controlled Phase I study

“…Of particular interest would be to assess the adjuvant effect in malnourished children in developing countries who are known to respond less well to oral vaccines [22]. Furthermore, previous studies with the first-generation ETEC vaccine have suggested that lower doses of vaccine might be needed to improve tolerability in younger age groups [8].…”

Evaluating the health impact of a public-private partnership

“…6,7 This was of particular importance in view of the fact that other oral vaccines had been found to be less efficacious in developing world settings. 8 Recognizing that the vaccine donation would cover only the first three years of the program, the partners also worked closely to address the long-term sustainability of the vaccine program.…”

Delivery strategies to enhance oral vaccination against enteric infections

“…Therefore, it is generally necessary to incorporate a mucosal adjuvant into the vaccine formulation in order to overcome these challenges, although none have been licensed for oral vaccines to date [36]. A consistent trend has been observed where candidate oral vaccines often perform less effectively in subjects during field trials in endemic areas of developing countries when compared to subjects from developed nations [39]. This phenomenon is known as the "Tropical Barrier" and may have several underlying causes [19].…”