Geographic disparities impacting oral vaccine performance: Observations and future directions

Abstract

Oral vaccines have several advantages compared with parenteral administration: they can be relatively cheap to produce in high quantities, easier to administer, and induce intestinal mucosal immunity that can protect against infection. These characteristics have led to successful use of oral vaccines against rotavirus, polio, and cholera. Unfortunately, oral vaccines for all three diseases have demonstrated lower performance in the highest-burden settings where they are most needed. Rotavirus vaccines are estimated to have >85% effectiveness against hospitalization in children <12 months in countries with low child mortality, but only ~65% effectiveness in countries with high child mortality. Similarly, oral polio vaccines have lower immunogenicity in developing country settings compared with high-resource settings. Data are more limited for oral cholera vaccines, but suggest lower titers among children compared with adults, and, for some vaccines, lower efficacy in endemic settings compared with non-endemic settings. These disparities are likely multifactorial, and available evidence suggests a role for maternal factors (e.g. transplacental antibodies, breastmilk), host factors (e.g. genetic polymorphisms-with the best evidence for rotavirus-or previous infection), and environmental factors (e.g. gut microbiome, co-infections). Overall, these data highlight the rather ambiguous and often contradictory nature of evidence on factors affecting oral vaccine response, cautioning against broad extrapolation of outcomes based on one population or one vaccine type. Meaningful impact on performance of oral vaccines will likely only be possible with a suite of interventions, given the complex and multifactorial nature of the problem, and the degree to which contributing factors are intertwined.

Keywords: attenuated vaccines; cholera; live; oral vaccines; polio; rotavirus.

Figure 1:

Rotavirus vaccine complete-series coverage (A) and Polio vaccine 3-dose coverage (B) among children by 1 year of age, 2023

Figure 2:

Seroconversion rates in children administered tOPV (from Patriarca et al., [50], Table 1), bOPV (from Macklin et al., [186], Table S1), or mOPV1, 2, 3 (Caceres et al., [53], Table 3) plotted by UNICEF estimated under-five mortality in country and year of study (year of publication used if year of study not reported). Seroconversion adjusted to single dose conversion as 1-(1-S/N)^(1/D), where S is the number seroconverting, N is the number studied, and D is the number of doses administered.

Figure 3.

Seroconversion rates in children administered (from Patriarca et al., [50], Table 1), bOPV (from Macklin et al., [186], Table S1), or mOPV1, 2, 3 (Caceres et al., [53], Table 3) plotted by non-temperate (between Tropic of Cancer and Capricorn) or temperate latitude. Seroconversion adjusted to single dose conversion as 1-(1-S/N)^(1/D), where S is the number seroconverting, N is the number studied, and D is the number of doses administered.