Oral Cholera Vaccine(EuBiologics)

Millions of Euvichol-Plus doses have been deployed from the global oral cholera vaccine stockpile in over 20 cholera-affected countries. However, information on Euvichol-Plus’s effectiveness is limited. Using this vaccine in a cholera epidemic in Dhaka, Bangladesh, provided the opportunity to evaluate the vaccine effectiveness (VE) using a test-negative design.

A two-dose regimen of Euvichol-Plus was administered to individuals aged >1 year in a population of ca. 900 000 in two campaign rounds between June and August 2022, with prospective registration of all persons who received at least one dose. We conducted systematic surveillance in two key facilities, enrolling patients with acute watery diarrhoea who were eligible for vaccination from the campaign’s start and who presented for care between 21 August 2022 and 20 August 2023. Faecal culture-positive cholera cases were matched to up to four faecal culture-negative controls by age, presentation date and facility. Vaccination status was documented without knowledge of culture results. Conditional logistic regression models estimated the OR for the vaccination-cholera association, and the VE of the two-dose regimen was calculated as [(1−OR) × 100].

The analysis included 226 cases and 552 matched controls. The adjusted VE of two doses of the Euvichol-Plus vaccine against medically attended cholera was 66% (99.5% CI: 30 to 83) for all recipients. Limited protection (12%; 95% CI: −95 to 60) was observed for children aged 1–4 years; whereas, protection was 79% (95% CI: 60 to 89) for those aged ≥5 years. VE against cholera with moderate to severe dehydration was 69% (95% CI: 44 to 83) overall but 6% (95% CI: −206 to 71) for children aged 1–4 years.

Euvichol-Plus provided significant protection against medically attended cholera of any severity as well as cholera with moderate to severe dehydration. However, significant levels of protection were only observed for those aged ≥5 years.

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.