Use of an ETEC proteome microarray to evaluate cross-reactivity of ETVAX® vaccine-induced IgG antibodies in Zambian children

Enterotoxigenic E. coli (ETEC) is a major cause of moderate to severe diarrhoea in low-middle income countries (LMICs) and affects mostly children and travelers to endemic regions. ETEC are highly diverse pathovar with over 25 colonisation factors (fimbriae) described. The development of a broadly protective vaccine to cover most of the ETEC variants is critical for disease control. This study evaluated whether vaccination with ETVAX®; the most clinically advanced ETEC vaccine candidate results in IgG responses that cross-react with other ETEC antigens/ colonisation factors not overexpressed in the vaccine. A proteome microarray was used to assess IgG responses before and after vaccination to gain insight in the antigenic composition of ETEC that children in Zambia are exposed to and to see whether ETVAX® provides a level of cross-protection against antigens not expressed in the vaccine. The study shows that ETVAX® containing CFA/1, elicits antibodies that cross-react with other class 5 fimbriae and has the potential to offer broad protection. We also see that other antigens apart from classical antigens are immunodominant and possibly play a role in ETEC pathogenesis and may need to be investigated for their role in protection 40 samples were evaluated from 20 participants of a single-site, double-blind, placebo-controlled, age-descending phase 1 trial investigating the safety, tolerability, and immunogenicity of an oral inactivated ETEC Vaccine (ETVAX®) adjuvanted with dmLT. 4 children were from the placebo group, received a 1/4 dose and 8 received a 1/8 dose of the adult vaccine dose. Blood samples were collected at baseline (pre-vaccination or D0 or visit 1 (V1)) and seven days after the third dose (D97 or visit 7 (V7)). We analysed 20 V1 samples and 20 V7 samples.