A double-blind, placebo-controlled, age-descending, dose-finding trial was undertaken in 40 adults, 60 children aged 10-23 months and 146 aged 6-9 months old (; PACTR201905764389804). Adults received a single full dose of ETVAX and children received 3 doses of either 1/4 or 1/8 of the vaccine. All vaccine doses also included 2.5 ug of dmLT. There were no differences in the frequency of solicited or unsolicited adverse events between vaccine recipients receiving 1/4 and 1/8 dose and no increase in frequency or severity of systemic reactogenicity with increasing number of vaccinations or decreasing age. The vaccine induced plasma IgA and IgG responses against LTB in 100% of the adults and 80-90% of the children. In children aged 6-9 months, IgA response rates against >= 4 vaccine antigens after 3 doses determined as >= 2-fold and >= 4-fold rises were significantly higher for 1/4 dose compared to placebo (65.1% vs 27.6%, p=0.004 and 32.6% vs 6.9%, p=0.01, respectively).
The Zambian studies further demonstrated that ETVAX was safe, tolerable, and immunogenic in adults and children. Using 3 doses, the maximum expected number of doses to be used in children in LMICs, the 1/4 dose was again shown to be safe and induced significant IgA responses in children.
Evaluation of pre-and post-vaccination plasma samples from 20 children aged 10-23 months was accomplished using a proteome microarray. Post-vaccination, reactivity to CFA/1, CS3, CS6, and LTB was stronger than baseline among the vaccinated compared to the placebo group. The CS5 protein was not included in the microarray. Three other purified non-vaccine ETEC proteins; CS4, CS14, and PCF071 had significantly higher post-vaccination responses. These data suggest that ETVAX induces cross-reactive IgG antibody responses to non-vaccine CFs CS4, CS14, and PCF071 from the class 5 fimbriae. This activity could provide some broad IgG antibody coverage beyond the core vaccine antigens (CFA/I, CS3,CS5, CS6 and LTB) themselves.
Field evidence that effective immunization with ETVAX can be protective in man.