Safety, reactogenicity, and immunogenicity of a chimpanzee adenovirus vectored Ebola vaccine in adults in Africa: a randomised, observer-blind, placebo-controlled, phase 2 trial

Abstract

Background: The 2014 Zaire Ebola virus disease epidemic accelerated vaccine development for the virus. We aimed to assess the safety, reactogenicity, and immunogenicity of one dose of monovalent, recombinant, chimpanzee adenovirus type-3 vectored Zaire Ebola glycoprotein vaccine (ChAd3-EBO-Z) in adults. Methods This phase 2, randomised, observer-blind, controlled trial was done in study centres in Cameroon, Mali, Nigeria, and Senegal. Healthy adults (≥18 years) were randomly assigned with a web-based system (1:1; minimisation procedure accounting for age, gender, centre) to receive ChAd3-EBO-Z (day 0), or saline placebo (day 0) and ChAd3-EBO-Z (month 6). The study was observer-blind until planned interim day 30 analysis, single-blind until month 6, and open-label after month 6 vaccination. Primary outcomes assessed in the total vaccinated cohort, which comprised all participants with at least one study dose administration documented, were serious adverse events (up to study end, month 12); and for a subcohort were solicited local or general adverse events (7 days postvaccination), unsolicited adverse events (30 days post-vaccination), haematological or biochemical abnormalities, and clinical symptoms of thrombocytopenia (day 0-6). Secondary endpoints (subcohort; per-protocol cohort) evaluated anti-glycoprotein Ebola virus antibody titres (ELISA) pre-vaccination and 30 days post-vaccination. This study is registered with ClinicalTrials.gov, NCT02485301.

Innate Immune Responses to Chimpanzee Adenovirus Vector 155 Vaccination in Mice and Monkeys

“…Owing to their lower seroprevalence and thus decreased vector neutralization in humans as compared to human Ad5, chimpanzee Ad (ChAd) vectors represent an attractive vaccine platform (3)(4)(5). ChAdvectored candidate vaccines against infectious diseases such as malaria, Ebola, and RSV have shown favorable immunogenicity and tolerability in humans (6)(7)(8)(9)(10)(11). These vaccines drive robust intracellular antigen expression, thus promoting a CD8 + T-cellbiased response, but were also shown to induce antigen-specific CD4 + T-cell responses and antibodies.…”

Single-dose immunization with a chimpanzee adenovirus-based vaccine induces sustained and protective immunity against SARS-CoV-2 infection

“…Furthermore, the same adenovirus vector expressing the full-length S protein of MERS-CoV was also evaluated in a phase I human trial and demonstrated good safety and tolerability 4 . ChAd3 vectors expressing Ebola Zaire glycoprotein (ChAd3-EBO-Z) elicited strong immune responses in clinical trial participants 34,35 . These results highlight the favorable safety, tolerability, and immunogenicity profiles of chimpanzee adenovirus vector-based vaccines in humans, which hold great promise for vaccine development.…”

“…This is in great contrast to the immunity induced by other candidate vaccines, for which immunogenicity is short-lived and multiple rounds of immunization are required to induce detectable levels of neutralizing antibodies or to confer protection against viral challenge 1,30 . Furthermore, recombinant vaccines based on AdC68 and other rare serotype chimpanzee adenoviral vectors, such as ChAd63 and ChAd3, have recently been engineered to express various antigens, with some demonstrating impressive safety and immunogenicity profiles in clinical studies [31][32][33][34][35] . These unique features and our prior experience in handling the chimpanzee adenovirus vectors provided a critical foundation and rationale for the development of a SARS-CoV-2 vaccine based on ChAdTS.…”

COVID-19 Vaccines and Thrombosis—Roadblock or Dead-End Street?

“…In the case of Ad-based vaccine applications, two phase II clinical trials have been conducted for Ebola virus vaccines [26,27]. The simian ChAdOx1 vector expressing the Ebola virus glycoprotein (ChAd3-EBO-Z) was administered to 1509 adults, and although injection site pain and serious non-vaccine related events were recorded, no clinically meaningful thrombocytopenia was registered [26]. In the other phase II trial, the ChAd3-EBO-Z vaccine was administered to 300 healthy children, six years old or younger [27].…”