Safety and Immunogenicity of a 2-Dose Heterologous Vaccine Regimen With Ad26.ZEBOV and MVA-BN-Filo Ebola Vaccines: 12-Month Data From a Phase 1 Randomized Clinical Trial in Nairobi, Kenya

Abstract

Background During the 2014 West African Ebola outbreak, Ebola vaccine development was accelerated. The phase 1 VAC52150EBL1003 study was performed to investigate 2-dose heterologous vaccination with Ad26.ZEBOV and MVA-BN-Filo in an African population located in a high-altitude setting in Nairobi, Kenya. Methods Healthy adult volunteers were randomized to receive one of four 2-dose vaccination schedules. The first vaccination was administered at baseline (Ad26.ZEBOV or MVA-BN-Filo), followed by the second vaccination with the alternate vaccine after either 28 or 56 days. Each schedule had a placebo comparator group. The primary objective was to assess the safety and tolerability of these regimens. Results Seventy-two volunteers were randomized into 4 groups of 18 (15 received vaccine, and 3 received placebo). The most frequent solicited systemic adverse event was headache (frequency, 50%, 61%, and 42% per dose for MVA-BN-Filo, Ad26.ZEBOV, and placebo, respectively). The most frequent solicited local AE was injection site pain (frequency, 78%, 63%, and 33% per dose for MVA-BN-Filo, Ad26.ZEBOV, and placebo, respectively). No differences in adverse events were observed among the different vaccine regimens. High levels of binding and neutralizing anti–Ebola virus glycoprotein antibodies were induced by all regimens and sustained to day 360 after the first dose. Conclusions Two-dose heterologous vaccination with Ad26.ZEBOV and MVA-BN-Filo was well tolerated and highly immunogenic against Ebola virus glycoprotein. Clinical trials registration NCT02376426

Ad26-vector based COVID-19 vaccine encoding a prefusion stabilized SARS-CoV-2 Spike immunogen induces potent humoral and cellular immune responses

“…These findings, however, could not be substantiated in humans as no SARS-CoV vaccine was tested for efficacy. Genetic vaccines like Ad26 have been shown to induce a Th1-biased immune response (Anywaine et al, 2019;Baden et al, 2016;Baden et al, 2013;Barouch et al, 2013;Barouch et al, 2018;Liu et al, 2008;Milligan et al, 2016;Mutua et al, 2019;Radosevic et al, 2010;Shukarev et al, 2017;van der Fits et al, 2020;Winslow et al, 2017), and we have shown here that Ad26.S.PP elicited a dominant…”

“…We have previously shown that vaccines based on transgenes that are delivered by recombinant replication-incompetent adenovirus type 26 vectors (Ad26) have an acceptable safety profile in humans and are able to induce neutralizing and binding antibodies, CD4 and CD8 T cell responses and a Th1-biased immune response in animals and humans (Anywaine et al, 2019;Baden et al, 2016;Baden et al, 2013;Barouch et al, 2013;Barouch et al, 2018;Liu et al, 2008;Milligan et al, 2016;Mutua et al, 2019;Radosevic et al, 2010;Shukarev et al, 2017;van der Fits et al, 2020;Winslow et al, 2017). Furthermore, the availability of industrialized and scalable manufacturing processes makes this an attractive platform for vaccine development.…”

Partnership for Research on Ebola VACcination (PREVAC): protocol of a randomized, double-blind, placebo-controlled phase 2 clinical trial evaluating three vaccine strategies against Ebola in healthy volunteers in four West African countries

“…Two other vaccine strategies, the single-dose GlaxoSmithKline (GSK) ChAd3-EBO Z (replication-de cient Chimpanzee adenovirus type 3-derived vector encoding the Ebola virus Zaire [EBO Z] GP) vaccine and the Johnson & Johnson (J&J) 2-dose heterologous vaccination regimen, Ad26.ZEBOV,MVA-FN-Filo, have completed phase 2 testing. The heterologous two-dose Ad.26.ZEBOV,MVA-BN-Filo vaccine regimen has shown an acceptable safety pro le, was well-tolerated and immunogenic in healthy 18-50 year-old adults volunteers from France and England [3] and Africa countries [4,5]. Data on safety, tolerability and immunogenicity from multiple studies supported the submission of European marketing authorization applications for this investigational Ebola two-dose heterologous vaccine regimen, which have been granted accelerated assessment by European Medical Agency.…”

Pre-clinical studies of a recombinant adenoviral mucosal vaccine to prevent SARS-CoV-2 infection

“…Multiple vaccine candidates are in, or are about to begin, clinical testing. Due to known safety and immunogenicity for epidemic pathogens such as Ebola virus, two leading candidate vaccines are based on recombinant adenovirus vectors; University of Oxford's ChAdOx1-nCov and Janssen Pharmaceutical's AdVac platforms [45][46][47][48] . We saw stronger serum IgG and NAb titers in our study compared to a ChAdOx1-nCov in Balb/c mice 4 , however, this might reflect differences in assay components.…”