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

Abstract

Background Ebola vaccine development was accelerated in response to the 2014 Ebola virus infection outbreak. This phase 1 study (VAC52150EBL1004) assessed safety, tolerability, and immunogenicity of heterologous 2-dose Ad26.ZEBOV, MVA-BN-Filo vaccination regimens in the Lake Victoria Basin of Tanzania and Uganda in mid-level altitude, malaria-endemic settings. Methods Healthy volunteers aged 18–50 years from Tanzania (n = 25) and Uganda (n = 47) were randomized to receive placebo or active vaccination with Ad26.ZEBOV or MVA-BN-Filo (first vaccination), followed by MVA-BN-Filo or Ad26.ZEBOV (second vaccination) dose 2, respectively, with intervals of 28 or 56 days. Results Seventy-two adults were randomized to receive vaccine (n = 60) or placebo (n = 12). No vaccine-related serious adverse events were reported. The most frequent solicited local and systemic adverse events were injection site pain (frequency, 70%, 66%, and 42% per dose for MVA-BN-Filo, Ad26.ZEBOV, and placebo, respectively) and headache (57%, 56%, and 46%, respectively). Adverse event patterns were similar among regimens. Twenty-one days after dose 2, 100% of volunteers demonstrated binding antibody responses against Ebola virus glycoprotein, and 87%–100% demonstrated neutralizing antibody responses. Ad26.ZEBOV dose 1 vaccination induced more-robust initial binding antibody and cellular responses than MVA-BN-Filo dose 1 vaccination. Conclusions Heterologous 2-dose vaccination with Ad26.ZEBOV and MVA-BN-Filo against Ebola virus is well tolerated and immunogenic in healthy volunteers. Clinical trials registration NCT02376400.

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.…”

Elicitation of potent neutralizing antibody responses by designed protein nanoparticle vaccines for SARS-CoV-2

“…For example, existing nucleic acid and vectored vaccine platforms enabled rapid entry into the clinic with vaccines encoding SARS-CoV-2 S antigens (Folegatti et al, 2020;Jackson et al, 2020;Mulligan et al, 2020;Sahin et al, 2020;Yu et al, 2020;Zhu et al, 2020a). However, the safety, efficacy, and scalability of these vaccine modalities are not fully understood, as there are currently no DNA or mRNA vaccines licensed for human use, and the first viral vector vaccine was approved only within the last few months (Anywaine et al, 2019). In contrast, self-assembling or particulate protein immunogens are a clinically validated vaccine modality with a proven track record of safety and efficacy in humans (Lopez-Sagaseta et al, 2016).…”

A Pentavalent Epstein-Barr Virus-Like Particle Vaccine Elicits High Titers of Neutralizing Antibodies against Epstein-Barr Virus Infection in Immunized Rabbits

“…Thus, in its current state, our system is hindered by low productivity relative to the number of cells needed to produce a small working VLP stock for animal experiments, with no potential for scalability. To boost overall immunogenicity, establish efficient and robust expression of all glycoproteins, and improve efficiency and scalability of the EBV-LP production process, future studies will explore the use of live-attenuated vectors, such as modified vaccinia Ankara (MVA), chimpanzee adenovirus 3, and/or vesicular stomatitis virus to deliver EBV-LPs and EBV antigens, as was done recently for Ebola virus with very promising results in pre-clinical and Phase Ib clinical trials [66][67][68][69][70][71][72][73]. In the field of EBV vaccinology, viral vaccine vectors, particularly adenoviral and MVA vectors, have been used both pre-clinically and clinically in the context of therapeutic and prophylactic vaccination.…”