Vaccines for the prevention of severe disease caused by Ebola virus and SARS-CoV-2 virus
are routinely offered to adults at higher risk of exposure in African settings. For
protection from Ebola virus, the main target populations are epidemiologically-identified
and include healthcare workers, refugees, and people living in outbreak zones. These
target populations are also routinely offered vaccines for other vaccine-preventable
diseases. However, there are currently no data on whether the co-administration of
rVSVΔG-ZEBOV-GP with other vaccines has an acceptable profile of reactogenicity and
antigen-specific immunogenicity, and concomitant use of rVSVΔG-ZEBOV-GP with other
vaccines is not recommended. Clinical trial data on the co-administration of
rVSVΔG-ZEBOV-GP with other vaccines prioritised for the same population, and especially
in the context of a new era in mRNA vaccine technology, would have significant relevance
to how protection to more than one disease can be provided at a single visit to a
vaccination clinic. This, in turn, has the potential to improve vaccine coverage and
improve the efficiency of vaccine policy and logistics, as well as being the first step
evaluation in the evaluation of Vesicular stomatitis virus-vectored vaccine technology
with lipid-enveloped mRNA platforms that are going to be increasingly used in other
formulations against other/future infectious diseases targets.

There are no preliminary data in this first-of-kind study.

The advent of the SARS-CoV-2 virus and COVID-19 pandemic signalled the accelerated
development of lipid-nanoparticle mRNA vaccine technology with great success. The mRNA
platform is highly adaptable to new disease targets, including cancer and infectious
diseases pathogens, and a multitude of vaccine candidates are currently in development
for outstanding global health priorities that have eluded pre-pandemic technologies.
However, there remains very little known about using mRNA technologies in combination
with, or concurrent to, other vaccine technologies and whether there are any adverse
signals associated with safety or antigen-specific immune response/protection. Earlier
trials have focussed on using SARS-CoV-2 mRNA vaccines in combination with
adjuvant-protein vaccines for seasonal influenza (and herpes-zoster virus, in setup) and
have reported favourable safety and humoral immune responses that has resulted in
recommended concurrent vaccine dose administration into the annual seasonal vaccination
schedule of UK nationals. These study data have significantly supported public confidence
in accepting two licenced vaccines at the same time and significant efficiency gains in
vaccine coverage and public protection. The concurrent administration of mRNA vaccines
with attenuated or replication-incompetent viral-vectored vaccines has not, to our
knowledge, been assessed although many trials reported favourable safety and
immunogenicity with heterologous combinations of these vaccine platforms for protection
against COVID-19. Since existing mRNA COVID-19 vaccines and new mRNA constructs against
other infectious diseases are expected to become routine immunisations for key members of
the population, such as healthcare workers and older adults, research is needed to inform
whether concurrent or co-administration with other vaccines are possible. For African
populations, the risk of disease outbreaks from Ebola remains high and the future use of
rVSVΔG-ZEBOV-GP is expected, along with other measures, to mitigate the risks to
healthcare workers and the wider public. Assessing the safety and immunogenicity of
rVSVΔG-ZEBOV-GP vaccine in the context of expected gains in public confidence and policy
implementation with co-administration with mRNA vaccine technologies is a major subject
of interest for African populations and preparedness for future disease outbreaks.

This is a single-centre, randomized, single-blinded, vaccine safety and immunogenicity
study in healthy adults living in Rwanda. The EbolaCov trial aims to inform whether the
Ebola vaccine rVSVΔG-ZEBOV-GP can be administered concurrent to a BioNTech - Pfizer
COVID-19 booster dose without an unacceptable increase in reactogenicity and/or loss of
humoral immunogenicity to Ebola vaccine antigen.

The investigators aim to primarily recruit participants who are current healthcare
workers, although the study will be open all eligible members of the public. Participants
of both genders aged 18-50 years who are in good health and who are able to provide
written informed consent, will be eligible for inclusion in this study. The recruitment
target is recruit 72 participants who will be randomised in a 1:1 ratio to one of two
groups.

There will be four study visits over 6 months. Participants will be monitored for any
reactions and other adverse events for 7 days after each immunisation via self reported
e-diary, and for significant adverse events throughout the study.

The geometric mean titre (GMT) and antigen-specific antibody titre will be measured by
glycoprotein-enzyme-linked immunosorbent assay at baseline, 28-days and 180-days after
vaccination.