Recombinant vesicular stomatitis viruses (rVSVs) engineered to express heterologous viral glycoproteins have proven to be remarkably effective vaccines. Indeed, rVSV-EBOV, which expresses the Ebola virus (EBOV) glycoprotein, recently received clinical approval in the United States and Europe for its ability to prevent EBOV disease. Analogous rVSV vaccines expressing glycoproteins of different human-pathogenic filoviruses have also demonstrated efficacy in pre-clinical evaluations, yet these vaccines have not progressed far beyond research laboratories. In the wake of the most recent outbreak of Sudan virus (SUDV) in Uganda, the need for proven countermeasures was made even more acute. Here we demonstrate that an rVSV-based vaccine expressing the SUDV glycoprotein (rVSV-SUDV) generates a potent humoral immune response that protects guinea pigs from SUDV disease and death. Although the cross-protection generated by rVSV vaccines for different filoviruses is thought to be limited, we wondered whether rVSV-EBOV might also provide protection against SUDV, which is closely related to EBOV. Surprisingly, nearly 60% of guinea pigs that were vaccinated with rVSV-EBOV and challenged with SUDV survived, suggesting that rVSV-EBOV offers limited protection against SUDV, at least in the guinea pig model. These results were confirmed by a back-challenge experiment in which animals that had been vaccinated with rVSV-EBOV and survived EBOV challenge were inoculated with SUDV and survived. Whether these data are applicable to efficacy in humans is unknown, and they should therefore be interpreted cautiously. Nevertheless, this study confirms the potency of the rVSV-SUDV vaccine and highlights the potential for rVSV-EBOV to elicit a cross-protective immune response.

Marburg virus (MARV) is a negative-sense, single-stranded RNA virus that belongs to the Filoviridae family. Despite having caused numerous outbreaks of severe hemorrhagic fever with high case fatality rates, there are still no clinically approved therapeutics or vaccines to treat or prevent MARV disease. Recombinant vesicular stomatitis viruses (rVSVs) expressing heterologous viral glycoproteins have shown remarkable promise as live-attenuated vaccine vectors, with an rVSV-based Ebola virus vaccine having received regulatory approval in the United States and numerous other countries. Analogous rVSV vaccine vectors have also been developed for MARV and have shown efficacy in several preclinical studies conducted in nonhuman primates. Here, we used a guinea pig model to confirm the protective efficacy of a cloned, rVSV-based candidate vaccine, termed PHV01, expressing the MARV variant Angola glycoprotein. Our results demonstrated that a single dose (2 × 10⁶ PFU) of vaccine administered 28 days prior to challenge with a uniformly lethal dose of guinea-pig-adapted MARV variant Angola provided complete protection from death and disease. Moreover, protection was robust, with as little as 200 PFU of vaccine conferring significant protection. Not only does this study highlight the potential predictive value of the guinea pig model in the evaluation of MARV countermeasures, but it also demonstrates consistent and reproducible protection afforded by a clonal vaccine candidate. Indeed, this study identifies PHV01 as a suitable vaccine candidate for advanced development.

Marburg virus (MARV), a filovirus, was first identified in 1967 in Marburg, Germany, and Belgrade, former Yugoslavia. Since then, MARV has caused sporadic outbreaks of human disease with high case fatality rates in parts of Africa, with the largest outbreak occurring in 2004/05 in Angola. From 2021 to 2023, MARV outbreaks occurred in Guinea, Ghana, New Guinea, and Tanzania, emphasizing the expansion of its endemic area into new geographical regions. There are currently no approved vaccines or therapeutics targeting MARV, but several vaccine candidates have shown promise in preclinical studies. We compared three vaccine platforms simultaneously by vaccinating hamsters with either a single dose of an adenovirus-based (ChAdOx-1 MARV) vaccine, an alphavirus replicon-based RNA (LION-MARV) vaccine, or a recombinant vesicular stomatitis virus-based (VSV-MARV) vaccine, all expressing the MARV glycoprotein as the antigen. Lethal challenge with hamster-adapted MARV 4 weeks after vaccination resulted in uniform protection of the VSV-MARV and LION-MARV groups and 83% of the ChAdOx-1 MARV group. Assessment of the antigen-specific humoral response and its functionality revealed vaccine-platform-dependent differences, particularly in the Fc effector functions.

Filoviruses, like the Marburg (MARV) and Ebola (EBOV) viruses, have caused outbreaks associated with significant hemorrhagic morbidity and high fatality rates. Vaccines offer one of the best countermeasures for fatal infection, but to date only the EBOV vaccine has received FDA licensure. Given the limited cross protection between the EBOV vaccine and Marburg hemorrhagic fever (MHF), we analyzed the protective efficacy of a similar vaccine, rVSV-MARV, in the lethal cynomolgus macaque model. NHPs vaccinated with a single dose (as little as 1.6 × 10⁷ pfu) of rVSV-MARV seroconverted to MARV G-protein prior to challenge on day 42. Vaccinemia was measured in all vaccinated primates, self-resolved by day 14 post vaccination. Importantly, all vaccinated NHPs survived lethal MARV challenge, and showed no significant alterations in key markers of morbid disease, including clinical signs, and certain hematological and clinical chemistry parameters. Further, apart from one primate (from which tissues were not collected and no causal link was established), no pathology associated with Marburg disease was observed in vaccinated animals. Taken together, rVSV-MARV is a safe and efficacious vaccine against MHF in cynomolgus macaques.

Clinical trials conducted in low resource settings of vaccines against unlikely pandemics generate practical barriers to achieving genuine informed consent. Uncertainty over the likelihood of the occurrence of emerging disease threats complicates risk-benefit considerations. We explored how people interpreted the language of a draft consent form for a Phase II trial of a vaccine against Nipah virus (NiV), a lethal bat-borne zoonosis, and assessed their willingness to participate after learning about the trial procedures. We conducted a mixed-methods study collecting data from residents of Dhaka city, and Faridpur District between December 2021 and November 2022. Our qualitative team revised a draft consent form with input from the community, while the quantitative team conducted face-to-face interviews of 978 household heads making vaccine and treatment decisions. We presented the consent form to 20 respondents. They expressed a desire to learn more about NiV disease and sought clarification on the vaccine trial process, use of a placebo, privacy and confidentiality, potential side effects, and compensation procedures. During the quantitative survey, among 328 respondents who indicated a willingness to participate in the vaccine trial, only 1 % (3/328) were familiar with the concept of a placebo. After the quantitative data collection team explained the meaning of a placebo, 61 % (199/328) expressed their willingness to participate in the trial. Our data suggest that obtaining informed consent for vaccine trials against pathogen with pandemic potentials is feasible but requires a commitment to eliciting study participants' perspectives and tailoring study materials to address their concerns and gaps in understanding.

Nipah virus (NiV) is a deadly zoonotic disease with pandemic potential, prioritized by the World Health Organization for research and vaccine development. Since Bangladesh has faced annual NiV outbreaks and repeated spillovers since 2001, it is likely to be the site of a Phase II vaccine trial. This study explored people's knowledge about NiV and their willingness to participate in a NiV vaccine trial in Bangladesh. We conducted a mixed methods study, collecting qualitative and quantitative data from Mirpur township, Dhaka, and NiV-affected Faridpur District. From December 2021 to November 2022, the team interviewed adult male and female respondents responsible for household treatment and vaccination decisions. The team conducted 66 in-depth interviews and 978 survey interviews. Many in-depth interviewees were aware of NiV and, when asked if they would participate in a NiV vaccine trial, responded with one of three options: willing, unwilling, or would decide later. They were concerned about vaccine safety and side effects when making a decision about participation. In the survey, more respondents from Mirpur township, Dhaka, had heard about a disease transmitted from bats to people (57 %, 272/478 vs. 52 %, 262/500) and were willing to participate in a vaccine trial (45 %, 217/478 vs. 22 %, 111/500) than those from Faridpur. A high number expressed willingness to take an investigational NiV vaccine during an outbreak (Dhaka 75 %, 205/272 vs. Faridpur 81 %, 398/491 Faridpur). We did not find any association between knowledge about NiV and willingness to participate in a NiV vaccine trial. Many respondents expressed willingness to participate in a NiV vaccine trial, especially during an outbreak, suggesting that such a trial may be feasible in Bangladesh. Given concerns about safety and side effects, clear communication on these issues may support informed participation.