Evaluation of a pan-filovirus virus-like particle (VLP) vaccine

The National Institute of Allergy and Infectious Diseases awarded Cincinnati Children's Hospital Medical Center $808,811 on September 1, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to evaluate a pan-filovirus virus-like particle vaccine.

The research evaluates a trivalent filovirus VLP vaccine candidate expressing glycoproteins from Ebola virus, Sudan virus, and Marburg virus. Prior studies in non-human primate models demonstrated that bivalent VLPs expressing Ebola and Sudan virus glycoproteins elicited cross-reactive humoral and cellular immune responses against all pathogenic ebolaviruses (Ebola, Sudan, Bundibugyo, and Tai Forest viruses) and achieved 100 percent protection against lethal mouse-adapted Ebola challenge. The current work extends this approach to trivalent formulations incorporating Marburg virus glycoprotein and assesses their immunogenicity and protective efficacy against the broader filovirus family, which has caused over fifty outbreaks in Africa since 1967 resulting in thousands of deaths.

Cincinnati Children's Hospital Medical Center, a tax-exempt nonprofit pediatric research center based in Cincinnati, Ohio, serves as the recipient. The award covers the period September 1, 2026, through August 31, 2027, with work performed in Cincinnati, Ohio. This is a Project Grant, a standard assistance mechanism under NIAID's infectious disease research program supporting biomedical research and research training at public and nonprofit institutions.

Abstract

Since first discovered in 1967, members of the filoviridae family (ebolaviruses and marburgviruses) have caused >50 outbreaks in many resource-poor countries of africa, resulting in thousands of deaths and often devastating their public health systems and economies. Recently approved ebola vaccines (single shot rvsv-zebov and prime/boost AD26-zebov and MVA-BN-filo), and therapeutic monoclonal antibodies are significant additions to our filovirus outbreak response toolkits. Though quite effective, these vaccines are reported to protect only against the zaire ebola virus (ebov), one of the many pathogenic filoviruses known to cause disease in humans. Their efficacy to protect people against sudan virus (sudv), bundibugyo virus (bdbv), TAÏ forest virus (tafv) and marburg virus (marv) has not been reported yet. Published data from non-human primate (NHP) models of ebola disease (ebod) have shown that animals immunized with ebov glycoprotein (GP)-based vaccines were protected against subsequent challenge with ebov, bdbv or tafv, but not with sudv or marv, suggesting that inclusion of GPS from ebov, sudv and marv in a single vaccine will be sufficient to afford protection against all the pathogenic filoviruses. In our preliminary studies in nhps with bivalent ebola virus-like particles (vlps) expressing GPS from ebov and sudv, we found that the bivalent vlps were highly immunogenic, elicited strong and durable anti-GP humoral and cellular immune responses that cross-reacted with GPS from all pathogenic ebolaviruses (ebov, sudv, bdbv and tafv). In a mouse model of ebola virus disease (EVD), bivalent ebola vlps induced 100% protection against a subsequent challenge with a lethal dose of mouse-adapted (MA)-ebov. We have now added marv GP to the bivalent vlps, thus converting them into trivalent filo-vlps. In our current proposal we propose to evaluate the trivalent filo-vlps for their pan-filovirus vaccine potential. We hypothesize that trivalent filo-vlps elicit strong, broad, and durable pan-filovirus protective immunity. We propose to test this hypothesis across different preclinical models (ferrets, hamsters, nhps and mice) of ebod and marburg disease (mard). We will analyze early innate transcriptomic signature, innate, and adaptive immune responses after immunization with trivalent filo-vlps and identify early transcriptomic signatures that can predict late antibody and/or cellular immune responses that correlate with protection, breadth and/or durability of anti-filovirus protective immunity. Such high value preclinical data is absolutely needed for advancing this highly promising pan-filovirus vaccine candidate into clinical trials.