Live-vectored broadly protective ebola virus mucosal vaccine

We have developed an attenuated, replication-competent Bovine Parainfluenza Virus Genotype C vector (BPI3Vc) and used it to generate multiple prototype subunit vaccines that have demonstrated immunogenicity and protective efficacy in animal studies (PMID: 41766820). One of the lead candidates targets Highly Pathogenic Avian Influenza H5N1. In an efficacy study conducted in the last two months, mucosal prime-boost immunization of dairy cows conferred robust protection against intramammary H5N1 challenge, whereas negative controls exhibited milk virus titers as high as 10⁸ within 24 hours of challenge. The same vaccine also induced strong antibody responses in pigs. We are evaluating the H5N1 vaccine in chickens following in ovo immunization. Building on the proven performance of the BPI3Vc platform in the actual hosts that require protection, we are developing a contemporary multivalent Ebola vaccine engineered to express glycoproteins (GP) and nucleoproteins (NP) from Bundibugyo, Zaire, and Sudan ebolaviruses. The GP antigens are intended to induce protective neutralizing antibodies, while the NP antigens are designed to elicit cellular immune responses and broaden cross-species protection through their conserved sequences. The BPI3Vc platform offers several key advantages:

1. Multivalent, adaptable antigen design – Surface-displayed GP antigens and cytosolically expressed NP antigens from multiple Ebolavirus species are delivered using a modular, scalable platform that supports rapid incorporation of additional strains. This approach preserves native antigen conformation and critical epitopes, facilitating development of broadly protective vaccines that can be rapidly updated to address emerging variants.
2. Broad protection – A single vaccine formulation designed to elicit protective immunity against all clinically relevant Ebolavirus species, including Bundibugyo, Zaire, and Sudan viruses.
3. Mucosal and systemic immunity – Intranasal administration targets the primary portal of infection, inducing local and systemic immune responses that may prevent infection and transmission. The vaccine can also be administered intramuscularly or subcutaneously to maximize systemic immunity.
4. Scalability and ease of deployment – As a live-vectored vaccine, the platform is readily scalable, straightforward to manufacture using already approved cell lines and purify, and amenable to rapid deployment during outbreaks. The platform has demonstrated stable antigen expression through at least ten serial passages and protective efficacy against diverse pathogens in animal studies. Collectively, this approach offers a flexible, rapidly deployable vaccine platform capable of supporting strain-matched Ebola control, broadening cross-species protection, and strengthening regional and global outbreak preparedness.