Mechanistic analysis of a combined liposome-TLR7/8-agonist adjuvanted virus-like particle vaccine

The National Institute of Allergy and Infectious Diseases awarded Oregon Health & Science University $769,147 on August 3, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to conduct mechanistic analysis of adjuvanted virus-like particle vaccines.

The recipient will elucidate the mechanism of action of combined adjuvants in a virus-like particle-based vaccine by testing three lipid-based adjuvant platforms—an AS01-like cationic liposome adjuvant formulation, an MF59-like emulsion adjuvant formulation, and ionizable lipid nanoparticles—each paired with a Powassan virus-like particle antigen. Work includes determining optimal adjuvant pairings based on adaptive immune response elicitation, response durability, and protection from challenge in a mouse model; examining single-cell transcriptional signatures in draining lymph nodes using single-cell RNA sequencing with cellular indexing of transcriptomes and epitopes by sequencing; and extending findings to a non-human primate model to assess immune response generation and lymph node transcriptional signatures post-vaccination.

The award runs through July 31, 2031. Performance occurs in Portland, Oregon. Oregon Health & Science University, a state-controlled academic medical center and research institution, serves as the prime recipient for this project grant award, which is structured as assistance funding rather than a contract.

Abstract

Mechanistic analysis of a combined lipid-TLR7/8-agonist adjuvanted virus-like particle vaccine this proposal is focused on elucidating the mechanism of action of combinations of adjuvants in a virus-like particle (VLP) based vaccine. The adjuvant combinations will consist of a TLR7/8 agonist formulated with one of three lipid-based platforms. These platofrms are: 1) AS01-like cationic liposome adjuvant formulation (LAF); 2) MF59-like emulsion adjuvant formulation (EAF); 3) ionizable lipid nanoparticles (lnps), the combined adjuvants will be paired with a powassan virus (powv)-like particle antigen. We will determine an optimal adjuvant pairing based on elicitation of adaptive immune responses, durability of the response and protection from challenge in a mouse model of virus infection. We will further examine the transcriptional signature of individual cells in the draining lymph nodes of vaccinated animals using single cell RNA sequencing (scrnaseq) with cellular indexing of transcriptomes and epitopes by sequencing (cite-SEQ). Finally, we will extend the results obtained in mice to a non-human primate model, in which we will examine the generation of an immune response as well as lymph node transcriptional signatures post vaccination, allowing comparison of mouse data with an outbred, highly translational model. Powv is a potentially emerging public health threat that is present in much of the northeastern and midwestern united states. Further, we expect that data obtained in this proposal will also be applicable to vaccine design for additional viral pathogens.