Comparison of the immunogenicity and protective efficacy of ACAM2000, MVA, and vectored subunit vaccines for Mpox in rhesus macaques.

The 2022-2023 mpox outbreak triggered vaccination efforts using smallpox vaccines that were approved for mpox, including modified vaccinia Ankara (MVA; JYNNEOS), which is a safer alternative to live replicating vaccinia virus (ACAM2000). Here, we compare the immunogenicity and protective efficacy of JYNNEOS by the subcutaneous or intradermal routes, ACAM2000 by the percutaneous route, and subunit Ad35 vector-based L1R/B5R or L1R/B5R/A27L/A33R vaccines by the intramuscular route in rhesus macaques. All vaccines provided robust protection against high-dose intravenous mpox virus challenge with the current outbreak strain, with ACAM2000 providing near complete protection and JYNNEOS and Ad35 vaccines providing robust but incomplete protection. Protection correlated with neutralizing antibody responses as well as L1R/M1R- and B5R/B6R-specific binding antibody responses, although additional immune responses likely also contributed to protection. This study demonstrates the protective efficacy of multiple vaccine platforms against mpox virus challenge, including both current clinical vaccines and vectored subunit vaccines.

Single-vial filovirus glycoprotein vaccines: Biophysical characteristics and immunogenicity after co-lyophilization with adjuvant.

Zaire ebolavirus (EBOV), Sudan ebolavirus (SUDV), and Marburg marburgvirus (MARV) are the most prevalent and pathogenic species of filovirus. Previously, we showed that glycoprotein antigens from each virus could be lyophilized to create thermostable monovalent subunit vaccines. However, cross-protection is not expected from the monovalent vaccines and therefore developing a trivalent filovirus vaccine would be desirable. Subunit protein vaccines often require the addition of an adjuvant to sufficiently boost the immunogenicity. Typically, liquid suspensions or emulsions of adjuvants and lyophilized antigens are stored in separate vials to avoid destabilizing interactions and are only mixed immediately before administration. Herein, we describe the development and characterization of monovalent and trivalent filovirus vaccines that are co-lyophilized with a squalane-in-water emulsion adjuvant. We found that the single-vial presentation retained adjuvant particle diameter and zeta potential after lyophilization and reconstitution. Furthermore, the trivalent vaccines elicited high antibody levels against all three antigens in mice and non-human primates. These results advance the prospect of developing a single-vial trivalent filovirus vaccine, which would enable easier distribution and administration of the vaccine to resource-poor areas.