Homologous and Heterologous Vaccination Regimens With mRNA and rVSV Platforms Induce Potent Immune Responses Against SFTSV Glycoprotein

Authors

Tomaz B. Manzoni, University of PennsylvaniaFollow
Jonna B. Westover, Utah State UniversityFollow
Kendall A. Lundgreen, University of PennsylvaniaFollow
Philip D. Hicks, University of PennsylvaniaFollow
Raegan J. Petch, University of PennsylvaniaFollow
Jordan T. Ort, University of PennsylvaniaFollow
Drew Weissman, University of PennsylvaniaFollow
Steven H. Y. Fan, Acuitas TherapeuticsFollow
Scott E. Hensley, University of PennsylvaniaFollow
Norbert Pardi, University of PennsylvaniaFollow
Brian B. Gowen, Utah State UniversityFollow
Paul Bates, University of PennsylvaniaFollow

Document Type

Article

Author ORCID Identifier

Tomaz B. Manzoni https://orcid.org/0000-0001-6380-5103

Jonna B. Westover https://orcid.org/0000-0002-3642-2980

Philip D. Hicks https://orcid.org/0000-0002-1574-5692

Raegan J. Petch https://orcid.org/0000-0002-4508-4362

Norbert Pardi https://orcid.org/0000-0003-1008-6242

Brian B. Gowen https://orcid.org/0000-0001-9113-2575

Paul Bates https://orcid.org/0000-0002-3918-5976

Journal/Book Title/Conference

Viruses

Volume

17

Issue

8

Publisher

MDPI AG

Publication Date

8-8-2025

Journal Article Version

Version of Record

First Page

1

Last Page

28

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

Abstract

Background: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a highly pathogenic bunyavirus with a high case-fatality ratio for which there is no approved vaccine. Studies have assessed different vaccine technologies. However, few studies have yet assessed the immunogenicity of heterologous prime-boost regimens. Methods: Here, we compare a lipid nanoparticle (LNP)-encapsulated nucleoside-modified mRNA-based vaccine encoding the SFTSV glycoproteins, Gn and Gc, to our recently described recombinant VSV SFTSV (rVSV-SFTSV) vaccine in single dose, homologous, and heterologous prime-boost regimens in mice. Results: We show that all regimens protect from pathogenic SFTSV challenge and elicit strong long-lasting antibody responses. Furthermore, strong cellular immunity is elicited by mRNA-LNP immunizations and by heterologous immunization with an rVSV-SFTSV prime and mRNA-LNP boost. Cellular responses robustly polarized towards a type 1 response, characterized by high levels of IFNγ, TNFα, and IL-2. Immunization with mRNA led to a mixed type 1/type 2 immune response, as determined by antibody isotypes IgG1 and IgG2c. We found that homologous immunization leads to stronger antibody responses while heterologous immunization drives a slightly stronger cellular response. Conclusions: Taken together, the vaccine platforms described here represent strong vaccine candidates for further development.

Recommended Citation

Manzoni, T.B.; Westover, J.B.; Lundgreen, K.A.; Hicks, P.D.; Petch, R.J.; Ort, J.T.; Weissman, D.; Fan, S.H.Y.; Hensley, S.E.; Pardi, N.; et al. Homologous and Heterologous Vaccination Regimens with mRNA and rVSV Platforms Induce Potent Immune Responses Against SFTSV Glycoprotein. Viruses 2025, 17, 1095. https://doi.org/10.3390/v17081095