MVA-based vaccines are protective against lethal eastern equine encephalitis virus aerosol challenge in cynomolgus macaques

Brandon J Beddingfield; Kenneth S Plante; Jessica A Plante; Scott C Weaver; Sarah Bose; Clara Krzykwa; Nicole Chirichella; Rachel K Redmann; Stephanie Z Seiler; Jason Dufour; Robert V Blair; Kathrin Endt; Ariane Volkmann; Nicholas J Maness; Chad J Roy

doi:10.1038/s41541-024-00842-y

MVA-based vaccines are protective against lethal eastern equine encephalitis virus aerosol challenge in cynomolgus macaques

NPJ Vaccines. 2024 Feb 27;9(1):47. doi: 10.1038/s41541-024-00842-y.

Authors

Brandon J Beddingfield¹, Kenneth S Plante^{2

3}, Jessica A Plante^{2

3}, Scott C Weaver^{2

3}, Sarah Bose¹, Clara Krzykwa¹, Nicole Chirichella¹, Rachel K Redmann¹, Stephanie Z Seiler¹, Jason Dufour⁴, Robert V Blair⁵, Kathrin Endt⁶, Ariane Volkmann⁶, Nicholas J Maness^{1

7}, Chad J Roy^{8

9}

Affiliations

¹ Division of Microbiology, Tulane National Primate Research Center, Covington, LA, USA.
² Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.
³ World Reference Center for Emerging Viruses and Arboviruses, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.
⁴ Division of Veterinary Medicine, Tulane National Primate Research Center, Covington, LA, USA.
⁵ Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA, USA.
⁶ Bavarian Nordic GmbH, Fraunhofer Strasse 13, 82152, Martinsried, Germany.
⁷ Department of Microbiology and Immunology, Tulane School of Medicine, New Orleans, LA, USA.
⁸ Division of Microbiology, Tulane National Primate Research Center, Covington, LA, USA. croy@tulane.edu.
⁹ Department of Microbiology and Immunology, Tulane School of Medicine, New Orleans, LA, USA. croy@tulane.edu.

Abstract

MVA-based monovalent eastern equine encephalitis virus (MVA-BN-EEEV) and multivalent western, eastern, and Venezuelan equine encephalitis virus (MVA-BN-WEV) vaccines were evaluated in the cynomolgus macaque aerosol model of EEEV infection. Macaques vaccinated with two doses of 5 × 10⁸ infectious units of the MVA-BN-EEEV or MVA-BN-WEV vaccine by the intramuscular route rapidly developed robust levels of neutralizing antibodies to EEEV that persisted at high levels until challenge at day 84 via small particle aerosol delivery with a target inhaled dose of 10⁷ PFU of EEEV FL93-939. Robust protection was observed, with 7/8 animals receiving MVA-BN-EEEV and 100% (8/8) animals receiving MVA-BN-WEV surviving while only 2/8 mock vaccinated controls survived lethal challenge. Complete protection from viremia was afforded by both vaccines, with near complete protection from vRNA loads in tissues and any pathologic evidence of central nervous system damage. Overall, the results indicate both vaccines are effective in eliciting an immune response that is consistent with protection from aerosolized EEEV-induced disease.

Grants and funding

HHSN272201700011C/AI/NIAID NIH HHS/United States