Immunogenicity and Protective Efficacy of Psoralen-Inactivated SARS-CoV-2 Vaccine in Nonhuman Primates

John W. Sanders, Daniel Ewing, Appavu K. Sundaram*, Christopher Scott Gamble, Maria Blevins, Zhaodong Liang, Leigh Ann Sanders, David A. Ornelles, Peifang Sun, Klara Lenart, Hendrik Feuerstein, Karin Loré, Nikolai Petrovsky, Maya Williams, Kevin R. Porter

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has significantly impacted public health and the economy worldwide. Most of the currently licensed COVID-19 vaccines act by inhibiting the receptor-binding function of the SARS-CoV-2 spike protein. The constant emergence of SARS-CoV-2 variants resulting from mutations in the receptor-binding domain (RBD) leads to vaccine immune evasion and underscores the importance of broadly acting COVID-19 vaccines. Inactivated whole virus vaccines can elicit broader immune responses to multiple epitopes of several antigens and help overcome such immune evasions. We prepared a psoralen-inactivated SARS-CoV-2 vaccine (SARS-CoV-2 PsIV) and evaluated its immunogenicity and efficacy in nonhuman primates (NHPs) when administered with the Advax-CpG adjuvant. We also evaluated the SARS-CoV-2 PsIV as a booster shot in animals vaccinated with a DNA vaccine that can express the full-length spike protein. The Advax-CpG-adjuvanted SARS-CoV-2 PsIV elicited a dose-dependent neutralizing antibody response in the NHPs, as measured using a serum microneutralization assay against the SARS-CoV-2 Washington strain and the Delta variant. The animals vaccinated with the DNA vaccine followed by a boosting dose of the SARS-CoV-2 PsIV exhibited the highest neutralizing antibody responses and were able to quickly clear infection after an intranasal challenge with the SARS-CoV-2 Delta variant. Overall, the data show that the Advax-CpG-adjuvanted SARS-CoV-2 PsIV, either by itself or as a booster shot following nucleic acid (NA) vaccines, has the potential to protect against emerging variants.

Original languageEnglish
Article number451
JournalVaccines
Volume12
Issue number5
DOIs
StatePublished - May 2024
Externally publishedYes

Keywords

  • Advax-CpG
  • conformational epitopes
  • COVID-19
  • DNA vaccine
  • SARS-CoV-2
  • SARS-CoV-2 neutralizing antibodies
  • SARS-CoV-2 PsIV

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