Recombinant protein subunit SARS-CoV-2 vaccines formulated with CoVaccine HT™ adjuvant induce broad, Th1 biased, humoral and cellular immune responses in mice
Chih-Yun Lai,
Albert To,
Teri Ann S. Wong,
Michael M. Lieberman,
David E. Clements,
James T. Senda,
Aquena H. Ball,
Laurent Pessaint,
Hanne Andersen,
Wakako Furuyama,
Andrea Marzi,
Oreola Donini,
Axel T. Lehrer
Affiliations
Chih-Yun Lai
Department of Tropical Medicine, Medical Microbiology, and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, USA; Pacific Center for Emerging Infectious Disease Research, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, USA
Albert To
Department of Tropical Medicine, Medical Microbiology, and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, USA
Teri Ann S. Wong
Department of Tropical Medicine, Medical Microbiology, and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, USA
Michael M. Lieberman
Department of Tropical Medicine, Medical Microbiology, and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, USA
David E. Clements
Hawaii Biotech, Inc., Honolulu, HI, USA
James T. Senda
Hawaii Biotech, Inc., Honolulu, HI, USA
Aquena H. Ball
Department of Tropical Medicine, Medical Microbiology, and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, USA
Laurent Pessaint
Bioqual Inc., Rockville, MD, USA
Hanne Andersen
Bioqual Inc., Rockville, MD, USA
Wakako Furuyama
Laboratory of Virology, Division of Intramural Research, NIAID, NIH, Hamilton, Montana, MT, USA
Andrea Marzi
Laboratory of Virology, Division of Intramural Research, NIAID, NIH, Hamilton, Montana, MT, USA
Oreola Donini
Soligenix, Inc, Princetown, NJ, USA
Axel T. Lehrer
Department of Tropical Medicine, Medical Microbiology, and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, USA; Pacific Center for Emerging Infectious Disease Research, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, USA; Corresponding author at: University of Hawaii at Manoa, John A. Burns School of Medicine, Department of Tropical Medicine, 651 Ilalo Street, Honolulu, HI 96813, USA.
The speed at which several COVID-19 vaccines went from conception to receiving FDA and EMA approval for emergency use is an achievement unrivaled in the history of vaccine development. Mass vaccination efforts using the highly effective vaccines are currently underway to generate sufficient herd immunity and reduce transmission of the SARS-CoV-2 virus. Despite the most advanced vaccine technology, global recipient coverage, especially in resource-poor areas remains a challenge as genetic drift in naïve population pockets threatens overall vaccine efficacy. In this study, we described the production of insect-cell expressed SARS-CoV-2 spike protein ectodomain constructs and examined their immunogenicity in mice. We demonstrated that, when formulated with CoVaccine HTTM adjuvant, an oil-in-water nanoemulsion compatible with lyophilization, our vaccine candidates elicit a broad-spectrum IgG response, high neutralizing antibody (NtAb) titers against SARS-CoV-2 prototype and variants of concern, specifically B.1.351 (Beta) and P.1. (Gamma), and an antigen-specific IFN-γ secreting response in outbred mice. Of note, different ectodomain constructs yielded variations in NtAb titers against the prototype strain and some VOC. Dose response experiments indicated that NtAb titers increased with antigen dose, but not adjuvant dose, and may be higher with a lower adjuvant dose. Our findings lay the immunological foundation for the development of a dry-thermostabilized vaccine that is deployable without refrigeration.
