Immunogenicity of Adjuvanted Psoralen-Inactivated SARS-CoV-2 Vaccines and SARS-CoV-2 Spike Protein DNA Vaccines in BALB/c Mice.

Appavu K Sundaram,Kanakatte Raviprakash,Kevin R Porter,Peifang Sun,Gabriel Defang,Shuenn-Jue Wu,Vihasi Jani,Nikolai Petrovsky,Daniel Ewing,Ying Cheng,Maya Williams,Zhaodong Liang

doi:10.3390/pathogens10050626

Abstract

The development of a safe and effective vaccine to protect against COVID-19 is a global priority due to the current high SARS-CoV-2 infection rate. Currently, there are over 160 SARS-CoV-2 vaccine candidates at the clinical or pre-clinical stages of development. Of these, there are only three whole-virus vaccine candidates produced using β-propiolactone or formalin inactivation. Here, we prepared a whole-virus SARS-CoV-2 vaccine (SARS-CoV-2 PsIV) using a novel psoralen inactivation method and evaluated its immunogenicity in mice using two different adjuvants, alum and Advax-2. We compared the immunogenicity of SARS-CoV-2 PsIV against SARS-CoV-2 DNA vaccines expressing either full-length or truncated spike proteins. We also compared the psoralen-inactivated vaccine against a DNA prime, psoralen-inactivated vaccine boost regimen. After two doses, the psoralen-inactivated vaccine, when administered with alum or Advax-2 adjuvants, generated a dose-dependent neutralizing antibody responses in mice. Overall, the pattern of cytokine ELISPOT responses to antigen-stimulation observed in this study indicates that SARS-CoV-2 PsIV with the alum adjuvant promotes a Th2-type response, while SARS-CoV-2 PsIV with the Advax-2 adjuvant promotes a Th1-type response.

Highlights

IntroductionIn the past 20 years, three coronaviruses have crossed species barriers to infect humans and cause acute severe respiratory illness: severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003, Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, and SARS-CoV-2 in 2019 [1,2]
The immunogenicity of SARS-CoV-2 PsIV was evaluated by immunizing BALB/c mice with different doses of the vaccine in combination with either alum or Advax-2 as an adjuvant
Advax-2 is a delta inulin adjuvant formulated with CpG oligonucleotide that has been shown to improve the immunogenicity and efficacy of a number of vaccines in human clinical trials including against influenza and hepatitis B [19,20,21]

Summary

Introduction

In the past 20 years, three coronaviruses have crossed species barriers to infect humans and cause acute severe respiratory illness: severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003, Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, and SARS-CoV-2 in 2019 [1,2]. There have been more than 116 million cases of SARS-CoV-2 infections and more than 2.5 million deaths worldwide due to this pandemic [3]. SARS-CoV-2 infections in humans emerged in December 2019 and have since spread throughout the world, causing COVID-19. Though the majority of SARS-CoV-2infected patients exhibit a mild disease with recovery typically within two-to-three weeks, a significant number of patients manifest the severe form of the illness with increased mortality

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