TY - JOUR
T1 - Immunogenicity of adjuvanted psoralen-inactivated sars-cov-2 vaccines and sars-cov-2 spike protein dna vaccines in balb/c mice
AU - Sundaram, Appavu K.
AU - Ewing, Daniel
AU - Liang, Zhaodong
AU - Jani, Vihasi
AU - Cheng, Ying
AU - Sun, Peifang
AU - Raviprakash, Kanakatte
AU - Wu, Shuenn Jue
AU - Petrovsky, Nikolai
AU - Defang, Gabriel
AU - Williams, Maya
AU - Porter, Kevin R.
N1 - Funding Information:
This work was funded by DHP RDT&E supplemental COVID funding. Development of Advax-2 adjuvant was supported by funding from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health to Vaxine Pty, Ltd., under Contracts HHS-N272201400053C, HHS-N272200800039C and U01-AI061142. We thank Qi Qiu (NMRC) for his help with ELISA assays.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/5
Y1 - 2021/5
N2 - 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.
AB - 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.
KW - 4-aminomethyl-4,5,8-trimethy lpsoralen (AMT)
KW - Advax-2
KW - Anti-SARS-CoV-2-neutralizing antibodies
KW - COVID-19
KW - Conformational epitopes of surface antigens
KW - DNA vaccine
KW - Prime-boost
KW - Psoralen-inactivated SARS-CoV-2 vaccine
KW - SARS-CoV-2
UR - http://www.scopus.com/inward/record.url?scp=85106995150&partnerID=8YFLogxK
U2 - 10.3390/pathogens10050626
DO - 10.3390/pathogens10050626
M3 - Article
AN - SCOPUS:85106995150
SN - 2076-0817
VL - 10
JO - Pathogens
JF - Pathogens
IS - 5
M1 - 626
ER -