CoVaccine HT™ adjuvant potentiates robust immune responses to recombinant SARS-CoV-2 Spike S1 immunisation

Abstract

The current COVID-19 pandemic has claimed hundreds of thousands of lives and its causative agent, SARS-CoV-2, has infected millions, globally. The highly contagious nature of this respiratory virus has spurred massive global efforts to develop vaccines at record speeds. In addition to enhanced immunogen delivery, adjuvants may greatly impact protective efficacy of a SARS-CoV-2 vaccine. To investigate adjuvant suitability, we formulated protein subunit vaccines consisting of the recombinant S1 domain of SARS-CoV-2 Spike protein alone or in combination with either CoVaccine HT™ or Alhydrogel. CoVaccine HT™ induced high titres of antigen-binding IgG after a single dose, facilitated affinity maturation and class switching to a greater extent than Alhydrogel and elicited potent cell-mediated immunity as well as virus neutralising antibody titres. Data presented here suggests that adjuvantation with CoVaccine HT™ can rapidly induce a comprehensive and protective immune response to SARS-CoV-2.

CoVaccine HT™ Adjuvant Potentiates Robust Immune Responses to Recombinant SARS-CoV-2 Spike S1 Immunization

“…We would further like to acknowledge partial funding for these studies from R01AI132323 (National Institute of Allergy and Infectious Diseases), from P30GM114737 (Centers of Biomedical Research Excellence, National Institute of General Medical Sciences) and institutional funds. This manuscript has been released as a pre-print at BioR x iv (53).…”

Recombinant protein subunit SARS-CoV-2 vaccines formulated with CoVaccine HT adjuvant induce broad, Th1 biased, humoral and cellular immune responses in mice

“…Previous preclinical studies of SARS-CoV and MERS-CoV vaccines have demonstrated that the S protein plays a key role in induction of neutralizing antibody and T cell responses as well as protective immunity [16][17][18]. Stabilization of S proteins in the prefusion trimeric conformation results in increased expression, conformational homogeneity, and production of potent neutralizing antibody responses [18,27]. Current SARS-CoV-2 vaccines under development use either RBD or full-length S protein with or without modifications for stabilization of prefusion conformation as the major antigen targets.…”

“…Based on previous preclinical studies of vaccines against the highly pathogenic SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV) [16][17][18] as well as recent studies of patients with SARS-CoV-2 infections [19][20][21][22], S protein appears to be the antigenic target of both neutralizing antibody and T cell responses. The majority of current COVID-19 vaccines under preclinical and clinical development use full-length S proteins as antigen targets with further modifications such as removal of the polybasic sites [23][24][25], introduction of proline mutations [23,26,27], or addition of trimerization domains to preserve the native-like trimeric prefusion structure of S proteins. These antigens have been shown to mimic the native S protein presented on viral particles and preserve neutralizationsensitive epitopes [18,28].…”

Development of COVID-19 Recombinant Subunit Vaccine and Adjuvant

“…Compared with the aluminum adjuvant that lacks the ability to mediate cellular immunity, the emulsion adjuvant can trigger a more balanced immune response by improving antigen uptake, recruiting immune cells, and promoting the activation and migration of antigen presenting cells. An experiment at the University of Hawaii in the United States evaluated the immune effect of Covaccine HT adjuvant compounded with S1 subunit of spike protein of novel coronavirus [6]. The experimental results showed that after immunizing mice for a single time (day 14), serum antibody analysis showed that the specific IgG antibody titer of Covac group was significantly higher than that of aluminum adjuvant group (the titer level of aluminum adjuvant group was close to the baseline), and the results of microsphere immunoassay data also confirmed that immunization with S1 subunit of COVID-19 and Covaccine HT adjuvant could induce a high level of antigen-specific IgG response.…”