A Whole Virion Vaccine for COVID-19 Produced via a Novel Inactivation Method and Preliminary Demonstration of Efficacy in an Animal Challenge Model

Abstract

The COVID-19 pandemic has generated intense interest in the rapid development and evaluation of vaccine candidates for this disease and other emerging diseases. Several novel methods for preparing vaccine candidates are currently undergoing clinical evaluation in response to the urgent need to prevent the spread of COVID-19. In many cases, these methods rely on new approaches for vaccine production and immune stimulation. We report on the use of a novel method (SolaVAX) for production of an inactivated vaccine candidate and the testing of that candidate in a hamster animal model for its ability to prevent infection upon challenge with SARS-CoV-2 virus. The studies employed in this work included an evaluation of the levels of neutralizing antibody produced post-vaccination, levels of specific antibody sub-types to RBD and spike protein that were generated, evaluation of viral shedding post-challenge, flow cytometric and single cell sequencing data on cellular fractions and histopathological evaluation of tissues post-challenge. The results from this preliminary evaluation provide insight into the immunological responses occurring as a result of vaccination with the proposed vaccine candidate and the impact that adjuvant formulations, specifically developed to promote Th1 type immune responses, have on vaccine efficacy and protection against infection following challenge with live SARS-CoV-2. This data may have utility in the development of effective vaccine candidates broadly. Furthermore, the results of this preliminary evaluation suggest that preparation of a whole virion vaccine for COVID-19 using this specific photochemical method may have potential utility in the preparation of one such vaccine candidate.

Inactivated whole hepatitis C virus vaccine employing a licensed adjuvant elicits cross-genotype neutralizing antibodies in mice

“…In this study, antigen doses were defined by infectious unit equivalents, as infectivity titrations were used to monitor viral processing, providing evidence for presence of intact particles, and as reported by others. 56,57 This might not allow an optimal comparison of amounts of particles for viruses showing different specific infectivities. Therefore, we retrospectively determined amounts of HCV Core and genome copies in vaccine preparations.…”

Covax-19/Spikogen® vaccine based on recombinant spike protein extracellular domain with Advax-CpG55.2 adjuvant provides single dose protection against SARS-CoV-2 infection in hamsters

“…We next sought to assess the efficacy of the down-selected vaccine candidate, which was now named Covax-19®/Spikogen®, against viral replication/shedding and prevention of disease pathology in the well-established hamster model [26] , [28] . The candidate ECD vaccine was compared against the FL protein and the Advax-CpG adjuvant was compared to the alum-CpG adjuvant formulation.…”

SARS-CoV-2 Production in a Scalable High Cell Density Bioreactor

“…Assuming a vaccine dose of 7 log 10 TCID 50 or 1 ug S1 and 50% loss in downstream processing, approximately 1500 doses could be obtained from one CelCradle TM 500-AP culture (1 dose / 3 mL bioreactor harvest) and several hundred thousand vaccine doses could potentially be obtained from a 100 L TideXcell bioreactor. Assumptions on the vaccine dose are based on data for other antiviral vaccines [ 36 , 37 , 58 , 59 , 60 , 61 , 62 ] and observations from preliminary immunogenicity studies in mice (unpublished). Virus manufacturing based on the described and similar processes might be of interest for inactivated but also attenuated second-generation COVID-19 vaccines [ 63 , 64 ].…”