ABSTRACT
Background. Although multiple COVID-19 vaccines are currently in use, emergence of novel SARS-CoV-2 variants with reduced neutralization raises concern of future vaccine escape. COVI-VAC™ is a live attenuated SARS-CoV-2 strain based on WA/1 being developed as an intranasal COVID-19 vaccine. COVI-VAC is attenuated through removal of the furin cleavage site and introduction of 283 silent, deoptimizing mutations that maintain viral amino acid sequence but slow viral replication in vivo by up to 5 logs. Notably, COVI-VAC presents all viral antigens in their native conformation and is not limited to spike. COVI-VAC demonstrated attenuation, immunogenicity and single dose protection in both the Syrian golden hamster and non-human primate models and currently in Phase 1 clinical trials. In this study, we evaluated efficacy of COVI-VAC against challenge with the Beta/B.1.351 variant in Syrian golden hamsters. Methods. Syrian golden hamsters, 7-10 weeks of age were, vaccinated intranasally with 8.25x104 PFU COVI-VAC (n=28) or vehicle control (n=16). Twenty seven days post-vaccination, animals were challenged intranasally with 3x104 PFU of wildtype (WT) SARS-CoV-2 Beta. Animals were weighed daily. Further analysis is being conducted with serum and key tissues from pre and post challenge timepoints to include neutralizing antibody, biodistribution (subgenomic qPCR) and histopathology. Results. COVI-VAC prevented weight loss following challenge with the heterologous variant of SARS-CoV-2, B.1.351/Beta (Figure). Results of additional analyses will be available before the IDWeek meeting. Change in Weight following SARS-CoV-2 Beta Challenge Conclusion. COVI-VAC is protective against heterologous challenge with SARSCoV-2 Beta. By presenting all viral antigens, COVI-VAC may be less affected by viral evolution than spike-based vaccines.
ABSTRACT
Background. COVI-VACTM is an intra-nasal live-attenuated SARS-COV-2 synthetic viral vaccine being developed for the prevention of COVID-19. COVI-VAC is attenuated through deletion of the furin cleavage site and introduction of 283 silent deoptimizing mutations that maintain viral amino acid sequence but result in significant attenuation due to slow translation in the human host cell. Notably, COVI-VAC includes all viral antigens and is not limited to spike. COVI-VAC has demonstrated attenuation, immunogenicity and single dose protection in both Syrian golden hamster and non-human primate models. Methods. 48 healthy young adults were enrolled in an inpatient quarantine setting to one of 3 dose escalating cohorts and randomized to COVI-VAC or saline placebo given as nose drops, as a single 0.5mL dose or 2 doses 28 days apart. Endpoints included solicited and unsolicited adverse events, serum cytokines, viral shedding and sequence stability, mucosal and serum antibody responses and IFN ELISpot. Subjects will be followed for 1 year for late safety events and durability of immune response. Results. Dosing is complete. There has been no trend in solicited reactogenicity events, and all unsolicited adverse events reported to date have been mild. There have been no SAEs or Grade 3 or 4 events. Vaccine virus from anonymized subjects was shed at levels lower than that likely to result in onward transmission, and the deoptimized sequence of the shed virus remained unchanged compared to the original vaccine sequence. Unblinded data including immunogenicity will be available prior to the IDWeek meeting. Conclusion. COVI-VAC appears safe and well tolerated in healthy young adults. Vaccination resulted in minimal viral shedding without sequence instability. Safety and shedding data supports continued development in a wider Phase 2/3 population.