Low toxicity and high immunogenicity of an inactivated vaccine candidate against COVID-19 in different animal models

Abstract

The ongoing COVID-19 pandemic is causing huge impact on health, life and global economy which is characterized by rapid spreading of SARS-CoV-2, high number of confirmed cases and a fatality/case rate worldwide reported by WHO. The most effective intervention measure will be to develop safe and effective vaccines to protect the population from the disease and limit the spread of the virus. An inactivated, whole virus vaccine candidate of SARS-CoV-2 has been developed by Wuhan Institute of Biological Products and Wuhan Institute of Virology. The low toxicity, immunogenicity and immune persistence were investigated in preclinical studies using 7 different species of animals. The results showed that the vaccine candidate was well tolerated and stimulated high levels of specific IgG and neutralizing antibodies. Low or no toxicity in three species of animals was also demonstrated in preclinical study of the vaccine candidate. Biochemical analysis of structural proteins and purity analysis were performed. The inactivated, whole virion vaccine was characterized with safe double-inactivation, no use of DNases and high purity. Dosages, boosting times, adjuvants, and immunization schedules were shown to be important for stimulating a strong humoral immune response in animals tested. Preliminary observation in ongoing phase I and II clinical trials of the vaccine candidate in Wuzhi County, Henan Province, showed that the vaccine is well tolerant. The results were characterized by very low proportion and low degree of side effects, high levels of neutralizing antibodies and seroconversion. These results consistent with the results obtained from preclinical data on the safety.

Development and pre-clinical evaluation of Newcastle disease virus-vectored SARS-CoV-2 intranasal vaccine candidate

“…Likewise, no visible lesions were observed in the nasal area, the site of administration of the vaccine candidate, nor any notable clinical symptom or evidence of mortality was recorded. These results are comparable with those obtained in the different pre-clinical studies of currently available SARS-CoV-2 vaccines 83 .…”

SARS-CoV-2 inactivated vaccine (Vero cells) shows good safety in repeated administration toxicity test of Sprague Dawley rats

“…Sprague Dawley rats were used in this study for repeated dose study as well. After different doses administration and 2-week recovery, there was no obvious systemic toxicity observed in rats ( Wang et al, 2020 ). Similar to the study above, repeated administration of high-dose (1.5 person dosages) SARS-CoV-2 inactivated vaccine did not cause damage to the animals’ immune system, and no obvious dose-response histopathological changes were seen in various tissues and organs.…”

Long-term humoral immunogenicity, safety and protective efficacy of inactivated vaccine against COVID-19 (CoviVac) in preclinical studies

“…Moreover, the observed immunohistochemical changes and weight loss patterns in hamsters resemble the course of mild SARS-CoV-2 infection in humans [ 34 ]. A number of works showed the validity of Syrian hamster model to be used for studies of protective efficacy of NAbs and vaccines against SARS-CoV-2 [ 35–44 ], although the pneumonia signs were fast developing and severe.…”