Modelos animais na elaboração de vacinas contra a Covid-19: metanálise dos desfechos pré-clínicos

Abstract

The COVID-19 pandemic has been considered the main cause of respiratory disease and deaths over the world in the last years, particularly in risk groups. The disease, caused by the SARS-CoV-2, became a Public Health emergency of international importance. Therefore, development of vaccines was urgently needed to control the ongoing pandemic COVID-19. Consequently, animal models have been widely tested for accelerating the development of effective and safe vaccines. Herein, a systematic review and a meta-analysis was carried out to identify pre-clinical outcomes of studies using animal models for developing COVID-19 vaccines based on the PubMed, SCOPUS, Embase, OVID, Cochrane, Science Direct, LILACS e EBSCO databases. “Animal models; pre-clinical studies; vaccines; immunization; SARS-CoV- 2; COVID-19” keywords were used as search strategy. Inclusion criteria were pre-clinical studies, involving studies of vaccine tests against SARS-CoV-2 in vivo animal models, with at least 2 doses of vaccine, published from 2020 to 2021. The quality of scientific evidence in the studies addressed was classified as high, moderate, low, or very low, according to the GRADE rules and the risk of bias according to the Cochrane instrument. Nineteen important preclinical studies of vaccine tests in animal models were found of the total of 326 identified studies. The studies evaluated showed the high quality of scientific evidence, with an average degree of confidence and recommendation of 75%. Furthermore, the analysed studies showed high homogeneity in the results, presenting 98.95% (I2) to studies with larger sample size. The results showed ten outstanding vaccines with a degree of confidence and recommendation that ranged from 85% to 95%, and of these ten vaccines, five vaccines showed a degree of confidence and recommendation of 95%, most of them coming from technological manufacturing protocols, such as the BNT162b1 and BNT162b2 vaccines, the DNA vaccine encoding the full-length Spike (S) protein of SARS-CoV-2, and a recombinant S1 protein vaccine, the S-Trimer vaccine, and Nanocovax. It was evidenced that safety and efficacy are determined by the number of animals involved, the use of a randomized control group, and the follow-up time of the studies