Safety Assessment of Co-Administered SARS-CoV-2 Vaccines in BALB/c Mice

Abstract

The onset of Coronavirus disease 2019 (COVID-19) in late 2019 presented a severe worldwide health crisis with widespread morbidity and mortality. Various vaccine platforms have been rapidly developed and approved for broad use in a swift and urgent response to prevent the transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. However, these vaccines differ significantly in terms of safety. Heterologous prime-boost vaccination enhances vaccine safety compared to homologous vaccination, although it could lead to a higher cumulative number of transient adverse events reported at each visit. Therefore, additional strategies are necessary to improve SARS- CoV-2 vaccine safety. Anecdotal options suggest that vaccine co-administration can significantly reduce these adverse effects and consequently, avert the need for frequent booster doses. This study reports the immunization outcomes against the SARS-CoV-2 virus by assessing the safety profiles of different SARS-CoV-2 vaccines co-administered in BALB/c mice. Vaccine combinations comprising mRNA/adenovirus26-vector, mRNA/inactivated, adenovirus26-vector/inactivated, and mRNA/adenovirus26-vector/inactivated vaccines were prepared in optimized doses, and their activities upon immunization evaluated in comparison with individual mRNA, adenovirus26-vectored and inactivated vaccines. Twenty-eight days post-immunization, safety profiles of the various treatments were evaluated through hematological and biochemical examination. Importantly, the co-administration regimens proved safe and were well-tolerated in mice, as evidenced by the normal hematological and biochemical values.