Covid-19 vaccines: Efficacy, safety and future prospects

ABSTRACT

SARS-CoV-2 still remains to be the cause of the Covid-19 pandemic, with more than 200 million infections and over 4.5 million deaths worldwide. With the onset of this pandemic, vaccine development efforts began on an unprecedented scale in the world, and it was seen that some vaccines received global application permissions in a very short period of time. For now, it has been proven that current COVID-19 vaccines are highly effective in protecting against serious illness and death. However, there remains much to learn about the immune response of vaccines and the duration of protection, and how we can further optimize vaccines against new variants. As of today, some inactivated vaccines (eg. Sinovac, Sinopharm, BharatBiotech), mRNA vaccines (eg.Pfizer&Bionthec, Moderna), Non-Replicating Viral Vector ones (eg. Oxford, Astra- Zeneca, Sputnik V) and recombinant protein vaccines (eg.Novovax) have been approved for immediate use, but determining the longterm effectiveness of vaccination with existing vaccines and moving towards adolescent and pediatric applications, as well as the reports on some serious side effects seen especially with mRNA and vector vaccines, remain important issues. In addition, the difficulties of poor countries' access to vaccines, and serious vaccine insecurity or rejection in almost all countries constitute major obstacles against the termination of the pandemic. The extension of the time required for the formation of herd immunity leads to the emergence of new variants. The rapid spread of these variants leading to a significant decrease in the effectiveness of the existing vaccines brings about a need for the modification of the current vaccines. During this period, we developed a different vaccine candidate and two vaccine formulations that can be easily adapted to emerging variants. In our study, a fragment protein (P1;MW 33 kDa) containing the Receptor-Binding Domain (RBD) in the spike S1 region, a fragment protein in the S2 region (P2;MW 17.6) and nucleocapsid protein (N;MW 46 kDa) were expressed in Escherichia coli, and subsequently the recombinant proteins were purified. It was determined that each of these three protein antigens reacted strongly with recovered Covid-19 patient sera. The combination of these three proteins was adsorbed with one adjuvant or two adjuvants led to the development of two formulations. In mouse immunization studies, these vaccine candidates elicited very high titers of anti-P1 IgG and IgG2a, anti-P2 IgG and IgG2a, and anti-N IgG and IgG2a. In the live virus neutralization assays, high virus neutralizing antibody levels were observed, and by obtaining specific interferon-gamma (INF-gamma) from immunized mouse splenocytes, we proved that a good cellular immunity was achieved too. These findings, overall, validated high immunogenicity of the P1 and P2 proteins of the S region and the N protein to order to develop an effective vaccine candidate against SARS CoV-2 infection. In addition, a variant recombinant protein was designed by our group and prepared in the same way. This protein that contains the most important point mutations of the known variants is being intended to be incorporated into our candidate vaccine. Our studies are being conducted in this direction and we aim at starting Phase I trials as soon as possible. In conclusion, such alterations/adaptations in vaccine formulations are highly important to optimize current vaccines. In order to reduce the worldwide effects of SARS-CoV-2 variants, it is necessary to develop new generation COVID-19 vaccines besides an urgent elimination of the vaccine inequality all over the world.