COVID-19 Vaccine Development - where do we stand?

The COVID-19 pandemic and its high mortality rate is pushing health care systems to the edge and it is still too early to fully comprehend its socioeconomical impact. Global joint efforts have been undertaken to develop preventive vaccines that protect from severe disease and death. By October 15, 2021, the World Health Organization had approved six different vaccines using three platforms and nearly half of the world’s population had received at least one dose of these or similar vaccines, although they were mostly allocated to high and middle-income countries. Besides traditional vaccine platforms using inactivated virus or adjuvanted proteins, two more innovative platforms had been employed, that are mRNA and viral vectors vaccines. Safety profiles for these candidates showed higher reactogenicity, with systemic reactions that were rarely observed with inactivated vaccines. Post-authorization surveillance data revealed associations of mild myocarditis and pericarditis with mRNA vaccines, and thrombotic events and rare cases of Guillain-Barré-syndrome with viral vector vaccines. In terms of efficacy in phase III clinical trials, mRNA vaccines showed an exceptional efficacy of 95% in preventing SARS-CoV-2 infection, and comparable rates against severe disease or death. With viral vector vaccines, efficacy in preventing infection was lower, but similar for hospitalizations. Analogous results for inactivated vaccines came mostly only from participants younger than 65 years. With the emergence of new SARS-CoV-2 variants, especially the predominant Delta variant, and with waning immunity, efficacy in the protection against infection, but not against severe disease, decreased. This related to a reduction in binding antibody titers with time, a decrease in neutralizing capacity against variants, but stable T-cell responses that were less susceptible than antibodies to mutations found in circulating variants. Furthermore, distinct immune responses to different platforms were found and corroborated the assumption that neutralizing antibodies are important in protecting from infection, whereas cellular immune responses have a role in the prevention of severe disease. Current challenges with COVID-19 vaccines are, for example, optimized vaccines for vulnerable populations to meet their distinct requirements, such as a third dose for solid organ transplant recipients as catch-up vaccination for the considerable number of non-responders. Furthermore, there is a need for safe and effective vaccines for maternal vaccination during pregnancy that induce high antibody titers to directly protect the mother and to transfer protection to the newborn. Or last, the risk-benefit assessment for childhood vaccination and the demand to define the aim of vaccinating a population with to date a low risk of severe disease. In the near future, more understanding is necessary regarding heterologous boosts, which is combining different vaccine platforms, and the comprehension of requirements for sterilizing immunity with the development of mucosal vaccines or natural breakthrough infection on the way from a pandemic to an endemic. In summary, the rapid design of safe and effective COVID-19 vaccines is a historical success story and continuous work is needed to improve global vaccine distribution, establishing vaccine schedules for the various vaccine platforms and responding to specific requirements in vulnerable populations