Biological and Immune Responses to Current Anti-SARS-CoV-2 mRNA Vaccines beyond Anti-Spike Antibody Production

Abstract

Several vaccine strategies are now available to fight the current SARS-CoV-2 pandemic. Those based on the administration of lipid-complexed messenger(m)RNA molecules represent the last frontiers in terms of technology innovation. mRNA molecules coding for the SARS-CoV-2 Spike protein are intramuscularly injected, thereby entering cells by virtue of their encapsulation into synthetic lipid nanovesicles. mRNA-targeted cells express the Spike protein on their plasma membrane in a way that it can be sensed by the immune system, which reacts generating anti-Spike antibodies. Although this class of vaccines appears as the most effective against SARS-CoV-2 infection and disease, their safety and efficiency are challenged by several factors included, but not limited to the following: emergence of viral variants, lack of adequate pharmacokinetics/pharmacodynamics studies, inability to protect oral mucosa from infection, and antibody waning. Emergence of viral variants can be a consequence of mass vaccination carried out in a pandemic time using suboptimal vaccines against an RNA virus. On the other hand, understanding the remainder flaws could be of some help in designing next generation anti-SARS-CoV-2 vaccines. In this commentary, issues regarding the fate of injected mRNA, the tissue distribution of the induced antiviral antibodies, and the generation of memory B cells are discussed. Careful evaluation of both experimental and clinical observations on these key aspects should be taken into account before planning booster administration, vaccination to non-at-risk population, and social restrictions.

Figure 1

The “original antigenic sin.” When the body first encounters a pathogen, it produces effective antibodies against its dominant antigen and thus eliminates the pathogen. Selective pressure can originate pathogens with new dominant antigens, with the original antigens now being recessive. In this case, the immune system still produces the former antibodies against the old “now recessive antigen” and develops antibodies against the new dominant one scarcely. The results are the production of ineffective antibodies and generation of weak immunity.