Cognizance of posttranslational modifications in vaccines: A way to enhanced immunogenicity

Abstract

Vaccination is a significant advancement or preventative strategy for controlling the spread of various severe infectious and noninfectious diseases. The purpose of vaccination is to stimulate or activate the immune system by injecting antigens, i.e., either whole microorganisms or using the pathogen's antigenic part or macromolecules. Over time, researchers have made tremendous efforts to reduce vaccine side effects or failure by developing different strategies combining with immunoinformatic and molecular biology. These newly designed vaccines are composed of single or several antigenic molecules derived from a pathogenic organism. Although, whole-cell vaccines are still in use against various diseases but due to their ineffectiveness, other vaccines like DNA-based, RNA-based, and protein-based vaccines, with the addition of immunostimulatory agents, are in the limelight. Despite this, many researchers escape the most common fundamental phenomenon of protein posttranslational modifications during the development of vaccines, which regulates protein functional behavior, evokes immunogenicity and stability, etc. The negligence about post translational modification (PTM) during vaccine development may affect the vaccine's efficacy and immune responses. Therefore, it becomes imperative to consider these modifications of macromolecules before finalizing the antigenic vaccine construct. Here, we have discussed different types of posttranslational/transcriptional modifications that are usually considered during vaccine construct designing: Glycosylation, Acetylation, Sulfation, Methylation, Amidation, SUMOylation, Ubiquitylation, Lipidation, Formylation, and Phosphorylation. Based on the available research information, we firmly believe that considering these modifications will generate a potential and highly immunogenic antigenic molecule against communicable and noncommunicable diseases compared to the unmodified macromolecules.

Keywords: immunogenicity; infectious diseases; noninfectious diseases; posttranslational modifications; vaccines.

Figure 1

Pictorial representation of posttranslational modifications in a cell, through natural process or synthesized chemically by various enzymatic reactions. (A) Cell (where protein biosynthesis occurs via ribosomes). (B) Types of posttranslational modifications essentially considered for vaccine designing (enzymatic/chemical modifications of proteins). (C) Example of phosphorylation (enzymatic reaction of PTM)

Figure 2

Antigenic representation of vaccine candidate through MHC complexes. The internalized antigenic protein with posttranslational modification is processed into the peptides and presented through the MHC complex on APCs' surface, further recognized through respective CD4+ and CD8+ T‐cells. APC,(Antigen‐presenting cell); HLA, human leukocyte antigen; MHC, major histocompatibility complex; MIIC, MHC Class II compartment; TCR, T‐lymphocyte cell receptor