Glycosylation as a key parameter in the design of nucleic acid vaccines

Vaccine-induced immunity is expected to target the native antigens expressed by the pathogens. Therefore, it is highly important to generate vaccine antigens that are immunologically indistinguishable from the native antigens. Nucleic acid vaccines, comprised of DNA, mRNA, or recombinant viral vector vaccines, introduce the genetic material encoding the antigenic protein for the host to express. Because these proteins will undergo host posttranslational modifications, host glycosylation can potentially alter the structure and immunological efficacy of the antigen. In this review, we discuss the potential impact of host protein glycosylation on the immune responses generated by nucleic acid vaccines against bacterial and viral pathogens. •Nucleic acid vaccines encoding antigenic proteins use host glycosylation machinery.•Unnaturally glycosylated bacterial antigens induce impaired immunity.•Glycans on viral glycoproteins may shield polypeptide B and/or T cell epitopes.•Viral glycopeptides may comprise the antigenic determinants or T cell epitopes.