DNA Vaccine-Encoded Flagellin Can Be Used as an Adjuvant Scaffold to Augment HIV-1 gp41 Membrane Proximal External Region Immunogenicity.

摘要: Flagellin’s potential as a vaccine adjuvant has been increasingly explored over the last three decades. Monomeric flagellin proteins are only known agonists of Toll-like receptor 5 (TLR5). This interaction evokes pro-inflammatory state that impacts upon both innate and adaptive immunity. While pathogen associated molecular patterns (PAMPs) like have used stand-alone adjuvants co-delivered with antigen, some investigators demonstrated distinct advantage to incorporating antigen epitopes within structure itself. approach particularly effective in enhancing humoral immune responses. We sought use scaffold for HIV gp41 aim eliciting antibodies membrane proximal external region (MPER). Accordingly, we devised straightforward step-wise select flagellin-antigen fusion gene-based development. Using plasmid DNA vector-based expression mammalian cells, demonstrate robust codon-optimized full length hypervariable region-deleted constructs Salmonella enterica subsp. serovar Typhi (FliC). An derived sequence including MPER (gp41607–683) was incorporated into various positions these expressed were screened secretion, TLR5 agonist activity adequate antigenicity. show incorporation gp41607–683 FliC-based significantly augments immunogenicity dependent manner elicits modest MPER-specific responses mouse model.