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Article

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

1
Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, QC H3T 1E2, Canada
2
Division of Experimental Medicine, Department of Medicine, McGill University, Montréal, QC H4A 3J1, Canada
3
Division of Infectious Disease, Department of Medicine & Division of Medical Microbiology, Department of Clinical Laboratory Medicine, Jewish General Hospital, Montréal, QC H3T 1E2, Canada
*
Author to whom correspondence should be addressed.
Viruses 2018, 10(3), 100; https://doi.org/10.3390/v10030100
Received: 28 January 2018 / Revised: 22 February 2018 / Accepted: 23 February 2018 / Published: 27 February 2018
(This article belongs to the Special Issue Homage to Mark Wainberg)
Flagellin’s potential as a vaccine adjuvant has been increasingly explored over the last three decades. Monomeric flagellin proteins are the only known agonists of Toll-like receptor 5 (TLR5). This interaction evokes a pro-inflammatory state that impacts upon both innate and adaptive immunity. While pathogen associated molecular patterns (PAMPs) like flagellin have been used as stand-alone adjuvants that are co-delivered with antigen, some investigators have demonstrated a distinct advantage to incorporating antigen epitopes within the structure of flagellin itself. This approach has been particularly effective in enhancing humoral immune responses. We sought to use flagellin as both scaffold and adjuvant for HIV gp41 with the aim of eliciting antibodies to the membrane proximal external region (MPER). Accordingly, we devised a straightforward step-wise approach to select flagellin-antigen fusion proteins for gene-based vaccine development. Using plasmid DNA vector-based expression in mammalian cells, we demonstrate robust expression of codon-optimized full length and hypervariable region-deleted constructs of Salmonella enterica subsp. enterica serovar Typhi flagellin (FliC). An HIV gp41 derived sequence including the MPER (gp41607–683) was incorporated into various positions of these constructs and the expressed fusion proteins were screened for effective secretion, TLR5 agonist activity and adequate MPER antigenicity. We show that incorporation of gp41607–683 into a FliC-based scaffold significantly augments gp41607–683 immunogenicity in a TLR5 dependent manner and elicits modest MPER-specific humoral responses in a mouse model. View Full-Text
Keywords: HIV-1; gp41; membrane proximal external region; MPER; flagellin; adjuvant; DNA vaccine HIV-1; gp41; membrane proximal external region; MPER; flagellin; adjuvant; DNA vaccine
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MDPI and ACS Style

Ajamian, L.; Melnychuk, L.; Jean-Pierre, P.; Zaharatos, G.J. DNA Vaccine-Encoded Flagellin Can Be Used as an Adjuvant Scaffold to Augment HIV-1 gp41 Membrane Proximal External Region Immunogenicity. Viruses 2018, 10, 100. https://doi.org/10.3390/v10030100

AMA Style

Ajamian L, Melnychuk L, Jean-Pierre P, Zaharatos GJ. DNA Vaccine-Encoded Flagellin Can Be Used as an Adjuvant Scaffold to Augment HIV-1 gp41 Membrane Proximal External Region Immunogenicity. Viruses. 2018; 10(3):100. https://doi.org/10.3390/v10030100

Chicago/Turabian Style

Ajamian, Lara, Luca Melnychuk, Patrick Jean-Pierre, and Gerasimos J. Zaharatos 2018. "DNA Vaccine-Encoded Flagellin Can Be Used as an Adjuvant Scaffold to Augment HIV-1 gp41 Membrane Proximal External Region Immunogenicity" Viruses 10, no. 3: 100. https://doi.org/10.3390/v10030100

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