Next Article in Journal
Modulating Vaccinia Virus Immunomodulators to Improve Immunological Memory
Next Article in Special Issue
AIDS Clinical Research in Spain—Large HIV Population, Geniality of Doctors, and Missing Opportunities
Previous Article in Journal
Time Intervals in Sequence Sampling, Not Data Modifications, Have a Major Impact on Estimates of HIV Escape Rates
Previous Article in Special Issue
Blood Mitochondrial DNA Content in HIV-Exposed Uninfected Children with Autism Spectrum Disorder
Article Menu
Issue 3 (March) cover image

Export Article

Open AccessArticle
Viruses 2018, 10(3), 100; https://doi.org/10.3390/v10030100

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.
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)
Full-Text   |   PDF [3772 KB, uploaded 27 February 2018]   |  

Abstract

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
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

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.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Viruses EISSN 1999-4915 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top