Skip to main content
Top
Published in: AIDS Research and Therapy 1/2017

Open Access 01-12-2017 | Review

Development of an HIV vaccine using a vesicular stomatitis virus vector expressing designer HIV-1 envelope glycoproteins to enhance humoral responses

Authors: Trina Racine, Gary P. Kobinger, Eric J. Arts

Published in: AIDS Research and Therapy | Issue 1/2017

Login to get access

Abstract

Vesicular stomatitis virus (VSV), like many other Rhabdoviruses, have become the focus of intense research over the past couple of decades based on their suitability as vaccine vectors, transient gene delivery systems, and as oncolytic viruses for cancer therapy. VSV as a vaccine vector platform has multiple advantages over more traditional viral vectors including low level, non-pathogenic replication in diverse cell types, ability to induce both humoral and cell-mediate immune responses, and the remarkable expression of foreign proteins cloned into multiple intergenic sites in the VSV genome. The utility and safety of VSV as a vaccine vector was recently demonstrated near the end of the recent Ebola outbreak in West Africa where VSV pseudotyped with the Ebola virus (EBOV) glycoprotein was proven safe in humans and provided protective efficacy against EBOV in a human phase III clinical trial. A team of Canadian scientists, led by Dr. Gary Kobinger, is now working with International AIDS Vaccine Initiative (IAVI) in developing a VSV-based HIV vaccine that will combine unique Canadian research on the HIV-1 Env glycoprotein and on the VSV vaccine vector. The goal of this collaboration is to develop a vaccine with a robust and potent anti-HIV immune response with an emphasis on generating quality antibodies to protect against HIV challenges.
Literature
2.
go back to reference Flynn NM, Forthal DN, Harro CD, Judson FN, Mayer KH, Para MF, rgp120 HIV Vaccine Study Group. Placebo-controlled phase 3 trial of a recombinant glycoprotein 120 vaccine to prevent HIV-1 infection. J Infect Dis. 2005;191(5):654–65.CrossRefPubMed Flynn NM, Forthal DN, Harro CD, Judson FN, Mayer KH, Para MF, rgp120 HIV Vaccine Study Group. Placebo-controlled phase 3 trial of a recombinant glycoprotein 120 vaccine to prevent HIV-1 infection. J Infect Dis. 2005;191(5):654–65.CrossRefPubMed
3.
go back to reference Pitisuttithum P, Gilbert P, Gurwith M, Heyward W, Martin M, van Griensven F, et al. Randomized, double-blind, placebo-controlled efficacy trial of a bivalent recombinant glycoprotein 120 HIV-1 vaccine among injection drug users in Bangkok, Thailand. J Infect Dis. 2006;194(12):1661–71.CrossRefPubMed Pitisuttithum P, Gilbert P, Gurwith M, Heyward W, Martin M, van Griensven F, et al. Randomized, double-blind, placebo-controlled efficacy trial of a bivalent recombinant glycoprotein 120 HIV-1 vaccine among injection drug users in Bangkok, Thailand. J Infect Dis. 2006;194(12):1661–71.CrossRefPubMed
4.
go back to reference Hammer SM, Sobieszczyk ME, Janes H, Karuna ST, Mulligan MJ, Grove D, et al. Efficacy trial of a DNA/rAd5 HIV-1 preventive vaccine. N Engl J Med. 2013;369(22):2083–92.CrossRefPubMedPubMedCentral Hammer SM, Sobieszczyk ME, Janes H, Karuna ST, Mulligan MJ, Grove D, et al. Efficacy trial of a DNA/rAd5 HIV-1 preventive vaccine. N Engl J Med. 2013;369(22):2083–92.CrossRefPubMedPubMedCentral
5.
go back to reference Letvin NL, Rao SS, Montefiori DC, Seaman MS, Sun Y, Lim SY, et al. Immune and genetic correlates of vaccine protection against mucosal infection by SIV in monkeys. Sci Transl Med. 2011;3(81):81ra36.CrossRefPubMedPubMedCentral Letvin NL, Rao SS, Montefiori DC, Seaman MS, Sun Y, Lim SY, et al. Immune and genetic correlates of vaccine protection against mucosal infection by SIV in monkeys. Sci Transl Med. 2011;3(81):81ra36.CrossRefPubMedPubMedCentral
6.
go back to reference Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, Kaewkungwal J, Chiu J, Paris R, et al. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med. 2009;361(23):2209–20.CrossRefPubMed Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, Kaewkungwal J, Chiu J, Paris R, et al. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med. 2009;361(23):2209–20.CrossRefPubMed
7.
go back to reference Haynes BF, Gilbert PB, McElrath MJ, Zolla-Pazner S, Tomaras GD, Alam SM, et al. Immune-correlates analysis of an HIV-1 vaccine efficacy trial. N Engl J Med. 2012;366(14):1275–86.CrossRefPubMedPubMedCentral Haynes BF, Gilbert PB, McElrath MJ, Zolla-Pazner S, Tomaras GD, Alam SM, et al. Immune-correlates analysis of an HIV-1 vaccine efficacy trial. N Engl J Med. 2012;366(14):1275–86.CrossRefPubMedPubMedCentral
8.
go back to reference Liu J, Ghneim K, Sok D, Bosche WJ, Li Y, Chipriano E, et al. Antibody-mediated protection against SHIV challenge includes systemic clearance of distal virus. Science. 2016;353(6303):1045–9.CrossRefPubMedPubMedCentral Liu J, Ghneim K, Sok D, Bosche WJ, Li Y, Chipriano E, et al. Antibody-mediated protection against SHIV challenge includes systemic clearance of distal virus. Science. 2016;353(6303):1045–9.CrossRefPubMedPubMedCentral
9.
go back to reference Moldt B, Le KM, Carnathan DG, Whitney JB, Schultz N, Lewis MG, et al. Neutralizing antibody affords comparable protection against vaginal and rectal simian/human immunodeficiency virus challenge in macaques. AIDS. 2016;30(10):1543–51.CrossRefPubMedPubMedCentral Moldt B, Le KM, Carnathan DG, Whitney JB, Schultz N, Lewis MG, et al. Neutralizing antibody affords comparable protection against vaginal and rectal simian/human immunodeficiency virus challenge in macaques. AIDS. 2016;30(10):1543–51.CrossRefPubMedPubMedCentral
10.
go back to reference Agnandji ST, Huttner A, Zinser ME, Njuguna P, Dahlke C, Fernandes JF, et al. Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe. N Engl J Med. 2016;374(17):1647–60.CrossRefPubMed Agnandji ST, Huttner A, Zinser ME, Njuguna P, Dahlke C, Fernandes JF, et al. Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe. N Engl J Med. 2016;374(17):1647–60.CrossRefPubMed
11.
go back to reference Henao-Restrepo AM, Camacho A, Longini IM, Watson CH, Edmunds WJ, Egger M, et al. Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ça Suffit!). Lancet. 2016. Henao-Restrepo AM, Camacho A, Longini IM, Watson CH, Edmunds WJ, Egger M, et al. Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ça Suffit!). Lancet. 2016.
12.
go back to reference Buchbinder SP, Mehrotra DV, Duerr A, Fitzgerald DW, Mogg R, Li D, et al. Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the step study): a double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet. 2016;372(9653):1881–93.CrossRef Buchbinder SP, Mehrotra DV, Duerr A, Fitzgerald DW, Mogg R, Li D, et al. Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the step study): a double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet. 2016;372(9653):1881–93.CrossRef
13.
go back to reference Parks C. G-106 Mucosal vaccination with a replication-competent VSV-HIV chimera delivering Env trimers protects rhesus macaques from rectal SHIV infection. JAIDS J Acquir Immune Defic Syndr. 2017;74:58.CrossRef Parks C. G-106 Mucosal vaccination with a replication-competent VSV-HIV chimera delivering Env trimers protects rhesus macaques from rectal SHIV infection. JAIDS J Acquir Immune Defic Syndr. 2017;74:58.CrossRef
14.
go back to reference Parks C. Protection from Rectal SHIV Infection Induced by Mucosal Vaccination with a Replication-competent VSV-HIV Chimera Delivering Env Trimers (Symposium Presentation). HIVR4P October 18, 2016. Chicago, Il, USA. Parks C. Protection from Rectal SHIV Infection Induced by Mucosal Vaccination with a Replication-competent VSV-HIV Chimera Delivering Env Trimers (Symposium Presentation). HIVR4P October 18, 2016. Chicago, Il, USA.
15.
go back to reference Rabinovich S, Powell RL, Lindsay RW, Yuan M, Carpov A, Wilson A, et al. A novel, live-attenuated vesicular stomatitis virus vector displaying conformationally intact, functional HIV-1 envelope trimers that elicits potent cellular and humoral responses in mice. PLoS ONE. 2014;9(9):e106597.CrossRefPubMedPubMedCentral Rabinovich S, Powell RL, Lindsay RW, Yuan M, Carpov A, Wilson A, et al. A novel, live-attenuated vesicular stomatitis virus vector displaying conformationally intact, functional HIV-1 envelope trimers that elicits potent cellular and humoral responses in mice. PLoS ONE. 2014;9(9):e106597.CrossRefPubMedPubMedCentral
16.
go back to reference Roberts A, Kretzschmar E, Perkins AS, Forman J, Price R, Buonocore L, et al. Vaccination with a recombinant vesicular stomatitis virus expressing an influenza virus hemagglutinin provides complete protection from influenza virus challenge. J Virol. 1998;72(6):4704–11.PubMedPubMedCentral Roberts A, Kretzschmar E, Perkins AS, Forman J, Price R, Buonocore L, et al. Vaccination with a recombinant vesicular stomatitis virus expressing an influenza virus hemagglutinin provides complete protection from influenza virus challenge. J Virol. 1998;72(6):4704–11.PubMedPubMedCentral
17.
go back to reference Ezelle HJ, Dubravka M, Barber GN. Generation of Hepatitis C virus-like particles by use of a recombinant vesicular stomatitis virus vector. J Virol. 2002;76(23):12325–34.CrossRefPubMedPubMedCentral Ezelle HJ, Dubravka M, Barber GN. Generation of Hepatitis C virus-like particles by use of a recombinant vesicular stomatitis virus vector. J Virol. 2002;76(23):12325–34.CrossRefPubMedPubMedCentral
18.
go back to reference Takada A, Robison C, Goto H, Sanchez A, Murti KG, Whitt MA, et al. A system for functional analysis of Ebola virus glycoprotein. Proc Natl Acad Sci USA. 1997;94(26):14764–9.CrossRefPubMedPubMedCentral Takada A, Robison C, Goto H, Sanchez A, Murti KG, Whitt MA, et al. A system for functional analysis of Ebola virus glycoprotein. Proc Natl Acad Sci USA. 1997;94(26):14764–9.CrossRefPubMedPubMedCentral
19.
go back to reference Garbutt M, Liebscher R, Wahl-Jensen V, Jones S, Moller P, Wagner R, et al. Properties of replication-competent vesicular stomatitis virus vectors expressing glycoproteins of filoviruses and arenaviruses. J Virol. 2004;78(10):5458–65.CrossRefPubMedPubMedCentral Garbutt M, Liebscher R, Wahl-Jensen V, Jones S, Moller P, Wagner R, et al. Properties of replication-competent vesicular stomatitis virus vectors expressing glycoproteins of filoviruses and arenaviruses. J Virol. 2004;78(10):5458–65.CrossRefPubMedPubMedCentral
20.
go back to reference Jones SM, Feldmann H, Stroher U, Geisbert JB, Fernando L, Grolla A, et al. Live attenuated recombinant vaccine protects nonhuman primates against Ebola and Marburg viruses. Nat Med. 2005;11(7):786–90.CrossRefPubMed Jones SM, Feldmann H, Stroher U, Geisbert JB, Fernando L, Grolla A, et al. Live attenuated recombinant vaccine protects nonhuman primates against Ebola and Marburg viruses. Nat Med. 2005;11(7):786–90.CrossRefPubMed
21.
go back to reference ElSherif MS, Brown C, MacKinnon-Cameron D, Li L, Racine T, Alimonti J, et al. Assessing the safety and immunogenicity of recombinant vesicular stomatitis virus Ebola vaccine in healthy adults: a randomised clinical trial. CMAJ. 2017;189(24):E819–27.CrossRefPubMedPubMedCentral ElSherif MS, Brown C, MacKinnon-Cameron D, Li L, Racine T, Alimonti J, et al. Assessing the safety and immunogenicity of recombinant vesicular stomatitis virus Ebola vaccine in healthy adults: a randomised clinical trial. CMAJ. 2017;189(24):E819–27.CrossRefPubMedPubMedCentral
22.
go back to reference Wong G, Audet J, Fernando L, Fauster-Bovendo H, Alimonti JB, Kobinger GP, et al. Immunization with vesicular stomatitis virus vaccine expressing the Ebola glycoprotein provides sustained long-term protection in rodents. Vaccine. 2014;32(43):5722–9.CrossRefPubMed Wong G, Audet J, Fernando L, Fauster-Bovendo H, Alimonti JB, Kobinger GP, et al. Immunization with vesicular stomatitis virus vaccine expressing the Ebola glycoprotein provides sustained long-term protection in rodents. Vaccine. 2014;32(43):5722–9.CrossRefPubMed
23.
go back to reference Wong G, Qiu X, Ebihara H, Feldmann H, Kobinger GP. Characterization of a bivalent vaccine capable of inducing protection against both Ebola and cross-clade H5N1 influenza in mice. J Infect Dis. 2015;212(Suppl 2):S435–42.CrossRefPubMedPubMedCentral Wong G, Qiu X, Ebihara H, Feldmann H, Kobinger GP. Characterization of a bivalent vaccine capable of inducing protection against both Ebola and cross-clade H5N1 influenza in mice. J Infect Dis. 2015;212(Suppl 2):S435–42.CrossRefPubMedPubMedCentral
24.
go back to reference Lorenz IC, Nguyen HT, Kemelman M, Lindsay RW, Yuan M, Wright KJ, et al. The stem of vesicular stomatitis virus G can be replaced with the HIV-1 Env membrane-proximal external region without loss of G function or membrane-proximal external region antigenic properties. AIDS Res Hum Retroviruses. 2014;30(11):1130–44.CrossRefPubMedPubMedCentral Lorenz IC, Nguyen HT, Kemelman M, Lindsay RW, Yuan M, Wright KJ, et al. The stem of vesicular stomatitis virus G can be replaced with the HIV-1 Env membrane-proximal external region without loss of G function or membrane-proximal external region antigenic properties. AIDS Res Hum Retroviruses. 2014;30(11):1130–44.CrossRefPubMedPubMedCentral
26.
go back to reference Beddows S, Schulke N, Kirschner M, Barnes K, Franti M, Michael E, et al. Evaluating the immunogenicity of a disulfide-stabilized, cleaved, trimeric form of the envelope glycoprotein complex of human immunodeficiency virus type 1. J Virol. 2005;79(14):8812–27.CrossRefPubMedPubMedCentral Beddows S, Schulke N, Kirschner M, Barnes K, Franti M, Michael E, et al. Evaluating the immunogenicity of a disulfide-stabilized, cleaved, trimeric form of the envelope glycoprotein complex of human immunodeficiency virus type 1. J Virol. 2005;79(14):8812–27.CrossRefPubMedPubMedCentral
27.
go back to reference Julien JP, Sok D, Khayat R, Lee JH, Doores KJ, Walker LM, et al. Broadly neutralizing antibody PGT121 allosterically modulates CD4 binding via recognition of the HIV-1 gp120 V3 base and multiple surrounding glycans. PLoS Path. 2013;9(5):e1003342.CrossRef Julien JP, Sok D, Khayat R, Lee JH, Doores KJ, Walker LM, et al. Broadly neutralizing antibody PGT121 allosterically modulates CD4 binding via recognition of the HIV-1 gp120 V3 base and multiple surrounding glycans. PLoS Path. 2013;9(5):e1003342.CrossRef
28.
go back to reference Dosenovic P, von Boehmer L, Escolano A, Jardine J, Freund NT, Gitlin AD, et al. Immunization for HIV-1 broadly neutralizing antibodies in human Ig knockin mice. Cell. 2015;161(7):1505–15.CrossRefPubMedPubMedCentral Dosenovic P, von Boehmer L, Escolano A, Jardine J, Freund NT, Gitlin AD, et al. Immunization for HIV-1 broadly neutralizing antibodies in human Ig knockin mice. Cell. 2015;161(7):1505–15.CrossRefPubMedPubMedCentral
29.
go back to reference Sok D, Briney B, Jardine JG, Kulp DW, Menis S, Pauthner M, et al. Priming HIV-1 broadly neutralizing antibody precursors in human Ig loci transgenic mice. Science. 2016;353(6307):1557–60.CrossRefPubMed Sok D, Briney B, Jardine JG, Kulp DW, Menis S, Pauthner M, et al. Priming HIV-1 broadly neutralizing antibody precursors in human Ig loci transgenic mice. Science. 2016;353(6307):1557–60.CrossRefPubMed
30.
go back to reference Wong G, Richardson JS, Pillet S, Patel A, Qiu X, Alimonti J, et al. Immune parameters correlate with protection against ebola virus infection in rodents and nonhuman primates. Sci Transl Med. 2012;4(158):158ra146.CrossRefPubMedPubMedCentral Wong G, Richardson JS, Pillet S, Patel A, Qiu X, Alimonti J, et al. Immune parameters correlate with protection against ebola virus infection in rodents and nonhuman primates. Sci Transl Med. 2012;4(158):158ra146.CrossRefPubMedPubMedCentral
31.
go back to reference McCoy LE, van Gils MJ, Ozorowski G, Messmer T, Briney B, Voss JE, et al. Holes in the glycan shield of the native HIV envelope are a target of trimer-elicited neutralizing antibodies. Cell Rep. 2016;16(9):2327–38.CrossRefPubMedPubMedCentral McCoy LE, van Gils MJ, Ozorowski G, Messmer T, Briney B, Voss JE, et al. Holes in the glycan shield of the native HIV envelope are a target of trimer-elicited neutralizing antibodies. Cell Rep. 2016;16(9):2327–38.CrossRefPubMedPubMedCentral
32.
go back to reference Kong L, Ju B, Chen Y, He L, Ren L, Liu J, et al. Key gp120 glycans pose roadblocks to the rapid development of VRC01-class antibodies in an HIV-1-infected chinese donor. Immunity. 2016;44(4):939–50.CrossRefPubMedPubMedCentral Kong L, Ju B, Chen Y, He L, Ren L, Liu J, et al. Key gp120 glycans pose roadblocks to the rapid development of VRC01-class antibodies in an HIV-1-infected chinese donor. Immunity. 2016;44(4):939–50.CrossRefPubMedPubMedCentral
33.
go back to reference Wang H, Cohen AA, Galimidi RP, Gristick HB, Jensen GJ, Bjorkman PJ. Cryo-EM structure of a CD4-bound open HIV-1 envelope trimer reveals structural rearrangements of the gp120 V1V2 loop. PNAS. 2016;113(46):E7151–8.CrossRefPubMedPubMedCentral Wang H, Cohen AA, Galimidi RP, Gristick HB, Jensen GJ, Bjorkman PJ. Cryo-EM structure of a CD4-bound open HIV-1 envelope trimer reveals structural rearrangements of the gp120 V1V2 loop. PNAS. 2016;113(46):E7151–8.CrossRefPubMedPubMedCentral
34.
go back to reference Finzi A, Xiang SH, Pacheco B, Wang L, Haight J, Kassa A, et al. Topological layers in the HIV-1 gp120 inner domain regulate gp41 interaction and CD4-triggered conformational transitions. Mol Cell. 2010;37(5):656–67.CrossRefPubMedPubMedCentral Finzi A, Xiang SH, Pacheco B, Wang L, Haight J, Kassa A, et al. Topological layers in the HIV-1 gp120 inner domain regulate gp41 interaction and CD4-triggered conformational transitions. Mol Cell. 2010;37(5):656–67.CrossRefPubMedPubMedCentral
35.
go back to reference Ratcliff AN, Shi W, Arts EJ. HIV-1 resistance to maraviroc conferred by a CD4 binding site mutation in the envelope glycoprotein gp120. J Virol. 2013;87(2):923–34.CrossRefPubMedPubMedCentral Ratcliff AN, Shi W, Arts EJ. HIV-1 resistance to maraviroc conferred by a CD4 binding site mutation in the envelope glycoprotein gp120. J Virol. 2013;87(2):923–34.CrossRefPubMedPubMedCentral
36.
go back to reference Roche S, Bressanelli S, Rey FA, Gaudin Y. Crystal structure of the low-pH form of the vesicular stomatitis virus glycoprotein G. Science. 2006;313(5784):187–91.CrossRefPubMed Roche S, Bressanelli S, Rey FA, Gaudin Y. Crystal structure of the low-pH form of the vesicular stomatitis virus glycoprotein G. Science. 2006;313(5784):187–91.CrossRefPubMed
37.
go back to reference Kwon YD, Pancera M, Acharya P, Georgiev IS, Crooks ET, Goman J, et al. Crystal structure, conformational fixation and entry-related interactions of mature ligand-free HIV-1 Env. Nat Struct Mol Biol. 2015;22(7):522–31.CrossRefPubMedPubMedCentral Kwon YD, Pancera M, Acharya P, Georgiev IS, Crooks ET, Goman J, et al. Crystal structure, conformational fixation and entry-related interactions of mature ligand-free HIV-1 Env. Nat Struct Mol Biol. 2015;22(7):522–31.CrossRefPubMedPubMedCentral
38.
go back to reference Huang CC, Lam SN, Acharya P, Tang M, Xiang SH, Hussan SS, et al. Structures of the CCR5 N terminus and of a tyrosine-sulfated antibody with HIV-1 gp120 and CD4. Science. 2007;317(5846):1930–4.CrossRefPubMedPubMedCentral Huang CC, Lam SN, Acharya P, Tang M, Xiang SH, Hussan SS, et al. Structures of the CCR5 N terminus and of a tyrosine-sulfated antibody with HIV-1 gp120 and CD4. Science. 2007;317(5846):1930–4.CrossRefPubMedPubMedCentral
Metadata
Title
Development of an HIV vaccine using a vesicular stomatitis virus vector expressing designer HIV-1 envelope glycoproteins to enhance humoral responses
Authors
Trina Racine
Gary P. Kobinger
Eric J. Arts
Publication date
01-12-2017
Publisher
BioMed Central
Published in
AIDS Research and Therapy / Issue 1/2017
Electronic ISSN: 1742-6405
DOI
https://doi.org/10.1186/s12981-017-0179-2

Other articles of this Issue 1/2017

AIDS Research and Therapy 1/2017 Go to the issue