Recombinant vesicular stomatitis virus as an HIV-1 vaccine vector

ABSTRACT The demonstrated clinical efficacy of a recombinant vesicular stomatitis virus (rVSV) vaccine vector has stimulated the investigation of additional serologically distinct Vesiculovirus vectors as therapeutic and/or prophylactic vaccine vectors to combat emerging viral diseases. Among these viral threats are the encephalitic alphaviruses Venezuelan equine encephalitis virus (VEEV) and Eastern equine encephalitis virus (EEEV), which have demonstrated potential for natural disease outbreaks, yet no licensed vaccines are available in the event of an epidemic. Here we report the rescue of recombinant Isfahan virus (rISFV) from genomic cDNA as a potential new vaccine vector platform. The rISFV genome was modified to attenuate virulence and express the VEEV and EEEV E2/E1 surface glycoproteins as vaccine antigens. A single dose of the rISFV vaccine vectors elicited neutralizing antibody responses and protected mice from lethal VEEV and EEEV challenges at 1 month postvaccination as well as lethal VEEV challenge at 8 months postvaccination. A mixture of rISFV vectors expressing the VEEV and EEEV E2/E1 glycoproteins also provided durable, single-dose protection from lethal VEEV and EEEV challenges, demonstrating the potential for a multivalent vaccine formulation. These findings were paralleled in studies with an attenuated form of rVSV expressing the VEEV E2/E1 glycoproteins. Both the rVSV and rISFV vectors were attenuated by using an approach that has demonstrated safety in human trials of an rVSV/HIV-1 vaccine. Vaccines based on either of these vaccine vector platforms may present a safe and effective approach to prevent alphavirus-induced disease in humans. IMPORTANCE This work introduces rISFV as a novel vaccine vector platform that is serologically distinct and phylogenetically distant from VSV. The rISFV vector has been attenuated by an approach used for an rVSV vector that has demonstrated safety in clinical studies. The vaccine potential of the rISFV vector was investigated in a well-established alphavirus disease model. The findings indicate the feasibility of producing a safe, efficacious, multivalent vaccine against the encephalitic alphaviruses VEEV and EEEV, both of which can cause fatal disease. This work also demonstrates the efficacy of an attenuated rVSV vector that has already demonstrated safety and immunogenicity in multiple HIV-1 phase I clinical studies. The absence of serological cross-reactivity between rVSV and rISFV and their phylogenetic divergence within the Vesiculovirus genus indicate potential for two stand-alone vaccine vector platforms that could be used to target multiple bacterial and/or viral agents in successive immunization campaigns or as heterologous prime-boost agents.

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Induction of Tier 1 HIV Neutralizing Antibodies by Envelope Trimers Incorporated into a Replication Competent Vesicular Stomatitis Virus Vector

Viruses ◽

10.3390/v11020159 ◽

2019 ◽

Vol 11 (2) ◽

pp. 159 ◽

Cited By ~ 8

Author(s):

C. Bresk ◽

Tamara Hofer ◽

Sarah Wilmschen ◽

Marina Krismer ◽

Anja Beierfuß ◽

...

Keyword(s):

Vesicular Stomatitis Virus ◽

Neutralizing Antibodies ◽

Vaccine Vector ◽

Furin Cleavage ◽

Vector Vaccine ◽

Furin Cleavage Site ◽

Viral Vaccine ◽

Antibody Titers ◽

Vesicular Stomatitis ◽

Hiv 1

A chimeric vesicular stomatitis virus with the glycoprotein of the lymphocytic choriomeningitis virus, VSV-GP, is a potent viral vaccine vector that overcomes several of the limitations of wild-type VSV. Here, we evaluated the potential of VSV-GP as an HIV vaccine vector. We introduced genes for different variants of the HIV-1 envelope protein Env, i.e., secreted or membrane-anchored, intact or mutated furin cleavage site or different C-termini, into the genome of VSV-GP. We found that the addition of the Env antigen did not attenuate VSV-GP replication. All HIV-1 Env variants were expressed in VSV-GP infected cells and some were incorporated very efficiently into VSV-GP particles. Crucial epitopes for binding of broadly neutralizing antibodies against HIV-1 such as MPER (membrane-proximal external region), CD4 binding site, V1V2 and V3 loop were present on the surface of VSV-GP-Env particles. Binding of quaternary antibodies indicated a trimeric structure of VSV-GP incorporated Env. We detected high HIV-1 antibody titers in mice and showed that vectors expressing membrane-anchored Env elicited higher antibody titers than vectors that secreted Envs. In rabbits, Tier 1A HIV-1 neutralizing antibodies were detectable after prime immunization and titers further increased after boosting with a second immunization. Taken together, VSV-GP-Env is a promising vector vaccine against HIV-1 infection since this vector permits incorporation of native monomeric and/or trimeric HIV-1 Env into a viral membrane.

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In vivo biodistribution of a highly attenuated recombinant vesicular stomatitis virus expressing HIV-1 Gag following intramuscular, intranasal, or intravenous inoculation

Vaccine ◽

10.1016/j.vaccine.2009.03.006 ◽

2009 ◽

Vol 27 (22) ◽

pp. 2930-2939 ◽

Cited By ~ 23

Author(s):

J. Erik Johnson ◽

John W. Coleman ◽

Narender K. Kalyan ◽

Priscilla Calderon ◽

Kevin J. Wright ◽

...

Keyword(s):

Vesicular Stomatitis Virus ◽

In Vivo Biodistribution ◽

Vesicular Stomatitis ◽

Intravenous Inoculation ◽

Hiv 1

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An optimized vaccine vector based on recombinant vesicular stomatitis virus gives high-level, long-term protection against Yersinia pestis challenge

Vaccine ◽

10.1016/j.vaccine.2006.08.010 ◽

2007 ◽

Vol 25 (4) ◽

pp. 741-750 ◽

Cited By ~ 22

Author(s):

Amy Palin ◽

Anasuya Chattopadhyay ◽

Steven Park ◽

Guillaume Delmas ◽

Rema Suresh ◽

...

Keyword(s):

Yersinia Pestis ◽

Vesicular Stomatitis Virus ◽

Vaccine Vector ◽

Vesicular Stomatitis ◽

High Level

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Type III Interferon Attenuates a Vesicular Stomatitis Virus-Based Vaccine Vector

Journal of Virology ◽

10.1128/jvi.01910-14 ◽

2014 ◽

Vol 88 (18) ◽

pp. 10909-10917 ◽

Cited By ~ 3

Author(s):

R. C. Guayasamin ◽

T. D. Reynolds ◽

X. Wei ◽

M. Fujiwara ◽

M. D. Robek

Keyword(s):

Vesicular Stomatitis Virus ◽

Vaccine Vector ◽

Type Iii ◽

Vesicular Stomatitis ◽

Type Iii Interferon

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In vitro inhibition of vesicular stomatitis virus replication by purified porcine Mx1 protein fused to HIV-1 Tat protein transduction domain (PTD)

Antiviral Research ◽

10.1016/j.antiviral.2013.05.009 ◽

2013 ◽

Vol 99 (2) ◽

pp. 149-157 ◽

Cited By ~ 15

Author(s):

Xiao-min Zhang ◽

Dan-Ni He ◽

Bin Zhou ◽

Ran Pang ◽

Ke Liu ◽

...

Keyword(s):

Vesicular Stomatitis Virus ◽

Virus Replication ◽

Protein Transduction ◽

Protein Transduction Domain ◽

Tat Protein ◽

Vesicular Stomatitis ◽

In Vitro Inhibition ◽

Hiv 1 ◽

Tat Protein Transduction Domain

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A recombinant vesicular stomatitis virus encoding CCR5-tropic HIV-1 receptors targets HIV-1-infected cells and controls HIV-1 infection

Microbes and Infection ◽

10.1016/j.micinf.2016.12.004 ◽

2017 ◽

Vol 19 (4-5) ◽

pp. 277-287 ◽

Cited By ~ 2

Author(s):

Kazu Okuma ◽

Koji Fukagawa ◽

Takuya Kohma ◽

Youichi Takahama ◽

Yukio Hamaguchi ◽

...

Keyword(s):

Vesicular Stomatitis Virus ◽

Infected Cells ◽

Vesicular Stomatitis ◽

Hiv 1

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The Immune Response to a Vesicular Stomatitis Virus Vaccine Vector Is Independent of Particulate Antigen Secretion and Protein Turnover Rate

Journal of Virology ◽

10.1128/jvi.05991-11 ◽

2012 ◽

Vol 86 (8) ◽

pp. 4253-4261 ◽

Cited By ~ 9

Author(s):

Melissa A. Cobleigh ◽

Clinton Bradfield ◽

Yuanjie Liu ◽

Anand Mehta ◽

Michael D. Robek

Keyword(s):

Immune Response ◽

Vesicular Stomatitis Virus ◽

Virus Vaccine ◽

Protein Turnover ◽

Turnover Rate ◽

Vaccine Vector ◽

Particulate Antigen ◽

Vesicular Stomatitis

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Expression of HIV-1 gag and env genes using the vesicular stomatitis virus vector system

Western Undergraduate Research Journal Health and Natural Sciences ◽

10.5206/wurjhns.2014-15.13 ◽

2014 ◽

Vol 5 (1) ◽

Author(s):

Justine M Baek

Keyword(s):

Vesicular Stomatitis Virus ◽

Recombinant Virus ◽

Viral Vector ◽

Genetically Modified ◽

Hiv Vaccine ◽

Virus Vector ◽

Vector System ◽

Temperature Sensitive ◽

Vesicular Stomatitis ◽

Hiv 1

Traditional vaccine methods have long been employed to control widespread infectious diseases, but so far, all commercially available vaccine strategies have been inadequate in efforts to develop an effective therapeutic HIV vaccine. However, recent advancements in immunological research have led to the generation of novel vaccine strategies, one of which is the recombinant virus vaccine, a method of particular interest that has shown promise in the clearance of HIV infection within HIV-positive patients who have retained immunocompetence. This study examined the stability of expression of HIV-1 genes, gag and env, through a recombinant virus vector, a recombinant vesicular stomatitis virus (VSV), a temperature-sensitive mutant genetically modified to contain the select HIV-1 genes (VSVInd(GML)HIV-1gag-env). For SDS-PAGE, cells infected with VSVInd(GML) temperature-sensitive mutants were incubated at 31 °C and 37 °C, the permissible and semi-permissible growth conditions respectively. Western blot analyses were used to quantitate levels of protein expression of full VSV proteins, Gag, and Env using a primary rabbit antibody of anti-VSV anti-serum and a secondary anti-IgG from rabbit, a primary antibody of anti-p24 anti-serum and a secondary anti-IgG from rabbit, and a primary goat antibody, anti-gp120, and a secondary anti-IgG from goat, respectively. Results indicated that the VSVInd(GML) vector system allowed for high levels of expression of HIV-1 gag and env genes. It is known that the expression of these genes induce the production of major neutralizing antibodies and the stimulation of cytotoxic T lymphocytes, therefore this finding reveals the potential to use a genetically modified recombinant VSV as a universal vector for the development of recombinant virus vaccines. Specifically, the VSVInd(GML) mutant vector is thus an attractive candidate for the viral vector of a therapeutic HIV vaccine system.

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Vesicular Stomatitis Virus: From Agricultural Pathogen to Vaccine Vector

Pathogens ◽

10.3390/pathogens10091092 ◽

2021 ◽

Vol 10 (9) ◽

pp. 1092

Author(s):

Guodong Liu ◽

Wenguang Cao ◽

Abdjeleel Salawudeen ◽

Wenjun Zhu ◽

Karla Emeterio ◽

...

Keyword(s):

Vesicular Stomatitis Virus ◽

Reverse Genetics ◽

Ebola Virus ◽

Rna Virus ◽

Research Tool ◽

Vaccine Vector ◽

The Family ◽

Vesicular Stomatitis ◽

Negative Sense ◽

Family Rhabdoviridae

Vesicular stomatitis virus (VSV), which belongs to the Vesiculovirus genus of the family Rhabdoviridae, is a well studied livestock pathogen and prototypic non-segmented, negative-sense RNA virus. Although VSV is responsible for causing economically significant outbreaks of vesicular stomatitis in cattle, horses, and swine, the virus also represents a valuable research tool for molecular biologists and virologists. Indeed, the establishment of a reverse genetics system for the recovery of infectious VSV from cDNA transformed the utility of this virus and paved the way for its use as a vaccine vector. A highly effective VSV-based vaccine against Ebola virus recently received clinical approval, and many other VSV-based vaccines have been developed, particularly for high-consequence viruses. This review seeks to provide a holistic but concise overview of VSV, covering the virus’s ascension from perennial agricultural scourge to promising medical countermeasure, with a particular focus on vaccines.

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