Venezuelan equine encephalitis virus vaccine candidate (V3526) safety, immunogenicity and efficacy in horses

Fine, David H.; Roberts, Brian; Teehee, Max; Terpening, Sara J.; Kelly, Cindy; Raetz, Janae L.; Baker, Dale C.; Powers, Ann M.; Bowen, Richard A.

doi:10.1016/j.vaccine.2006.10.030

Cited by 42 publications

(42 citation statements)

References 23 publications

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“…25 Development of V3526 was continued to the point of testing in a horse model of infection and showed promising results in terms of safety and protection. 26 A phase I clinical study was initiated and showed promising results in terms of immunogenicity. However, safety remained a concern, because fever and flu-like symptoms were associated with human use of the vaccine.…”

Section: Need For a Trivalent Weev Eeev And Veev Vaccinementioning

confidence: 99%

Current Strategic Thinking for the Development of a Trivalent Alphavirus Vaccine for Human Use

Wolfe

Heppner

Gardner

et al. 2014

The American Society of Tropical Medicine and Hygiene

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Abstract. Vaccinations against the encephalitic alphaviruses (western, eastern, and Venezuelan equine encephalitis virus) are of significant interest to biological defense, public health, and agricultural communities alike. Although vaccines licensed for veterinary applications are used in the Western Hemisphere and attenuated or inactivated viruses have been used under Investigational New Drug status to protect at-risk personnel, there are currently no licensed vaccines for use in humans. Here, we will discuss the need for a trivalent vaccine that can protect humans against all three viruses, recent progress to such a vaccine, and a strategy to continue development to Food and Drug Administration licensure.

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Section: Need For a Trivalent Weev Eeev And Veev Vaccinementioning

confidence: 99%

Current Strategic Thinking for the Development of a Trivalent Alphavirus Vaccine for Human Use

Wolfe

Heppner

Gardner

et al. 2014

The American Society of Tropical Medicine and Hygiene

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“…V3526 is attenuated and induces a robust protective antibody response against VEEV TrD in rodents, equines, and nonhuman primates (5,9,(14)(15)(16)37). V3526 also elicits protection in animals against challenge by other VEEV subtypes (9,15,37). During the characterization of the immune response elicited by V3526 in mice, a collection of monoclonal antibodies (MAbs) was isolated that preferentially bound V3526 virions compared to VEEV TrD.…”

mentioning

confidence: 99%

“…The virus encoded by this clone contains a 12-nucleotide deletion of the sequence encoding the furin cleavage site, as well as a Phe-to-Ser change at position 253 of the E1 glycoprotein (8). V3526 is attenuated and induces a robust protective antibody response against VEEV TrD in rodents, equines, and nonhuman primates (5,9,(14)(15)(16)37). V3526 also elicits protection in animals against challenge by other VEEV subtypes (9,15,37).…”

mentioning

confidence: 99%

Antibody to the E3 Glycoprotein Protects Mice against Lethal Venezuelan Equine Encephalitis Virus Infection

Parker

Buckley²,

Melanson

et al. 2010

J Virol

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Six monoclonal antibodies were isolated that exhibited specificity for a furin cleavage site deletion mutant (V3526) of Venezuelan equine encephalitis virus (VEEV). These antibodies comprise a single competition group and bound the E3 glycoprotein of VEEV subtype I viruses but failed to bind the E3 glycoprotein of other alphaviruses. These antibodies neutralized V3526 virus infectivity but did not neutralize the parental strain of Trinidad donkey (TrD) VEEV. However, the E3-specific antibodies did inhibit the production of virus from VEEV TrD-infected cells. In addition, passive immunization of mice demonstrated that antibody to the E3 glycoprotein provided protection against lethal VEEV TrD challenge. This is the first recognition of a protective epitope in the E3 glycoprotein. Furthermore, these results indicate that E3 plays a critical role late in the morphogenesis of progeny virus after E3 appears on the surfaces of infected cells.Viruses in the Alphavirus genus of the family Togaviridae are composed of an icosahedral nucleocapsid surrounded by a lipid envelope studded with a distinctive lattice of glycoprotein spikes. The structural proteins of alphaviruses arise through co-and posttranslational processing of a polyprotein encoded by a single 26S mRNA (22,27) in which the order of the gene products is NH 2 -capsid-PE2-6K-E1-COOH. The capsid (C) protein cleaves itself from the nascent polypeptide soon after emergence from the ribosome. The PE2 glycoprotein is a precursor containing the E3 glycoprotein fused to the amino terminus of the E2 envelope glycoprotein. The PE2 glycoprotein is followed by 6K, a small membrane-associated protein, and E1, the second polypeptide component of glycoprotein spikes. Trimerized heterodimers of the E1 and E2 viral glycoproteins form the surface spikes and contain determinants of viral tropism and virulence (1).The E3 glycoprotein acts as a signal for transport of PE2 across the membranes of the rough endoplasmic reticulum (22) and may promote the formation and intracellular transport of E1-PE2 heterodimers (12,23,46) to the cell surface. The E2 glycoprotein promotes specificity of virus binding to the host cell surface and is a target of protective antibodies (7,(18)(19)(20)39). The E1 glycoprotein mediates fusion of the virion envelope with the membranes of acidified endosomes, allowing release of the nucleocapsid into the cytoplasm and the onset of viral replication (21,40,43). Antibodies to the E1 glycoprotein do not typically neutralize virus infectivity in vitro but can protect against lethal challenge in animals (41, 42). During transport to the cell surface, PE2 undergoes a maturational cleavage event by a furin-like protease to produce E2 and E3. The E3 glycoprotein may be subsequently released into the extracellular space (26, 49) or incorporated into the virion (6, 13). At the plasma membrane, trimerized E1-E2 heterodimers are incorporated into the budding virus particle.Mutations that block cleavage of PE2 of Venezuelan equine encephalitis virus (VEEV) are lethal ...

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“…The Venezuelan equine encephalitis virus (VEEV) belongs to the VEE complex, which consists of six subtypes which have been identified in North, Central and South America (Fig. 3.1e) (Fine et al 2007;Weaver et al 1992). The first isolation of VEEV was in 1938 from the brain of a Venezuelan animal (Beck and Wyckhoff 1938).…”

Section: Togaviridaementioning

confidence: 99%

Bats as Potential Reservoir Hosts for Vector-Borne Diseases

Melaun

Werblow

Busch

et al. 2013

Bats (Chiroptera) as Vectors of Diseases and Parasites

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Venezuelan equine encephalitis virus vaccine candidate (V3526) safety, immunogenicity and efficacy in horses

Cited by 42 publications

References 23 publications

Current Strategic Thinking for the Development of a Trivalent Alphavirus Vaccine for Human Use

Current Strategic Thinking for the Development of a Trivalent Alphavirus Vaccine for Human Use

Antibody to the E3 Glycoprotein Protects Mice against Lethal Venezuelan Equine Encephalitis Virus Infection

Bats as Potential Reservoir Hosts for Vector-Borne Diseases

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