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Vaccine2006; 25(10); 1868-1876; doi: 10.1016/j.vaccine.2006.10.030

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

Abstract: A new vaccine, V3526, is a live-attenuated virus derived by site-directed mutagenesis from a virulent clone of the Venezuelan equine encephalitis virus (VEEV) IA/B Trinidad donkey (TrD) strain, intended for human use in protection against Venezuelan equine encephalitis (VEE). Two studies were conducted in horses to evaluate the safety, immunogenicity, ability to boost and protective efficacy of V3526 against challenges of TrD and VEEV IE 64A99. Horses were vaccinated subcutaneously (SC) with 10(7), 10(5), 10(3) or 10(2) plaque-forming units (pfu) of V3526. Control horses were sham immunized. In the first study, challenge viruses (TrD or 64A99) were administered SC 28 days post-vaccination (PV). No viremia and only mild fluctuation in white blood cell counts were observed PV. None of the V3526 vaccinated horses showed clinical signs of disease or pathology of VEE post-challenge (PC). In contrast, control horses challenged SC with 10(4)pfu TrD became viremic and showed classical signs of VEE beginning on Day 3 PC, including elevated body temperature, anorexia, leukopenia and malaise. Moderate to severe encephalitis was found in three of five control horses challenged with TrD. Control horses challenged with 64A99 failed to develop detectable viremia, but did exhibit a brief febrile episode at 1-3 days PC. None of the 10 immunized horses challenged with 64A99 became pyrexic. Twenty four of 25 horses immunized with V3526 in the first study developed serum neutralizing antibody to TrD and 64A99 within 14 days PV. Vaccinations with V3526, at doses as low as 10(2)pfu, were safe and efficacious in protecting horses against a virulent TrD virus challenge. The second study supported that repeat dosing resulted in an increase in serum neutralizing antibody to TrD.
Publication Date: 2006-10-27 PubMed ID: 17240002DOI: 10.1016/j.vaccine.2006.10.030Google Scholar: Lookup
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  • Clinical Trial
  • Journal Article
  • Research Support
  • U.S. Gov't
  • Non-P.H.S.

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research paper describes the development of a new vaccine against the Venezuelan equine encephalitis virus (VEEV), termed V3526. This vaccine, designed for humans, was evaluated for its safety, efficacy, and immune response in horses. The findings indicated that the vaccine is safe and effective even at low doses, and repeat dosing led to an increased immune response.

Overview of the Study

  • The research paper discusses two studies carried out to evaluate the safety, immune response, and efficacy of a new vaccine, V3526, that aims to provide protection against Venezuelan Equine Encephalitis (VEE). This new vaccine is a live-attenuated virus derived by site-directed mutagenesis from a virulent clone of the VEEV.
  • The studies were conducted on horses, which were vaccinated subcutaneously with varying doses of V3526. Another group of control horses were sham immunized, meaning they were given a fake or placebo vaccine. Following vaccination, the horses were challenged with either a TrD or 64A99 strain of VEEV.

Study Results

  • Post-vaccination results showed no viremia, or presence of viruses in the blood, and only slight fluctuations in white blood cell counts. Importantly, no clinical signs of VEE disease were observed in the vaccinated horses post-challenge.
  • In stark contrast, control horses showed signs of VEE disease, including fever, loss of appetite, leukopenia (low white blood cell count), and general discomfort. Among the control group, those challenged with the TrD strain even developed moderate to severe encephalitis or brain inflammation. While those challenged with the 64A99 strain didn’t develop detectable viremia, they exhibited brief fever episodes.
  • The study found that nearly all the horses vaccinated with V3526 developed serum neutralizing antibodies against both the TrD and 64A99 strains within 14 days post-vaccination. These antibodies are essential components of the immune system that neutralize viruses, thereby suggesting a successful immune response.
  • The low dose vaccinations of V3526, as low as 10(2) plaque-forming units, were found to be safe and efficacious in protecting horses against a virulent TrD virus challenge.

Additional Findings and Conclusions

  • The second phase of the study corroborated the findings of the first, additionally indicating that repeat dosing of the vaccine led to an increase in serum neutralizing antibody to TrD. This suggests that the vaccine’s effectiveness could potentially be boosted through additional doses.
  • Taken together, the research demonstrates the potential effectiveness of the V3526 vaccine in combating VEEV. However, it’s worth noting that this study was carried out on horses, hence further research will be needed to test its safety and efficacy in humans.

Cite This Article

APA
Fine DL, Roberts BA, Teehee ML, Terpening SJ, Kelly CL, Raetz JL, Baker DC, Powers AM, Bowen RA. (2006). Venezuelan equine encephalitis virus vaccine candidate (V3526) safety, immunogenicity and efficacy in horses. Vaccine, 25(10), 1868-1876. https://doi.org/10.1016/j.vaccine.2006.10.030

Publication

ISSN: 0264-410X
NlmUniqueID: 8406899
Country: Netherlands
Language: English
Volume: 25
Issue: 10
Pages: 1868-1876

Researcher Affiliations

Fine, Donald L
  • DynPort Vaccine Company LLC (DVC), A CSC Company, 64 Thomas Johnson Drive, Frederick, MD 21702, USA. dfine@csc.com
Roberts, Brian A
    Teehee, Max L
      Terpening, Sara J
        Kelly, Cindy L H
          Raetz, Janae L
            Baker, Dale C
              Powers, Ann M
                Bowen, Richard A

                  MeSH Terms

                  • Animals
                  • Encephalitis Virus, Venezuelan Equine / immunology
                  • Encephalitis Virus, Venezuelan Equine / isolation & purification
                  • Encephalomyelitis, Venezuelan Equine / pathology
                  • Encephalomyelitis, Venezuelan Equine / physiopathology
                  • Encephalomyelitis, Venezuelan Equine / prevention & control
                  • Female
                  • Histocytochemistry
                  • Horse Diseases / prevention & control
                  • Horses
                  • Injections, Subcutaneous
                  • Kidney / pathology
                  • Leukocyte Count
                  • Liver / pathology
                  • Lung / pathology
                  • Lymph Nodes / pathology
                  • Male
                  • Myocardium / pathology
                  • Pancreas / pathology
                  • Spleen / pathology
                  • Telencephalon / pathology
                  • Vaccines, Attenuated / adverse effects
                  • Vaccines, Attenuated / immunology
                  • Viral Plaque Assay
                  • Viral Vaccines / adverse effects
                  • Viral Vaccines / immunology
                  • Viremia / prevention & control

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