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Journal of virology2014; 88(20); 12077-12086; doi: 10.1128/JVI.01406-14

Combined alphavirus replicon particle vaccine induces durable and cross-protective immune responses against equine encephalitis viruses.

Abstract: Alphavirus replicons were evaluated as potential vaccine candidates for Venezuelan equine encephalitis virus (VEEV), western equine encephalitis virus (WEEV), or eastern equine encephalitis virus (EEEV) when given individually or in combination (V/W/E) to mice or cynomolgus macaques. Individual replicon vaccines or the combination V/W/E replicon vaccine elicited strong neutralizing antibodies in mice to their respective alphavirus. Protection from either subcutaneous or aerosol challenge with VEEV, WEEV, or EEEV was demonstrated out to 12 months after vaccination in mice. Individual replicon vaccines or the combination V/W/E replicon vaccine elicited strong neutralizing antibodies in macaques and demonstrated good protection against aerosol challenge with an epizootic VEEV-IAB virus, Trinidad donkey. Similarly, the EEEV replicon and V/W/E combination vaccine elicited neutralizing antibodies against EEEV and protected against aerosol exposure to a North American variety of EEEV. Both the WEEV replicon and combination V/W/E vaccination, however, elicited poor neutralizing antibodies to WEEV in macaques, and the protection conferred was not as strong. These results demonstrate that a combination V/W/E vaccine is possible for protection against aerosol challenge and that cross-interference between the vaccines is minimal. Importance: Three related viruses belonging to the genus Alphavirus cause severe encephalitis in humans: Venezuelan equine encephalitis virus (VEEV), western equine encephalitis virus (WEEV), and eastern equine encephalitis virus (EEEV). Normally transmitted by mosquitoes, these viruses can cause disease when inhaled, so there is concern that these viruses could be used as biological weapons. Prior reports have suggested that vaccines for these three viruses might interfere with one another. We have developed a combined vaccine for Venezuelan equine encephalitis, western equine encephalitis, and eastern equine encephalitis expressing the surface proteins of all three viruses. In this report we demonstrate in both mice and macaques that this combined vaccine is safe, generates a strong immune response, and protects against aerosol challenge with the viruses that cause Venezuelan equine encephalitis, western equine encephalitis, and eastern equine encephalitis.
Copyright © 2014, American Society for Microbiology. All Rights Reserved.
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Publication Date: 2014-08-13 PubMed ID: 25122801PubMed Central: PMC4178741DOI: 10.1128/JVI.01406-14Google Scholar: Lookup
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  • Extramural
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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 article investigates the potency of alphavirus replicons in developing a vaccine against equine encephalitis viruses. The study reported positive results when the vaccine was used on mice and macaques to protect against Venezuelan, western, and eastern equine encephalitis viruses.

Research Methodology

  • The research evaluated the potential of alphavirus replicons in generating vaccine candidates for three different types of equine encephalitis viruses—VEEV, WEEV, and EEEV.
  • The vaccines were given either individually or in combination (V/W/E) to both mice and cynomolgus macaques.

Research Findings in Mice

  • Both the individual and combined replicon vaccines triggered strong neutralizing antibodies in mice against their corresponding alphavirus.
  • The immunity provided by these vaccines was enduring, as protection from either subcutaneous or aerosol challenge with VEEV, WEEV, or EEEV lasted up to 12 months post-vaccination.

Research Findings in Macaques

  • Similar to the findings in mice, both individual and combined V/W/E replicon vaccines invoked strong neutralizing antibodies in macaques.
  • The vaccines displayed a good level of protection against aerosol challenge with VEEV-IAB virus of Trinidad donkey origin.
  • The EEEV replicon and V/W/E combined vaccine also induced neutralizing antibodies against EEEV and ensured protection from aerosol exposure to a North American variety of EEEV.
  • The combined V/W/E vaccination and the WEEV replicon, however, elicited poor neutralizing antibodies to WEEV in macaques, and the level of protection rendered was not as strong as seen in the other viruses.

Conclusion & Importance

  • The success of the combination V/W/E vaccine in offering protection against aerosol challenges, along with the minimal cross-interference between the vaccines, supports its potential use for human immunization.
  • The research is significant as it targets three related viruses—VEEV, WEEV, EEEV—all of which belong to the Alphavirus genus and cause grave encephalitis in humans. They are naturally transmitted through mosquitoes and can cause disease when inhaled, raising concerns over their potential use as bio-weapons.
  • While previous studies speculated that vaccines for these three viruses might interfere with one another, this research presents a combined vaccine that is safe, stimulates a strong immune response, and secures protection against the viruses causing Venezuelan, western, and eastern equine encephalitis.

Cite This Article

APA
Reed DS, Glass PJ, Bakken RR, Barth JF, Lind CM, da Silva L, Hart MK, Rayner J, Alterson K, Custer M, Dudek J, Owens G, Kamrud KI, Parker MD, Smith J. (2014). Combined alphavirus replicon particle vaccine induces durable and cross-protective immune responses against equine encephalitis viruses. J Virol, 88(20), 12077-12086. https://doi.org/10.1128/JVI.01406-14

Publication

Journal of virology
ISSN: 1098-5514
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 88
Issue: 20
Pages: 12077-12086

Researcher Affiliations

Reed, Douglas S
  • Center for Aerobiological Sciences, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA dsreed@pitt.edu.
Glass, Pamela J
  • Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
Bakken, Russell R
  • Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
Barth, James F
  • Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
Lind, Cathleen M
  • Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
da Silva, Luis
  • Center for Aerobiological Sciences, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
Hart, Mary Kate
  • Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
Rayner, Jonathan
  • AlphaVax, Inc., Research Triangle Park, North Carolina, USA.
Alterson, Kim
  • AlphaVax, Inc., Research Triangle Park, North Carolina, USA.
Custer, Max
  • AlphaVax, Inc., Research Triangle Park, North Carolina, USA.
Dudek, Jeanne
  • AlphaVax, Inc., Research Triangle Park, North Carolina, USA.
Owens, Gary
  • AlphaVax, Inc., Research Triangle Park, North Carolina, USA.
Kamrud, Kurt I
  • AlphaVax, Inc., Research Triangle Park, North Carolina, USA.
Parker, Michael D
  • Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
Smith, Jonathan
  • AlphaVax, Inc., Research Triangle Park, North Carolina, USA.

MeSH Terms

  • Alphavirus / classification
  • Alphavirus / immunology
  • Animals
  • Antibodies, Neutralizing / immunology
  • Blotting, Western
  • Chlorocebus aethiops
  • Cricetinae
  • Encephalitis Virus, Eastern Equine / classification
  • Encephalitis Virus, Eastern Equine / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fluorescent Antibody Technique
  • Macaca fascicularis
  • Male
  • Mice
  • Replicon
  • Vero Cells
  • Viral Vaccines / immunology

Grant Funding

  • U01 A|056438-04 / PHS HHS

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