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Home / Equine Research Bank / Proc Natl Acad Sci U S A / Mucosal and systemic adjuvant activity of alphavirus replico...
Proceedings of the National Academy of Sciences of the United States of America2006; 103(10); 3722-3727; doi: 10.1073/pnas.0600287103

Mucosal and systemic adjuvant activity of alphavirus replicon particles.

Abstract: Vaccination represents the most effective control measure in the fight against infectious diseases. Local mucosal immune responses are critical for protection from, and resolution of, infection by numerous mucosal pathogens. Antigen processing across mucosal surfaces is the natural route by which mucosal immunity is generated, as peripheral antigen delivery typically fails to induce mucosal immune responses. However, we demonstrate in this article that mucosal immune responses are evident at multiple mucosal surfaces after parenteral delivery of Venezuelan equine encephalitis virus replicon particles (VRP). Moreover, coinoculation of null VRP (not expressing any transgene) with inactivated influenza virions, or ovalbumin, resulted in a significant increase in antigen-specific systemic IgG and fecal IgA antibodies, compared with antigen alone. Pretreatment of VRP with UV light largely abrogated this adjuvant effect. These results demonstrate that alphavirus replicon particles possess intrinsic systemic and mucosal adjuvant activity and suggest that VRP RNA replication is the trigger for this activity. We feel that these observations and the continued experimentation they stimulate will ultimately define the specific components of an alternative pathway for the induction of mucosal immunity, and if the activity is evident in humans, will enable new possibilities for safe and inexpensive subunit and inactivated vaccines.
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Publication Date: 2006-02-27 PubMed ID: 16505353PubMed Central: PMC1383499DOI: 10.1073/pnas.0600287103Google Scholar: Lookup
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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 abstract discusses a study showing that Venezuelan equine encephalitis virus replicon particles (VRP) have intrinsic systemic and mucosal adjuvant activity, which can enhance the body’s immune response after vaccination. This process may pave the way for safe, inexpensive vaccines.

Explanation of the Research

  • The featured investigation revolves around the capacity of Venezuelan equine encephalitis virus replicon particles to act as adjuvants, substances that enhance the body’s immune response to a vaccine. This capacity is demonstrated across multiple mucosal surfaces even after peripheral delivery. Mucosal surfaces refer to the moist, inner lining of some organs and body cavities, making them a crucial part of the immune response towards many pathogens.
  • The research was conducted by co-inoculating (simultaneously injecting) null VRP (VRP not expressing any transgene) with inactivated influenza virions or ovalbumin. The result was a significant increase in the production of IgG (an indicator of a systemic immune response) and fecal IgA antibodies (which suggest a mucosal immune response), compared to using the antigens alone.
  • The VRP’s adjuvant effect, however, was largely negated when the VRP was pretreated with UV light. This seemed to imply that the VRP’s RNA replication process was the main causative factor behind the adjuvant activity.

Implications of the Research

  • This research is significant in the field of infectious diseases and immunology as it presents an alternative pathway for inducing mucosal immunity. While additional research is needed, this observation can redefine the understanding of the human immune response and the process of vaccine development.
  • The research suggests that VRP’s inherently possess their own systemic and mucosal adjuvant activity. If the same activity is evident in humans, it could open up opportunities for creating new subunit and inactivated vaccines which can be cheaper, less risky, and more effective against mucosal pathogens.

Cite This Article

APA
Thompson JM, Whitmore AC, Konopka JL, Collier ML, Richmond EM, Davis NL, Staats HF, Johnston RE. (2006). Mucosal and systemic adjuvant activity of alphavirus replicon particles. Proc Natl Acad Sci U S A, 103(10), 3722-3727. https://doi.org/10.1073/pnas.0600287103

Publication

Proceedings of the National Academy of Sciences of the United States of America
ISSN: 0027-8424
NlmUniqueID: 7505876
Country: United States
Language: English
Volume: 103
Issue: 10
Pages: 3722-3727

Researcher Affiliations

Thompson, Joseph M
  • Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599, USA.
Whitmore, Alan C
    Konopka, Jennifer L
      Collier, Martha L
        Richmond, Erin M B
          Davis, Nancy L
            Staats, Herman F
              Johnston, Robert E

                MeSH Terms

                • Adjuvants, Immunologic / administration & dosage
                • Animals
                • Cholera Toxin / administration & dosage
                • Cholera Toxin / immunology
                • Encephalitis Virus, Venezuelan Equine / immunology
                • Female
                • Immunity, Mucosal
                • Immunization
                • Immunoglobulin A / biosynthesis
                • Immunoglobulin G / biosynthesis
                • Mice
                • Mice, Inbred BALB C
                • Oligodeoxyribonucleotides / administration & dosage
                • Oligodeoxyribonucleotides / immunology
                • Ovalbumin / administration & dosage
                • Ovalbumin / immunology
                • Replicon / immunology

                Grant Funding

                • P01 AI046023 / NIAID NIH HHS
                • R01 AI051990 / NIAID NIH HHS
                • P01-AI46023 / NIAID NIH HHS
                • R01-AI51990 / NIAID NIH HHS

                Conflict of Interest Statement

                Conflict of interest statement: J.M.T. and R.E.J. are listed inventors on a patent application related to the subject matter of this article. R.E.J. is the unpaid Executive Director of Global Vaccines, Inc., a not-for-profit company that holds a license to the technology described in the article.

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