Mucosal and systemic adjuvant activity of alphavirus replicon particles
| Autor: | Herman F. Staats, Joseph M. Thompson, Nancy L. Davis, Robert E. Johnston, Alan C. Whitmore, Jennifer L. Konopka, Martha Collier, Erin M. B. Richmond |
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| Rok vydání: | 2006 |
| Předmět: |
Cholera Toxin
Ovalbumin medicine.medical_treatment Alphavirus medicine.disease_cause Immunoglobulin G Encephalitis Virus Venezuelan Equine Mice Adjuvants Immunologic Antigen Immunity medicine Animals Replicon Immunity Mucosal Mice Inbred BALB C Multidisciplinary biology Antigen processing Biological Sciences biochemical phenomena metabolism and nutrition biology.organism_classification Virology Immunoglobulin A Oligodeoxyribonucleotides Venezuelan equine encephalitis virus Immunology biology.protein Female Immunization Adjuvant |
| Zdroj: | Proceedings of the National Academy of Sciences. 103:3722-3727 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0600287103 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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