T-cell-mediated protective efficacy of a systemic vaccine approach in cynomolgus monkeys after SIV mucosal challenge
| Autor: | Roberto Belli, Silvia Baroncelli, Claudia Rovetto, Leonardo Sernicola, Stefania Catone, Maria Grazia Mancini, Massimo Ciccozzi, Zahra Fagrouch, Fausto Titti, Stefania Farcomeni, Antonella Comini, Donatella R.M. Negri, Stephen Norley, Jonathan L. Heeney, Maria Teresa Maggiorella, Peter Liljeström, Federica Crostarosa, Zuleika Michelini |
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| Předmět: |
Male
viruses T-Lymphocytes Simian Acquired Immunodeficiency Syndrome Enzyme-Linked Immunosorbent Assay Vaccinia virus Semliki Forest virus Antibodies Viral Virus Viral vector chemistry.chemical_compound Interferon-gamma Interferon Neutralization Tests medicine Vaccines DNA Animals Antigens Viral Cell Proliferation Vaccines Synthetic General Veterinary biology Reverse Transcriptase Polymerase Chain Reaction ELISPOT Immunogenicity Vaccination SAIDS Vaccines Viral Load biology.organism_classification Virology Semliki forest virus Macaca fascicularis chemistry Viral replication Immunology RNA Viral Animal Science and Zoology Simian Immunodeficiency Virus Vaccinia medicine.drug |
| Zdroj: | Karolinska Institutet |
| Popis: | The immunogenicity and the protective efficacy of a new polyvalent triple vector (DNA/SFV/MVA) based vaccine against mucosal challenge with pathogenic SIV m a c 2 5 1 were investigated. Cynomolgus monkeys (Macaca fascicularis) were primed intradermally with DNA, boosted twice subcutaneously with recombinant Semliki Forest virus (rSFV) and finally intramuscularly with recombinant Modified Vaccinia Virus Ankara strain (rMVA). Both DNA and recombinant viral vectors expressed SIV proteins (Gag, Pol, Tat, Rev, Nef and Env). The vaccinated monkeys developed T helper proliferative responses to viral antigens after the second immunization while interferon (IFN)-γ enzyme-linked immunosorbent spot-forming cell assay (ELISPOT) specific responses appeared only after the last boost with rMVA. Upon intrarectal challenge with pathogenic SIV m a c 2 5 1 , three of four vaccinated monkeys were either fully protected or exhibited a dramatic reduction of virus replication up to undetectable level. A major contribution to this protective effect appeared to be the anamnestic T-cell IFN-γ ELISPOT responses to vaccine antigens (Gag, Rev, Tat, Nef) that mirrored the viral clearance. These results underline the efficacy of a multiprotein approach in combination with a triple vector system of antigen delivery. |
| Databáze: | OpenAIRE |
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