A Phase 1 Study to Evaluate the Safety and Immunogenicity of a Recombinant HIV Type 1 Subtype C-Modified Vaccinia Ankara Virus Vaccine Candidate in Indian Volunteers
| Autor: | Sonali Kochhar, Jayashri Mahalingam, Kelley Loughran, Vadakkuppatu Devasenapathi Ramanathan, Peter Hayes, Makesh Kumar, Eddy Sayeed, Tony Tarragona-Fiol, Angela Lombardo, Paranji Ramaiyengar Narayanan, Suniti Solomon, Patricia E. Fast, Sekhar Chakrabarty, Carl Verlinde, Michelle Seth Smith, Pattabiraman Sathyamoorthy, Dani Vooijs, Dennis Panicali, James Ackland, Jill Gilmour, Gwynneth Stevens, Jean-Louis Excler, Josephine H. Cox, Burc Barin |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
Male Modified vaccinia Ankara Adolescent Human Immunodeficiency Virus Proteins Immunology India HIV Infections Vaccinia virus HIV Antibodies Virus Interferon-gamma Young Adult Double-Blind Method Virology Vaccines DNA Humans Medicine Poxviridae Orthopoxvirus AIDS Vaccines Reactogenicity biology business.industry ELISPOT Immunogenicity Middle Aged biology.organism_classification Vaccination Treatment Outcome Infectious Diseases HIV-1 Female business |
| Zdroj: | AIDS Research and Human Retroviruses. 25:1107-1116 |
| ISSN: | 1931-8405 0889-2229 |
| DOI: | 10.1089/aid.2009.0096 |
| Popis: | A recombinant modified vaccinia Ankara virus vaccine candidate (TBC-M4) expressing HIV-1 subtype C env, gag, tat-rev, and nef-RT genes was tested in a randomized, double-blind, dose escalation Phase I trial in 32 HIV-uninfected healthy volunteers who received three intramuscular injections of TBC-M4 at 0, 1, and 6 months of 5 x 10(7) plaque-forming units (pfu) (low dosage, LD) (n = 12) or 2.5 x 10(8) pfu (high dosage, HD) (n = 12) or placebo (n = 8). Local and systemic reactogenicity was experienced by approximately 67% and 83% of vaccine recipients, respectively. The reactogenicity events were mostly mild in severity. Severe but transient systemic reactogenicity was seen in one volunteer of the HD group. No vaccine-related serious adverse events or events suggesting perimyocarditis were seen. A higher frequency of local reactogenicity events was observed in the HD group. Cumulative HIV-specific IFN-gamma ELISPOT responses were detected in frozen PBMCs from 9/11 (82%), 12/12 (100%), and 1/8 (13%) volunteers after the third injection of the LD, HD, and placebo groups, respectively. Most of the responses were to gag and env proteins (maximum of 430 SFU/10(6) PBMCs) persisting across multiple time points. HIV-specific ELISA antibody responses were detected in 10/11, 12/12, and 0/8 volunteers post-third vaccination, in the LD, HD, and placebo groups, respectively. No neutralizing activity against HIV-1 subtype C isolates was detected. TBC-M4 appears to be generally safe and well-tolerated. The immune response detected was dose dependent, modest in magnitude, and directed mostly to env and gag proteins, suggesting further evaluation of this vaccine in a prime-boost regimen. |
| Databáze: | OpenAIRE |
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