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

Ramanathan, V D and Kumar, M and Mahalingam, J and Sathyamoorthy, P and Narayanan, P R and Solomon, S and Panicali, D and Chakrabarty, S and Cox, J and Sayeed, E and Ackland, J and Verlinde, C and Voojis, D and Loughran, K and Barin, B and Lombardo, A and Gilmour, J and Stevens, G and Smith, M S and Tarragona-Fiol, T and Hayes, P and Kochhar, S and Excler, J L and Fast, P (2009) 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. AIDS Research and Human Retroviruses, 25 (11). pp. 1107-1185. ISSN Print: 0889-2229; Online: 1931-8405

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Abstract

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 HIVuninfected healthy volunteers who received three intramuscular injections of TBC-M4 at 0, 1, and 6 months of 5�107 plaque-forming units (pfu) (low dosage, LD) (n¼12) or 2.5�108 pfu (high dosage, HD) (n¼12) or placebo (n¼8). 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-g 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=106 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.

Item Type:	Article
Uncontrolled Keywords:	immunogenicity; HIV; vaccine, India
Subjects:	Tuberculosis > Laboratory Research > Pathological Tuberculosis > Vaccinology HIV
Divisions:	Basic Science Research > Clinical Pathology
Depositing User:	Dr. Rathinasabapati R
Date Deposited:	22 Nov 2017 07:56
Last Modified:	02 Mar 2021 06:59
URI:	http://eprints.nirt.res.in/id/eprint/980

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