title: 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.
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 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.
authors: Tuberculosis Research Centre, Chennai, India.
authors: Vadakkuppatu Devasenapathi
authors: VD
authors: Ramanathan
authors: Makesh
authors: M
authors: Kumar
authors: Jayashri
authors: J
authors: Mahalingam
authors: Pattabiraman
authors: P
authors: Sathyamoorthy
authors: Paranji Ramaiyengar
authors: PR
authors: Narayanan
authors: Suniti
authors: S
authors: Solomon
authors: Dennis
authors: D
authors: Panicali
authors: Sekhar
authors: S
authors: Chakrabarty
authors: Josephine
authors: J
authors: Cox
authors: Eddy
authors: E
authors: Sayeed
authors: James
authors: J
authors: Ackland
authors: Carl
authors: C
authors: Verlinde
authors: Dani
authors: D
authors: Vooijs
authors: Kelley
authors: K
authors: Loughran
authors: Burc
authors: B
authors: Barin
authors: Angela
authors: A
authors: Lombardo
authors: Jill
authors: J
authors: Gilmour
authors: Gwynneth
authors: G
authors: Stevens
authors: Michelle Seth
authors: MS
authors: Smith
authors: Tony
authors: T
authors: Tarragona-Fiol
authors: Peter
authors: P
authors: Hayes
authors: Sonali
authors: S
authors: Kochhar
authors: Jean-Louis
authors: JL
authors: Excler
authors: Patricia
authors: P
authors: Fast
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D004311:Double-Blind Method; D005260:Female; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology; D054298:Human Immunodeficiency Virus Proteins / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007194:India; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics*; D055815:Young Adult
chemical_list: D016915:AIDS Vaccines; D015483:HIV Antibodies; D054298:Human Immunodeficiency Virus Proteins; D019444:Vaccines, DNA; D007371:Interferon-gamma