Safety and immunogenicity of DNA prime and modified vaccinia ankara virus-HIV subtype C vaccine boost in healthy adults.
A randomized, double-blind, placebo-controlled phase I trial was conducted in 32 HIV-uninfected healthy volunteers to assess the safety and immunogenicity of 3 doses of DNA vaccine (Advax) plus 1 dose of recombinant modified vaccinia virus Ankara (MVA) (TBC-M4) or 3 doses of TBC-M4 alone (groups A and B, respectively). Both vaccine regimens were found to be safe and well tolerated. Gamma interferon (IFN-γ) enzyme-linked immunosorbent spot (ELISPOT) assay responses were detected in 1/10 (10%) individuals in group A after three Advax primes and in 9/9 individuals (100%) after the MVA boost. In group B, IFN-γ ELISPOT responses were detected in 6/12 (50%) and 7/11 (64%) individuals after the second and third MVA vaccinations, respectively. Responses to all vaccine components, but predominantly to Env, were seen. The breadth and magnitude of the T cell response and viral inhibition were greater in group A than in group B, indicating that the quality of the T-cell response was enhanced by the DNA prime. Intracellular cytokine staining indicated that the T-cell responses were polyfunctional but were skewed toward Env with a CD4(+) phenotype. At 2 weeks after the last vaccination, HIV-specific antibody responses were detected in all (100%) group B and 1/11 (9.1%) group A vaccinees. Vaccinia virus-specific responses were detected in all (100%) group B and 2/11 (18.2%) group A vaccinees. In conclusion, HIV-specific T-cell responses were seen in the majority of volunteers in groups A and B but with a trend toward greater quality of the T-cell response in group A. Antibody responses were better in group B than in group A.
IAVI Human Immunology Laboratory, Imperial College, London, United Kingdom.
Peter
P
Hayes
Jill
J
Gilmour
Andrea
A
von Lieven
Dilbinder
D
Gill
Lorna
L
Clark
Jakub
J
Kopycinski
Hannah
H
Cheeseman
Amy
A
Chung
Galit
G
Alter
Len
L
Dally
Devika
D
Zachariah
Angela
A
Lombardo
James
J
Ackland
Eddy
E
Sayeed
Akil
A
Jackson
Marta
M
Boffito
Brian
B
Gazzard
Patricia E
PE
Fast
Josephine H
JH
Cox
Dagna
D
Laufer
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D000328:Adult; D004337:Drug Carriers / Q000008:administration & dosage; D058501:Enzyme-Linked Immunospot Assay; D006678:HIV / Q000235:genetics / Q000276:immunology*; D015483:HIV Antibodies / Q000097:blood; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D010919:Placebos / Q000008:administration & dosage; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics
D016915:AIDS Vaccines; D004337:Drug Carriers; D015483:HIV Antibodies; D010919:Placebos; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D007371:Interferon-gamma