Subtype C gp140 Vaccine Boosts Immune Responses Primed by the South African AIDS Vaccine Initiative DNA-C2 and MVA-C HIV Vaccines after More than a 2-Year Gap.
A phase I safety and immunogenicity study investigated South African AIDS Vaccine Initiative (SAAVI) HIV-1 subtype C (HIV-1C) DNA vaccine encoding Gag-RT-Tat-Nef and gp150, boosted with modified vaccinia Ankara (MVA) expressing matched antigens. Following the finding of partial protective efficacy in the RV144 HIV vaccine efficacy trial, a protein boost with HIV-1 subtype C V2-deleted gp140 with MF59 was added to the regimen. A total of 48 participants (12 U.S. participants and 36 Republic of South Africa [RSA] participants) were randomized to receive 3 intramuscular (i.m.) doses of SAAVI DNA-C2 of 4 mg (months 0, 1, and 2) and 2 i.m. doses of SAAVI MVA-C of 1.45 × 10(9) PFU (months 4 and 5) (n = 40) or of a placebo (n = 8). Approximately 2 years after vaccination, 27 participants were rerandomized to receive gp140/MF59 at 100 μg or placebo, as 2 i.m. injections, 3 months apart. The vaccine regimen was safe and well tolerated. After the DNA-MVA regimen, CD4(+) T-cell and CD8(+) T-cell responses occurred in 74% and 32% of the participants, respectively. The protein boost increased CD4(+) T-cell responses to 87% of the subjects. All participants developed tier 1 HIV-1C neutralizing antibody responses as well as durable Env binding antibodies that recognized linear V3 and C5 peptides. The HIV-1 subtype C DNA-MVA vaccine regimen showed promising cellular immunogenicity. Boosting with gp140/MF59 enhanced levels of binding and neutralizing antibodies as well as CD4(+) T-cell responses to HIV-1 envelope. (This study has been registered at ClinicalTrials.gov under registration no. NCT00574600 and NCT01423825.).
Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa Glenda.gray@mrc.ac.za.|South African Medical Research Council, Cape Town, South Africa.
Glenda E
GE
Gray
Fenway Health and Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Kenneth H
KH
Mayer
Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Marnie L
ML
Elizaga
Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
Linda-Gail
LG
Bekker
DAIDS, NIAID, NIH, Washington, DC, USA.
Mary
M
Allen
National Institute for Communicable Diseases of the National Health Laboratory Services, Johannesburg, South Africa.
Lynn
L
Morris
Duke University, Durham, North Carolina, USA.
David
D
Montefiori
Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Stephen C
SC
De Rosa
Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Alicia
A
Sato
Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Niya
N
Gu
Duke University, Durham, North Carolina, USA.
Georgia D
GD
Tomaras
South African Medical Research Council, Cape Town, South Africa.
Timothy
T
Tucker
Novartis Vaccines, Cambridge, Massachusetts, USA.
Susan W
SW
Barnett
National Institute for Communicable Diseases of the National Health Laboratory Services, Johannesburg, South Africa.
Nonhlanhla N
NN
Mkhize
Duke University, Durham, North Carolina, USA.
Xiaoying
X
Shen
Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
Katrina
K
Downing
Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.|National Health Laboratory Service, Cape Town, South Africa.
Carolyn
C
Williamson
DAIDS, NIAID, NIH, Washington, DC, USA.
Michael
M
Pensiero
Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Lawrence
L
Corey
Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.|National Health Laboratory Service, Cape Town, South Africa.
Anna-Lise
AL
Williamson
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000145:classification / Q000276:immunology*; D000163:Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D000293:Adolescent; D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood*; D018791:CD4 Lymphocyte Count; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D015483:HIV Antibodies / Q000097:blood / Q000276:immunology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007115:Immunization Schedule; D007117:Immunization, Secondary / Q000009:adverse effects; D007273:Injections, Intramuscular; D008297:Male; D013019:South Africa; D013997:Time Factors; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D014615:Vaccinia / Q000235:genetics / Q000276:immunology; D055815:Young Adult; D054299:env Gene Products, Human Immunodeficiency Virus / Q000008:administration & dosage / Q000276:immunology*
D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D019444:Vaccines, DNA; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1