Therapeutic vaccination expands and improves the function of the HIV-specific memory T-cell repertoire.
Details
Serval ID
serval:BIB_6201A36634D7
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Therapeutic vaccination expands and improves the function of the HIV-specific memory T-cell repertoire.
Journal
The Journal of infectious diseases
Working group(s)
VRC 101 Study Team
Contributor(s)
Holman L., Hendel C., Plummer S., Novik L., Larkin B., Rucker S., Costner P., Goswami T., Read S., Leitman S., Decederfelt H., Starling J., Alley T., Jones R., Johnson D., Jones S., Sitar S., Stanford L.C., Washington-Lewis R., Thompson E., Rhone K., Zaia P.
ISSN
1537-6613 (Electronic)
ISSN-L
0022-1899
Publication state
Published
Issued date
15/06/2013
Peer-reviewed
Oui
Volume
207
Number
12
Pages
1829-1840
Language
english
Notes
Publication types: Clinical Trial, Phase I ; Journal Article ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
The licensing of herpes zoster vaccine has demonstrated that therapeutic vaccination can help control chronic viral infection. Unfortunately, human trials of immunodeficiency virus (HIV) vaccine have shown only marginal efficacy.
In this double-blind study, 17 HIV-infected individuals with viral loads of <50 copies/mL and CD4(+) T-cell counts of >350 cells/µL were randomly assigned to the vaccine or placebo arm. Vaccine recipients received 3 intramuscular injections of HIV DNA (4 mg) coding for clade B Gag, Pol, and Nef and clade A, B, and C Env, followed by a replication-deficient adenovirus type 5 boost (10(10) particle units) encoding all DNA vaccine antigens except Nef. Humoral, total T-cell, and CD8(+) cytotoxic T-lymphocyte (CTL) responses were studied before and after vaccination. Single-copy viral loads and frequencies of latently infected CD4(+) T cells were determined.
Vaccination was safe and well tolerated. Significantly stronger HIV-specific T-cell responses against Gag, Pol, and Env, with increased polyfunctionality and a broadened epitope-specific CTL repertoire, were observed after vaccination. No changes in single-copy viral load or the frequency of latent infection were observed.
Vaccination of individuals with existing HIV-specific immunity improved the magnitude, breadth, and polyfunctionality of HIV-specific memory T-cell responses but did not impact markers of viral control.
NCT00270465.
In this double-blind study, 17 HIV-infected individuals with viral loads of <50 copies/mL and CD4(+) T-cell counts of >350 cells/µL were randomly assigned to the vaccine or placebo arm. Vaccine recipients received 3 intramuscular injections of HIV DNA (4 mg) coding for clade B Gag, Pol, and Nef and clade A, B, and C Env, followed by a replication-deficient adenovirus type 5 boost (10(10) particle units) encoding all DNA vaccine antigens except Nef. Humoral, total T-cell, and CD8(+) cytotoxic T-lymphocyte (CTL) responses were studied before and after vaccination. Single-copy viral loads and frequencies of latently infected CD4(+) T cells were determined.
Vaccination was safe and well tolerated. Significantly stronger HIV-specific T-cell responses against Gag, Pol, and Env, with increased polyfunctionality and a broadened epitope-specific CTL repertoire, were observed after vaccination. No changes in single-copy viral load or the frequency of latent infection were observed.
Vaccination of individuals with existing HIV-specific immunity improved the magnitude, breadth, and polyfunctionality of HIV-specific memory T-cell responses but did not impact markers of viral control.
NCT00270465.
Keywords
AIDS Vaccines/immunology, Adult, Amino Acid Sequence, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes/immunology, CD8-Positive T-Lymphocytes/immunology, Double-Blind Method, Epitope Mapping, Epitopes, T-Lymphocyte/immunology, Follow-Up Studies, HIV/immunology, HIV Infections/immunology, HIV Infections/therapy, HIV Infections/virology, Humans, Immunity, Humoral, Male, Middle Aged, Molecular Sequence Data, Recombinant Proteins, T-Lymphocyte Subsets/immunology, T-Lymphocytes, Cytotoxic/immunology, Vaccination, Viral Load, Virus Latency, HIV, cytotoxic T lymphocytes, humoral immunity, therapy, vaccination, viral latency
Pubmed
Web of science
Open Access
Yes
Create date
28/02/2022 12:45
Last modification date
23/03/2024 8:24