Adjuvanted HLA-supertype restricted subdominant peptides induce new T-cell immunity during untreated HIV-1-infection

Ingrid Karlsson; Lea Brandt; Lasse Vinner; Ingrid Kromann; Lars Vibe Andreasen; Peter Andersen; Jan Gerstoft; Gitte Kronborg; Anders Fomsgaard

doi:10.1016/j.clim.2012.12.005

Adjuvanted HLA-supertype restricted subdominant peptides induce new T-cell immunity during untreated HIV-1-infection

Clin Immunol. 2013 Feb;146(2):120-30. doi: 10.1016/j.clim.2012.12.005. Epub 2012 Dec 21.

Authors

Ingrid Karlsson¹, Lea Brandt, Lasse Vinner, Ingrid Kromann, Lars Vibe Andreasen, Peter Andersen, Jan Gerstoft, Gitte Kronborg, Anders Fomsgaard

Affiliation

¹ Department of Virology, Statens Serum Institut, 2300 Copenhagen, Denmark.

PMID: 23314272
DOI: 10.1016/j.clim.2012.12.005

Abstract

We investigated the potential of inducing additional T-cell immunity during chronic HIV-1 infection directed to subdominant HIV-1 epitopes from common HLA-supertypes. Ten treatment-naïve HIV-1-infected individuals were immunized with peptides in the adjuvant CAF01. One individual received placebo. T-cell immunogenicity was examined longitudinally by a flow cytometry (CD107a, IFNγ, TNFα, IL-2 and/or MIP1β expression) as well as IFNγ ELISPOT. Safety was evaluated by clinical follow up combined with monitoring of biochemistry, hematology, CD4 T-cell counts and viral load. New CD4 and CD8 T-cell responses specific for one or more vaccine epitopes were induced in 10/10 vaccinees. The responses were dominated by CD107a and MIP1β expression. There were no significant changes in HIV-1 viral load or CD4 T-cell counts. Our study demonstrates that the peptide/CAF01 vaccine is safe and that it is possible to generate new HIV-1 T-cell responses to defined epitopes in treatment-naïve HIV-1-infected individuals.

Trial registration: ClinicalTrials.gov NCT01009762.

Publication types

Clinical Trial, Phase I
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adjuvants, Immunologic / administration & dosage
Adjuvants, Immunologic / therapeutic use*
Adolescent
Adult
CD4-Positive T-Lymphocytes / immunology*
CD4-Positive T-Lymphocytes / metabolism
CD4-Positive T-Lymphocytes / virology
CD8-Positive T-Lymphocytes / immunology*
CD8-Positive T-Lymphocytes / metabolism
CD8-Positive T-Lymphocytes / virology
Epitopes, T-Lymphocyte / administration & dosage
Epitopes, T-Lymphocyte / immunology
Epitopes, T-Lymphocyte / therapeutic use*
Female
HIV Infections / immunology*
HIV Infections / prevention & control
HIV Infections / therapy*
HLA-A Antigens / administration & dosage
HLA-A Antigens / genetics
HLA-B Antigens / administration & dosage
HLA-B Antigens / genetics
HLA-C Antigens / administration & dosage
HLA-C Antigens / genetics
Humans
Immunodominant Epitopes / administration & dosage
Immunodominant Epitopes / immunology
Immunodominant Epitopes / therapeutic use*
Male
Middle Aged
Peptides / administration & dosage
Peptides / immunology
Peptides / therapeutic use*
Single-Blind Method
Young Adult

Substances

Adjuvants, Immunologic
Epitopes, T-Lymphocyte
HLA-A Antigens
HLA-B Antigens
HLA-C Antigens
Immunodominant Epitopes
Peptides

Associated data

ClinicalTrials.gov/NCT01009762