Design and pre-clinical evaluation of a universal HIV-1 vaccine

One of the big roadblocks in development of HIV-1/AIDS vaccines is the enormous diversity of HIV-1, which could limit the value of any HIV-1 vaccine candidate currently under test. To address the HIV-1 variation, we designed a novel T cell immunogen, designated HIV(CONSV), by assembling the 14 most...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2007-10, Vol.2 (10), p.e984-e984
Main Authors: Létourneau, Sven, Im, Eung-Jun, Mashishi, Tumelo, Brereton, Choechoe, Bridgeman, Anne, Yang, Hongbing, Dorrell, Lucy, Dong, Tao, Korber, Bette, McMichael, Andrew J, Hanke, Tomás
Format: Article
Language:English
Subjects:
Acquired immune deficiency syndrome
Adenoviruses
AIDS
AIDS vaccines
AIDS Vaccines - therapeutic use
Animals
Antigenic determinants
CD4 antigen
CD4-Positive T-Lymphocytes - metabolism
CD8 antigen
CD8-Positive T-Lymphocytes - metabolism
Cloning
Conserved sequence
Councils
Cytotoxicity
Deoxyribonucleic acid
Design
Development and progression
DNA
DNA vaccines
Drug Design
Drug Evaluation, Preclinical
Epitopes
Epitopes - chemistry
Expression vectors
Genes, Viral
Genetic vectors
Health aspects
HIV
HIV-1 - metabolism
Human immunodeficiency virus
Humans
Immunological memory
Immunology
Immunology/Antigen Processing and Recognition
Immunology/Immune Response
Immunology/Immunity to Infections
Infectious Diseases/HIV Infection and AIDS
Interferon-gamma - metabolism
Leukocytes, Mononuclear - metabolism
Lymphocytes
Lymphocytes T
Medical research
Medicine
Memory cells
Mice
Mice, Inbred BALB C
Mycobacterium bovis
Plasmids
Proteomes
Spleen - cytology
T cell receptors
T cells
Test procedures
Vaccines
Virology/Vaccines
Viruses
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:One of the big roadblocks in development of HIV-1/AIDS vaccines is the enormous diversity of HIV-1, which could limit the value of any HIV-1 vaccine candidate currently under test. To address the HIV-1 variation, we designed a novel T cell immunogen, designated HIV(CONSV), by assembling the 14 most conserved regions of the HIV-1 proteome into one chimaeric protein. Each segment is a consensus sequence from one of the four major HIV-1 clades A, B, C and D, which alternate to ensure equal clade coverage. The gene coding for the HIV(CONSV) protein was inserted into the three most studied vaccine vectors, plasmid DNA, human adenovirus serotype 5 and modified vaccine virus Ankara (MVA), and induced HIV-1-specific T cell responses in mice. We also demonstrated that these conserved regions prime CD8(+) and CD4(+) T cell to highly conserved epitopes in humans and that these epitopes, although usually subdominant, generate memory T cells in patients during natural HIV-1 infection. Therefore, this vaccine approach provides an attractive and testable alternative for overcoming the HIV-1 variability, while focusing T cell responses on regions of the virus that are less likely to mutate and escape. Furthermore, this approach has merit in the simplicity of design and delivery, requiring only a single immunogen to provide extensive coverage of global HIV-1 population diversity.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0000984