Virus like particle based strategy to elicit HIV-protective antibodies to the alpha-helic regions of gp41

Abstract Natural antibodies to gp41 inhibit HIV-1 replication through the recognition of two different regions, corresponding to the leucine zipper motif in the HR1 alpha-helix and to another motif within HR2 region, hosting 2F5 and 4E10 epitope. This study aimed at reproducing such protective respo...

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Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2012-09, Vol.431 (1), p.1-11
Main Authors: Pastori, C, Tudor, D, Diomede, L, Drillet, A.S, Jegerlehner, A, Röhn, T.A, Bomsel, M, Lopalco, L
Format: Article
Language:English
Subjects:
ADCC
AIDS Vaccines - administration & dosage
AIDS Vaccines - immunology
Animals
Bacteriophages - genetics
C-Terminus
Cytotoxicity
Cytotoxicity Tests, Immunologic
Drug Carriers - administration & dosage
Epitopes
Female
Genetic Vectors
glycoprotein gp41
gp41
HIV
HIV Antibodies - blood
HIV Envelope Protein gp41 - immunology
HIV-1 - immunology
Human immunodeficiency virus 1
Immunogenicity
Immunoglobulin G
Immunoglobulin G - blood
Infection
Infectious Disease
Infectivity
Leucine zipper proteins
Mice
Mice, Inbred BALB C
Mucosa
N-Terminus
Neutralizing antibodies
Replication
Vaccination
Vaccines, Synthetic - administration & dosage
Vaccines, Synthetic - immunology
Vaccines, Virosome - administration & dosage
Vaccines, Virosome - immunology
VLP
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Summary:Abstract Natural antibodies to gp41 inhibit HIV-1 replication through the recognition of two different regions, corresponding to the leucine zipper motif in the HR1 alpha-helix and to another motif within HR2 region, hosting 2F5 and 4E10 epitope. This study aimed at reproducing such protective responses through VLP vaccination. Six regions covering the alpha-helical regions of gp41 were conjugated to the surface of AP205 phage-based VLPs. Once administered in mice via systemic or mucosal route, these immunogens elicited high titers of gp41-specific IgG. Immunogenicity and HIV infectivity reduction were obtained either with HR2 regions or with peptides where aminoacid strings were added to either the C-terminus or N-terminus of core epitope in HR1 region. Antibody-dependent cell cytotoxicity (ADCC) activity was induced by one of the HR2 epitopes only. These results may have relevant implications for the development of new vaccinal approaches against HIV infection.
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2012.05.005