Virus like particle based strategy to elicit HIV-protective antibodies to the alpha-helic regions of gp41.
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.
Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Via Stamira D'Ancona 20, 20127 Milan, Italy.
C
C
Pastori
D
D
Tudor
L
L
Diomede
A S
AS
Drillet
A
A
Jegerlehner
T A
TA
Röhn
M
M
Bomsel
L
L
Lopalco
D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D000818:Animals; D001435:Bacteriophages / Q000235:genetics; D003601:Cytotoxicity Tests, Immunologic; D004337:Drug Carriers / Q000008:administration & dosage; D005260:Female; D005822:Genetic Vectors; D015483:HIV Antibodies / Q000097:blood*; D015700:HIV Envelope Protein gp41 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D022721:Vaccines, Virosome / Q000008:administration & dosage / Q000276:immunology
D016915:AIDS Vaccines; D004337:Drug Carriers; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; D007074:Immunoglobulin G; D014614:Vaccines, Synthetic; D022721:Vaccines, Virosome; C514787:gp41 protein, Human immunodeficiency virus 1