DNA-VLP prime-boost intra-nasal immunization induces cellular and humoral anti-HIV-1 systemic and mucosal immunity with cross-clade neutralizing activity.
The immune response to HIV-1 virus-like particles (VLPs), presenting a clade A Ugandan gp120, has been evaluated in a mouse model by intra-nasal (i.n.) administration by a VLP+VLP homologous or a DNA+VLP heterologous prime-boost immunization protocol, including a HIV-1 DNA gp160/rev plasmid. Furthermore, the effect of the Eurocine lipid-based mucosal L3 adjuvant on the VLP immunogenicity has been assessed as well. The designed heterologous protocol is able to increase the env-specific humoral and cellular immune response, compared to the homologous protocol, which is to some extent increased by the administration of L3-adjuvanted VLP boosting dose. The anti-gag response is statistically increased in both homologous and heterologous protocols, particularly when the VLP boosting dose is adjuvanted. Immune sera from immunized animals exhibit >50% ex vivo neutralizing activity against heterologous A and B-clade viral isolates. An envelope B-cell epitope mapping shows an enhanced response against V3 epitopes all across the C2-V5 region in the heterologous prime-boost immunization strategy. The induction of humoral immunity at mucosal sites, which represents the main port of entry for the HIV-1 infection, is extremely relevant. In this framework, the DNA-VLP heterologous prime-boost protocol appears a promising preventive vaccine approach which can significantly benefit from specific mucosal adjuvants, as the Eurocine L3.
Buonaguro
L
L
Viral Oncogenesis and Immunotherapies & AIDS Reference Center, Ist. Naz. Tumori Fond. G. Pascale, Via Mariano Semmola, 1, 80131 Naples, Italy. irccsvir@unina.it
Devito
C
C
Tornesello
M L
ML
Schröder
U
U
Wahren
B
B
Hinkula
J
J
Buonaguro
F M
FM
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000281:Administration, Intranasal; D000818:Animals; D018604:Epitope Mapping; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D005260:Female; D015483:HIV Antibodies / Q000097:blood / Q000276:immunology*; D019302:HIV Envelope Protein gp160 / Q000276:immunology; D015497:HIV-1 / Q000145:classification* / Q000276:immunology*; D007111:Immunity, Cellular / Q000276:immunology*; D018928:Immunity, Mucosal / Q000276:immunology*; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000097:blood; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D013154:Spleen / Q000166:cytology / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
D016915:AIDS Vaccines; D018985:Epitopes, B-Lymphocyte; D015483:HIV Antibodies; D019302:HIV Envelope Protein gp160; D007074:Immunoglobulin G; D019444:Vaccines, DNA