DNA-VLP prime-boost intra-nasal immunization induces cellular and humoral anti-HIV-1 systemic and mucosal immunity with cross-clade neutralizing activity

Buonaguro, LViral Oncogenesis and Immunotherapies & AIDS Reference Center, Italy (author)

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. © 2007 Elsevier Ltd. All rights reserved.

Devito, CLinköpings universitet,Molekylär virologi,Hälsouniversitetet (author)
Tornesello, MLViral Oncogenesis and Immunotherapies & AIDS Reference Center, Italy (author)
Schröder, UEurocine Vaccines AB, Sweden (author)
Wahren, BKarolinska Institutet (author)
Hinkula, Jorma,1958-Linköpings universitet,Hälsouniversitetet,Molekylär virologi(Swepub:liu)jorhi40 (author)
Buonaguro, FMViral Oncogenesis and Immunotherapies & AIDS Reference Center, Italy (author)
Viral Oncogenesis and Immunotherapies & AIDS Reference Center, ItalyMolekylär virologi (creator_code:org_t)

By the author/editor: Buonaguro, L; Devito, C; Tornesello, ML; Schröder, U; Wahren, B; Hinkula, Jorma, ...; show more...; Buonaguro, FM; show less...

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