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297 HIV-HPV Chimeric Virus-Like Particles Induce HIV-Specific Mucosal and Systemic CTL Responses
J. Liu, W. Shi, W. Li, Y. Huang, M. Velders, W. M. Kast, D. Quinn, M. Mueller, and L. Qiao*
Loyola Univ. Chicago, Maywood, IL, USA
Background: HIV can be transmitted through intestinal mucosa, and HIV-infected blood lymphocytes can circulate to lamina propria of intestinal mucosa, which serves as a reservoir for HIV. Thus, mucosal HIV-specific CTL should be induced to prevent infection and to clear the infected cells. In general, systemic immunization does not induce an efficient mucosal CTL response. Our goal is to develop chimeric virus-like particles (CVLP) of HIV and human papillomavirus (HPV) as a mucosal vaccine because HPV are mucosa-tropic and may be used as delivery vector to mucosa.
Methods: Expression of HPV 16 structural protein L1 leads to formation of VLPs. We made a DNA fragment encoding a peptide containing 2 HLA-A*0201-restricted HIV gp160 epitopes (aa 120(128, aa 814(823) at the C terminus of HPV 16 L1. The HIV-HPV fusion proteins were produced in baculovirus system, and HIV-HPV CVLPs were generated. The immunogenicity of the HIV-HPV CVLPs was determined in HLA-A*0201-transgenic mice. Thus, the mice were orally or systemically immunized and boosted 2 weeks later with the HIV-HPV CVLPs. The lymphocytes from intestinal mucosa and from spleen were isolated from the mice 2 weeks after the booster. HIV-specific CTLs were measured by a standard Cr51 release assay or by gammaIFN-ELISPOT. The mice were also challenged with a papillomavirus pseudovirus (VLPs that have packaged unrelated plasmids) encoding GFP fused with HIV gp 160 120(128.
Results: HLA-A*0201+ target cells pulsed with the HIV peptides were killed by mucosal lymphocytes in the mice orally immunized with the CVLPs but not by those in the mice systemically immunized. Furthermore, HIV-specific CTLs were found among spleen lymphocytes in the mice orally and systemically immunized with the CVLPs by using gammaIFN ELISPOT. Oral immunization with the CVLPs protected mice against mucosal challenge with a pseudovirus encoding the HIV gp160 epitope.
Conclusions: HIV-HPV CVLPs induce HIV-specific mucosal and systemic CTLs. This vaccine may be used to prevent HIV infection and to treat HIV-infected individuals.
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