AEGiS-11IAC: HIV-1 Pr55gag virus-like particles allow the access of polyproteins and defined epitopes to the MHC-I presentation-pathway.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

HIV-1 Pr55gag virus-like particles allow the access of polyproteins and defined epitopes to the MHC-I presentation-pathway.

Int Conf AIDS 1996 Jul 7-12; 11:7 (abstract no. Mo.A.156)
Ludwig D, Schirmbeck R, Reimann J, Wolf H, Wagner R; Institut fur Medizinische Microbiologie und Hygiene, Universitat Regensburg, Regensburg, Germany. Fax: +49 941 944 6402.

OBJECTIVE: In many viral infections, cell mediated immunity, in particular the cytotoxic T-cell response, plays a key role in the control of a viral infection. There is striking evidence to suggest that this may be also in the case of an HIV infection. Therefore we tested the capacity of different types of chimeric Pr55gag VLPs of trafficking defined CTL epitopes or complex polyproteins to the MHC-I presentation pathway. Method: We developed an autologous, safe and non replicating carrier system, basing on recombinant, non infectious HIV-1 Pr55 lipoprotein particles (VLPs) To expand the immunogenicity of these VLPs, defined domains within the Pr55 polyprotein were replaced by selected CTL epitopes such as the third variable loop V3 of the HIV-1 envelope protein gp120 (type I VLPs). Alternatively chimeric HIV-1 envelope proteins were stably anchored on the surface of these VLPs by a heterologous type I transmembrane moiety of the EBV envelope protein gp350/220 (type II VLPs). To test the capacity of VLPs to induce a V3-loop specific MHC-I restricted CTL response, different VLP preparations were produced in insect cells by using recombinant baculoviruses and purified by sedimentation through a sucrose cushion.

RESULTS: Immunisation of BALB/c mice with different types of chimeric Pr55gag/V3 VLP resulted in the induction of a strong CD8+ CTL response in vivo, irrelevant of the position of the V3 loop within the comlex carrier component. Different routes of immunisation (s.c., i.p., i.v.) as well as antigen doses in a range of 1-20 micrograms have been proven as equally effective. In contrast only a week CTL-response was elicited by VLP adsorbed to Alum or emulsified in IFA.

CONCLUSIONS: Pr55 based lipoprotein particles resemble a novel and potent immunogen, which efficiently mediates the transport of small peptides and complex polyproteins to the MHC-class I antigen presentation pathway. The importance of these data for the development of a second generation of HIV candidate vaccines will be discussed.

Keywords: AEGIS, HIV, Epitopes, HIV Envelope Protein gp120, Major Histocompatibility Complex, AIDS Vaccines, HIV-1, T-Lymphocytes, Cytotoxic, Gene Products, gag, HIV Antibodies, Polyproteins, Gene Products, env, Histocompatibility Antigens Class I, HIV Infections, HIV Core Protein p24, HIV Envelope Protein gp160, Antigens, CD8, Animal, Mice, immunology, genetics, ICA11

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