The concept of combination immunization (i.e. the so-called """"""""rime and boost"""""""" regimen) was developed to take advantage of the diverse immune responses generated by different immunogens presented endogenously or exogenously. The promise of this approach was first demonstrated by priming with recombinant vaccinia virus and boosting with subunit envelope glycoproteins. Vaccines typically generated by cytotoxic T- lymphocyte (CTL) responses as well as neutralizing antibodies. Protection against experimental SIV or SHIV challenge by combination immunization has been observed in a number of animal model. Several variations on the theme of combination immunization strategy have also been developed in the past several years. These include the use of other viruses (e.g., canarypox virus) as well as DNA vectors for priming, and immunogens of different sources and complexity for boosting, DNA priming and subunit protein boosting is a key component in the present proposal of combined active and passive immunoprophylaxis against intrapartum clade C HIV-1 transmission. The overall goal of the Immunogen Core is to provide immunogens for active immunization studies (Project 3), for combination passive and active immunoprophylaxis (Project 2) and to provide reagents for the characterization of monoclonal antibodies (Project 1) and CTL responses (Project 3).
The specific aims of this Core are: (1) To generate recombinant vaccinia viruses expressing the envelope glycoproteins of clade C isolates of HIV-1 resulting from intrapartum transmissions; (2) To characterize the structural, antigenic and functional integrity of these proteins; (3) To optimize conditions for the production and purification of these proteins; and (4) To scale up the production and the purification of the HIV-1 clade C envelope and SIVmac239 core proteins for studies outlines in Program Projects.
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