PROTECTIVE IMMUNE-RESPONSES INDUCED BY SECRETION OF A CHIMERIC SOLUBLE-PROTEIN FROM A RECOMBINANT MYCOBACTERIUM-BOVIS BACILLUS-CALMETTE-GUERIN VECTOR CANDIDATE VACCINE FOR HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 IN SMALL ANIMALS

A recombinant Mycobacterium bovis bacillus Calmette-Guerin (BCG) vecto r-based vaccine that secretes the V3 principal neutralizing epitope of human immunodeficiency virus (HIV) could induce immune response to th e epitope and prevent the viral infection. By using the Japanese conse nsus sequence of HIV-1, we successfully constructed chimeric protein s ecretion vectors by selecting an appropriate insertion site of a carri er protein and established the principal neutralizing determinant (PND )-peptide secretion system in BCG. The recombinant BCG (rBCG)-inoculat ed guinea pigs were initially screened by delayed-type hypersensitivit y (DTH) skin reactions to the PND peptide, followed by passive transfe r of the DTH by the systemic route, Further, immunization of mice with the rBCG resulted in induction of cytotoxic T lymphocytes. The guinea pig immune antisera showed elevated titers to the PND peptide and neu tralized HIVMN, and administration of serum IgG from the vaccinated gu inea pigs was effective in completely blocking the HIV infection in th ymus/liver transplanted severe combined immunodeficiency (SCID)/hu or SCID/PBL mice. In addition, the immune serum IgG was shown to neutrali ze primary field isolates of HIV that match the neutralizing sequence motif by a peripheral blood mononuclear fell-based virus neutralizatio n assay. The data support the idea that the antigen-secreting rBCG sys tem can be used as a tool for development of HIV vaccines.