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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.


Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10693-7. Unique Identifier :

A recombinant Mycobacterium bovis bacillus Calmette-Guerin (BCG) vector-based vaccine that secretes the V3 principal neutralizing epitope of human immunodeficiency virus (HIV) could induce immune response to the epitope and prevent the viral infection. By using the Japanese consensus sequence of HIV-1, we successfully constructed chimeric protein secretion vectors by selecting an appropriate insertion site of a carrier protein and established the principal neutralizing determinant (PND)-peptide secretion system in BCG. The recombinant BCG (rBCG)-inoculated guinea pigs were initially screened by delayed-type hypersensitivity (DTH) skin reactions to the PND peptide, followed by passive transfer 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 neutralized HIVMN, and administration of serum IgG from the vaccinated guinea pigs was effective in completely blocking the HIV infection in thymus/liver transplanted severe combined immunodeficiency (SCID)/hu or SCID/PBL mice. In addition, the immune serum IgG was shown to neutralize primary field isolates of HIV that match the neutralizing sequence motif by a peripheral blood mononuclear cell-based virus neutralization assay. The data support the idea that the antigen-secreting rBCG system can be used as a tool for development of HIV vaccines.

Amino Acid Sequence Animal Antibodies, Viral/BLOOD AIDS Vaccines/*IMMUNOLOGY Base Sequence Enzyme-Linked Immunosorbent Assay Genetic Vectors Guinea Pigs Human HIV Envelope Protein gp120/*IMMUNOLOGY HIV Infections/*PREVENTION & CONTROL HIV-1/IMMUNOLOGY Immunization, Passive Mice Mice, SCID Middle Age Molecular Sequence Data Mycobacterium bovis/GENETICS Neutralization Tests Peptide Fragments/*IMMUNOLOGY Skin Tests Support, Non-U.S. Gov't T-Lymphocytes, Cytotoxic Vaccines, Synthetic/*IMMUNOLOGY Viral Proteins/SECRETION JOURNAL ARTICLE


Information in this article was accurate in February 28, 1996. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.