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