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. 1995 Nov 7;92(23):10693–10697. doi: 10.1073/pnas.92.23.10693

Protective immune responses induced by secretion of a chimeric soluble protein from a recombinant Mycobacterium bovis bacillus Calmette-Guérin vector candidate vaccine for human immunodeficiency virus type 1 in small animals.

M Honda 1, K Matsuo 1, T Nakasone 1, Y Okamoto 1, H Yoshizaki 1, K Kitamura 1, W Sugiura 1, K Watanabe 1, Y Fukushima 1, S Haga 1, et al.
PMCID: PMC40678  PMID: 7479867

Abstract

A recombinant Mycobacterium bovis bacillus Calmette-Guérin (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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Conley A. J., Gorny M. K., Kessler J. A., 2nd, Boots L. J., Ossorio-Castro M., Koenig S., Lineberger D. W., Emini E. A., Williams C., Zolla-Pazner S. Neutralization of primary human immunodeficiency virus type 1 isolates by the broadly reactive anti-V3 monoclonal antibody, 447-52D. J Virol. 1994 Nov;68(11):6994–7000. doi: 10.1128/jvi.68.11.6994-7000.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Garbe T., Harris D., Vordermeier M., Lathigra R., Ivanyi J., Young D. Expression of the Mycobacterium tuberculosis 19-kilodalton antigen in Mycobacterium smegmatis: immunological analysis and evidence of glycosylation. Infect Immun. 1993 Jan;61(1):260–267. doi: 10.1128/iai.61.1.260-267.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Golding H., D'Souza M. P., Bradac J., Mathieson B., Fast P. Neutralization of HIV-1. AIDS Res Hum Retroviruses. 1994 Jun;10(6):633–643. doi: 10.1089/aid.1994.10.633. [DOI] [PubMed] [Google Scholar]
  4. Gorny M. K., Moore J. P., Conley A. J., Karwowska S., Sodroski J., Williams C., Burda S., Boots L. J., Zolla-Pazner S. Human anti-V2 monoclonal antibody that neutralizes primary but not laboratory isolates of human immunodeficiency virus type 1. J Virol. 1994 Dec;68(12):8312–8320. doi: 10.1128/jvi.68.12.8312-8320.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Harboe M., Nagai S., Patarroyo M. E., Torres M. L., Ramirez C., Cruz N. Properties of proteins MPB64, MPB70, and MPB80 of Mycobacterium bovis BCG. Infect Immun. 1986 Apr;52(1):293–302. doi: 10.1128/iai.52.1.293-302.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Huygen K., Abramowicz D., Vandenbussche P., Jacobs F., De Bruyn J., Kentos A., Drowart A., Van Vooren J. P., Goldman M. Spleen cell cytokine secretion in Mycobacterium bovis BCG-infected mice. Infect Immun. 1992 Jul;60(7):2880–2886. doi: 10.1128/iai.60.7.2880-2886.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Matsuo K., Yamaguchi R., Yamazaki A., Tasaka H., Terasaka K., Totsuka M., Kobayashi K., Yukitake H., Yamada T. Establishment of a foreign antigen secretion system in mycobacteria. Infect Immun. 1990 Dec;58(12):4049–4054. doi: 10.1128/iai.58.12.4049-4054.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Matsuo K., Yamaguchi R., Yamazaki A., Tasaka H., Yamada T. Cloning and expression of the Mycobacterium bovis BCG gene for extracellular alpha antigen. J Bacteriol. 1988 Sep;170(9):3847–3854. doi: 10.1128/jb.170.9.3847-3854.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Matthews T. J. Dilemma of neutralization resistance of HIV-1 field isolates and vaccine development. AIDS Res Hum Retroviruses. 1994 Jun;10(6):631–632. doi: 10.1089/aid.1994.10.631. [DOI] [PubMed] [Google Scholar]
  10. McCune J. M., Namikawa R., Kaneshima H., Shultz L. D., Lieberman M., Weissman I. L. The SCID-hu mouse: murine model for the analysis of human hematolymphoid differentiation and function. Science. 1988 Sep 23;241(4873):1632–1639. doi: 10.1126/science.241.4873.1632. [DOI] [PubMed] [Google Scholar]
  11. Mosier D. E., Gulizia R. J., Baird S. M., Wilson D. B. Transfer of a functional human immune system to mice with severe combined immunodeficiency. Nature. 1988 Sep 15;335(6187):256–259. doi: 10.1038/335256a0. [DOI] [PubMed] [Google Scholar]
  12. Muster T., Steindl F., Purtscher M., Trkola A., Klima A., Himmler G., Rüker F., Katinger H. A conserved neutralizing epitope on gp41 of human immunodeficiency virus type 1. J Virol. 1993 Nov;67(11):6642–6647. doi: 10.1128/jvi.67.11.6642-6647.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Salk J., Bretscher P. A., Salk P. L., Clerici M., Shearer G. M. A strategy for prophylactic vaccination against HIV. Science. 1993 May 28;260(5112):1270–1272. doi: 10.1126/science.8098553. [DOI] [PubMed] [Google Scholar]
  14. Stover C. K., de la Cruz V. F., Fuerst T. R., Burlein J. E., Benson L. A., Bennett L. T., Bansal G. P., Young J. F., Lee M. H., Hatfull G. F. New use of BCG for recombinant vaccines. Nature. 1991 Jun 6;351(6326):456–460. doi: 10.1038/351456a0. [DOI] [PubMed] [Google Scholar]
  15. Takahashi H., Merli S., Putney S. D., Houghten R., Moss B., Germain R. N., Berzofsky J. A. A single amino acid interchange yields reciprocal CTL specificities for HIV-1 gp160. Science. 1989 Oct 6;246(4926):118–121. doi: 10.1126/science.2789433. [DOI] [PubMed] [Google Scholar]

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