Specific immune response and pathological findings in BALB/c mice inoculated with recombinant BCG expressing HIV-1 antigen.

Recombinant BCGs (rBCGs) containing extrachromosomal plasmids with different HIV-1 insert sequences: nef, env (V3J1 and E9Q), gag p17 or whole gag p55 were evaluated for their immunogenicity, safety and persistent infection in BALB/c mice. Animal injected with, rBCG-plJKV3J1, rBCG-pSO gag p17 or rBCG-pSO gag p55 could elicit lymphocyte proliferation as tested by specific HIV-1 peptides or protein antigen. Inoculation with various concentration of rBCG-pSO gag p55 generated satisfactory specific lymphocyte proliferation in dose escalation trials. The rBCG-pSO gag p55 recovered from spleen tissues at different time interval post-inoculation could express the HIV protein as determined by ELISA p24 antigen detection kit. This result indicated that the extrachromosomal plasmid was stable and capable to express Gag protein. It was also demonstrated that rBCGs did not cause serious pathological change in the inoculated animals. The present study suggested the role of BCG as a potential vehicle for using in HIV vaccine development.

[1]  H. Kiyono,et al.  Combined intrarectal/intradermal inoculation of recombinant Mycobacterium bovis bacillus Calmette-Guérin (BCG) induces enhanced immune responses against the inserted HIV-1 V3 antigen. , 2002, Vaccine.

[2]  Oral recombinant Mycobacterium bovis bacillus Calmette-Guérin expressing HIV-1 antigens as a freeze-dried vaccine induces long-term, HIV-specific mucosal and systemic immunity. , 2002, Clinical immunology.

[3]  J. Schneider-Mergener,et al.  Identification of T helper cell-recognized epitopes in the chitinase of the filarial nematode Onchocerca volvulus. , 2002, Vaccine.

[4]  H. Kiyono,et al.  HIV Mucosal Vaccine: Nasal Immunization with rBCG-V3J1 Induces a Long Term V3J1 Peptide-Specific Neutralizing Immunity in Th1- and Th2-Deficient Conditions1 , 2001, The Journal of Immunology.

[5]  C. Rouzioux,et al.  Patient-Specific Cytotoxic T-Lymphocyte Cross-Recognition of Naturally Occurring Variants of a Human Immunodeficiency Virus Type 1 (HIV-1) p24gagEpitope by HIV-1-Infected Children , 2001, Journal of Virology.

[6]  K. Ruxrungtham,et al.  Safety and immunogenicity of Bacillus Calmette-Guerin vaccine in children born to HIV-1 infected women. , 2000, The Southeast Asian journal of tropical medicine and public health.

[7]  R. Young,et al.  Immune responses induced by BCG recombinant for human papillomavirus L1 and E7 proteins. , 2000, Vaccine.

[8]  D. Birx,et al.  Cross-clade cytotoxic T cell response to human immunodeficiency virus type 1 proteins among HLA disparate North Americans and Thais. , 1998, The Journal of infectious diseases.

[9]  S. Matsumoto,et al.  Recombinant Mycobacterium bovis Bacillus Calmette-Guérin Secreting Merozoite Surface Protein 1 (MSP1) Induces Protection against Rodent Malaria Parasite Infection Depending on MSP1-stimulated Interferon γ and Parasite-specific Antibodies , 1998, The Journal of experimental medicine.

[10]  P. Kaleebu,et al.  Cross‐clade recognition of p55 by cytotoxic T lymphocytes in HIV‐1 infection , 1998, AIDS.

[11]  J. Sterne,et al.  Does the efficacy of BCG decline with time since vaccination? , 1998, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[12]  B. Walker,et al.  Cytotoxic T-lymphocyte cross-reactivity among different human immunodeficiency virus type 1 clades: implications for vaccine development , 1997, Journal of virology.

[13]  F. Oftung,et al.  T-Cell epitope mapping the PorB protein of serogroup B Neisseria meningitidis in B10 congenic strains of mice. , 1997, Clinical immunology and immunopathology.

[14]  S. Matsumoto,et al.  A stable Escherichia coli-mycobacteria shuttle vector 'pSO246' in Mycobacterium bovis BCG. , 1996, FEMS microbiology letters.

[15]  Y. Okamoto,et al.  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. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[16]  M. Hanson,et al.  Efficacy and safety of live recombinant BCG vaccines. , 1995, Developments in biological standardization.

[17]  S. Langermann,et al.  Systemic and mucosal immunity induced by BCG vector expressing outer-surface protein A of Borrelia burgdorferi , 1994, Nature.

[18]  M. Hanson,et al.  Protective humoral response against pneumococcal infection in mice elicited by recombinant bacille Calmette-Guerin vaccines expressing pneumococcal surface protein A , 1994, The Journal of experimental medicine.

[19]  K. Ikuta,et al.  Cytotoxic T lymphocyte response in mice induced by a recombinant BCG vaccination which produces an extracellular alpha antigen that fused with the human immunodeficiency virus type 1 envelope immunodominant domain in the V3 loop. , 1994, Vaccine.

[20]  M. Hanson,et al.  Protective immunity elicited by recombinant bacille Calmette-Guerin (BCG) expressing outer surface protein A (OspA) lipoprotein: a candidate Lyme disease vaccine , 1993, The Journal of experimental medicine.

[21]  R. Young,et al.  Humoral and cell-mediated immune responses to live recombinant BCG–HIV vaccines , 1991, Nature.

[22]  W. Jacobs,et al.  New use of BCG for recombinant vaccines , 1991, Nature.

[23]  K. Kobayashi,et al.  Establishment of a foreign antigen secretion system in mycobacteria , 1990, Infection and immunity.

[24]  T. Yamada,et al.  Cloning and characterization of the gene for immunogenic protein MPB64 of Mycobacterium bovis BCG , 1989, Infection and immunity.

[25]  I. Azuma,et al.  Adjuvant activity of mycobacterial fractions. III. Adjuvant effect of cell wall of Mycobacterium bovis BCG on cell-mediated cytotoxicity in mice. , 1975, Japanese journal of microbiology.

[26]  I. Azuma,et al.  Adjuvant activity of mycobacterial fractions. I. Purification and in vivo adjuvant activity of cell wall skeletons of Mycobacterium bovis BCG, Nocardia asteroides 131 and Corynebacterium diphtheriae PW8. , 1975, Biken journal.