Long-lasting immune response induced by recombinant bacillus Calmette-Guérin (BCG) secretion system

N Wada1, N Ohara, M Kameoka

  • 1School of Dentistry, Nagasaki University, Nagasaki City, Japan.

Insights

Recombinant bacillus Calmette-Guérin (rBCG) effectively secreted large amounts of a human immunodeficiency virus type 1 (HIV-1) epitope. This rBCG vaccine candidate induced long-lasting antibody production in mice, showing potential for future immunotherapies.

Area of Science:

  • Biochemistry
  • Immunology
  • Vaccine Development

Background:

  • The development of effective vaccine delivery systems is crucial for combating infectious diseases.
  • Recombinant bacillus Calmette-Guérin (rBCG) offers a promising platform for antigen delivery due to its established safety profile and immunomodulatory properties.
  • Utilizing extracellular antigens can enhance the immunogenicity of recombinant vaccines.

Purpose of the Study:

  • To characterize the rBCG secretion system for extracellular alpha antigen of Mycobacterium kansasii (alpha-K).
  • To evaluate the feasibility of secreting a fused antigen, specifically a human immunodeficiency virus type 1 (HIV-1) p17gag B cell epitope, using this system.
  • To assess the immunogenicity and durability of the antibody response generated by the engineered rBCG in a preclinical model.

Main Methods:

  • Biochemical and immunological characterization of the rBCG secretion system.
  • Construction of a fusion protein: HIV-1 p17gag epitope linked to alpha-K.
  • Inoculation of mice with the recombinant rBCG and subsequent measurement of antibody titers against the epitope.

Main Results:

  • The rBCG secretion system demonstrated efficient secretion of the alpha-K antigen.
  • Extremely large quantities of the fused HIV-1 p17gag epitope were secreted by the recombinant rBCG.
  • A significant proportion of mice (3 out of 7) developed high antibody titers against the HIV-1 epitope.
  • The antibody response was long-lasting, persisting for over 14 months post-inoculation.

Conclusions:

  • The characterized rBCG secretion system is highly effective for producing and secreting foreign antigens.
  • The fusion of an HIV-1 epitope to alpha-K resulted in robust and durable humoral immunity in a mouse model.
  • This study validates rBCG as a potent delivery vehicle for vaccine candidates, particularly for eliciting sustained antibody responses.

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