CHO expressed recombinant human lactoferrin as an adjuvant for BCG

Area of Science:

• Immunology
• Vaccinology
• Infectious Diseases

Background:

• Tuberculosis (TB) remains a significant global health challenge, with the current Bacillus Calmette Guerin (BCG) vaccine offering limited efficacy against adult pulmonary TB.
• Lactoferrin (LF), an iron-binding protein, possesses immune-modulatory properties and has demonstrated adjuvant activity, suggesting potential to enhance vaccine effectiveness.
• Progressive TB is characterized by severe pulmonary pathology driven by inflammation and immune reactivity.

Purpose of the Study:

• To investigate the potential of Chinese hamster ovary (CHO)-expressed recombinant human lactoferrin (rHLF) as an adjuvant to boost BCG vaccine efficacy.
• To evaluate the impact of rHLF supplementation on delaying early pulmonary pathology following Mycobacterium tuberculosis (MTB) infection.
• To analyze the immunomodulatory effects of rHLF in conjunction with the BCG vaccine.

Main Methods:

• C57BL/6 mice were immunized with BCG, BCG admixed with rHLF, or BCG with bovine lactoferrin (bLF) as a control, or left unvaccinated.
• Mice were subsequently challenged with aerosolized Erdman strain MTB.
• Bacterial load, lung pathology, cytokine profiles (IFN-γ, IL-6, GM-CSF, IL-10), and T cell responses were assessed post-infection.

Main Results:

• All vaccinated groups exhibited reduced organ bacterial loads compared to unvaccinated controls up to 19 weeks post-infection.
• BCG vaccination supplemented with either rHLF or bLF demonstrated a modest decrease in lung pathology over time compared to BCG alone.
• BCG/rHLF vaccination enhanced splenic recall responses, increasing IFN-γ, IL-6, and GM-CSF production, and decreased IL-10 production by antigen-presenting cells.

Conclusions:

• Addition of rHLF to the BCG vaccine can enhance vaccine efficacy and reduce lung pathology in a mouse model of TB.
• rHLF appears to modulate host immune responses, potentially mitigating hypersensitive reactions that contribute to TB pathology.
• rHLF shows promise as an adjuvant for improving the effectiveness of the BCG vaccine against Mycobacterium tuberculosis.