Lactobacilli Expressing Broadly Neutralizing Nanobodies against HIV-1 as Potential Vectors for HIV-1 Prophylaxis?

Area of Science:

• Immunology
• Microbiology
• Virology

Background:

• Broadly neutralizing antibodies (bnAbs) show promise for HIV-1 prevention but face challenges in achieving sustained levels for sexual transmission.
• The acidic vaginal environment poses difficulties for traditional passive antibody administration against HIV-1.

Purpose of the Study:

• To develop a novel delivery system for broadly neutralizing nanobodies (bn VHH) against HIV-1 using Lactobacillus.
• To evaluate the efficacy and stability of bn VHH expressed by Lactobacillus in the vaginal environment.

Main Methods:

• Engineered Lactobacillus rhamnosus DSM14870 to express VHHA6 nanobodies in soluble and cell-wall-anchored forms.
• Tested the neutralizing activity of VHHA6 against relevant HIV-1 strains in vitro.
• Assessed the activity of VHHA6 at acidic pH, mimicking vaginal conditions.

Main Results:

• Recombinant VHHA6 expressed in E. coli protected humanized mice from mucosal HIV-1 infection.
• Both soluble and cell-wall-anchored VHHA6 expressed in Lactobacillus neutralized diverse primary HIV-1 strains.
• VHHA6 retained activity in acidic conditions, indicating stability in the vaginal environment.

Conclusions:

• Lactobacillus-expressed bn VHH represent a promising platform for passive immunization against HIV-1.
• This approach could be particularly beneficial for high-risk women, offering a stable and effective method for preventing sexual HIV-1 transmission.