Platform technology to deliver prophylactic molecules orally: an example using the Class A select agent Yersinia...

Area of Science:

• Microbiology
• Immunology
• Vaccinology

Background:

• Lactic acid bacteria (LAB) are safe mucosal delivery vehicles.
• Previous work showed lipid-modified OspA in L. plantarum modulates Lyme disease vaccine response.
• This study explores LAB as a platform for vaccines against other pathogens, focusing on Yersinia pestis.

Purpose of the Study:

• To investigate the potential of L. plantarum as a platform for Yersinia pestis vaccines.
• To determine the immunogen localization within the LAB delivery vehicle.
• To evaluate the mucosal and systemic immune responses induced by the engineered LAB.

Main Methods:

• Cloning of Yersinia pestis LcrV antigen with a B. burgdorferi OspA signal sequence.
• Biochemistry and immunology techniques to assess antigen localization and immune responses.
• Animal studies (mice) to evaluate antibody titers and cytokine production.

Main Results:

• Only LcrV cloned downstream of the OspA signal sequence ((ss)LcrV) localized to the peptidoglycan layer of L. plantarum.
• Mice receiving L. plantarum expressing (ss)LcrV showed significant IgG and IgA antibody titers in systemic and mucosal sites (lungs, vagina).
• (ss)LcrV induced pro-inflammatory (TNFα, IL-12, IFNγ, IL-6) and anti-inflammatory (IL-10) cytokines, suggesting Th1/Th2 immune polarization.

Conclusions:

• L. plantarum expressing (ss)LcrV is effective in inducing both mucosal and systemic immunity against Yersinia pestis.
• The engineered LAB system demonstrates potential as a platform technology for developing oral vaccines against various diseases.
• Antigen modification and delivery vehicle integration are crucial for effective vaccine development using LAB.