Campylobacter jejuni (C. jejuni) is accountable for more than 400 million cases of
gastroenteritis each year and is listed as a high-priority gut pathogen by the World Health Organization (WHO). Although the acute
infection of C. jejuni (
campylobacteriosis) is commonly treated with
macrolides and
fluoroquinolones, the emergence of antibiotic resistance among C. jejuni warrants the need for an alternative approach to control
campylobacteriosis in humans. To this end,
vaccines remain a safe, effective, and widely accepted strategy for controlling emerging and
re-emerging infectious diseases. In search of a suitable
vaccine against
campylobacteriosis, recently, we demonstrated the potential of recombinant Haemolysin co-regulated
protein (Hcp) of C. jejuni
Type VI secretion system (T6SS) in imparting significant immune-protection against cecal colonization of C. jejuni; however, in the avian model. Since clinical features of human
campylobacteriosis are more complicated than the avians, we explored the potential of Hcp as a T6SS targeted
vaccine in a murine model as a more reliable and reproducible experimental host to study
vaccine-induced immune-protection against C. jejuni. Because C. jejuni primarily utilizes the mucosal route for host pathogenesis, we analyzed the immunogenicity of a mucosally deliverable bioengineered Lactic acid bacteria (LAB), Lactococcus lactis (L. lactis), expressing Hcp. Considering the role of Hcp in both structural (membrane-bound) and functional (effector
protein) exhibition of C. jejuni T6SS, a head-to-head comparison of two different forms of recombinant LAB vectors (cell wall anchored and secreted form of Hcp) were tested and assessed for the immune phenotypes of each modality in BALB/c mice.
RESULTS: We show that regardless of the Hcp
protein localization, mucosal delivery of bioengineered LAB vector expressing Hcp induced high-level production of
antigen-specific
neutralizing antibody (
sIgA) in the gut with the potential to reduce the cecal load of C. jejuni in mice.
CONCLUSION: Together with the non-commensal nature of L. lactis, short gut transit time in humans, and the ability to express the heterologous
protein in the gut, the present study highlights the benefits of bioengineered LAB vectors based mucosal
vaccine modality against C. jejuni without the risk of immunotolerance.