Bacterium-like particles derived from the respiratory commensal bacteria corynebacterium pseudodiphtheriticum 090104 as a promising mucosal adjuvant

Abstract

Corynebacterium pseudodiphtheriticum is a Gram-positive bacterium that is part of the nasopharyngeal microbiota. Cp was shown to prevent the colonization of the respiratory mucosa by pathogenic bacteria including Streptococcus pneumoniae (Sp). We recently demonstrated that C. pseudodiphtheriticum 090104 (Cp), when nasally administered to mice; differentially modulated the respiratory immune responses triggered by TLR2 and improved the resistance to pneumococcal pneumonia. We also reported that bacterium-like particles derived from Cp (BPCp) had the ability to modulate the innate respiratory immunity. These results allowed us to hypothesize that Cp or BPCp could be used as mucosal adjuvants to enhance the respiratory adaptive immunity. In this work, infant Swiss-albino mice were nasally immunized with 6.25 pg of Pneumovax23® vaccine (PV), PV plus Cp (108 CFU) or PV plus BPCp at days 0, 14 and 28. Seven days after the last immunization samples of bronco-alveolar lavages (BAL) and serum were collected for specific antibodies determinations. In addition, immunized mice were challenged with Sp serotypes 6B or 19F (106 CFU) and the resistance to the infection was evaluated 2 days after the challenge. Mice in the PV+Cp and PV+BPCp groups had significantly higher levels of BAL anti-Sp IgG and IgA (p<0.01) as well as serum IgG and IgM (p<0.01) in comparison with mice immunized only with PV. Of note, the PV+Cp immunization was more efficient than PV+BPCp to improve respiratory and serum antibodies levels. PV+Cp and PV+BPCp mice had lower Sp counts in lungs than controls, as well as negative hemocultures. In addition, PV+Cp and PV+BPCp groups had higher levels of BAL and serum TNF-α, IFN-γ and IL-4 (p<0.05) than controls after Sp infection. Again, Cp was more efficient than BPCp to induce protection against Sp 6B and 19F. The results show that both Cp and BPCp are promising mucosal adjuvants for the development of nasal vaccines to combat respiratory infections.