Protein glycans as vaccine antigens against Neisseria gonorrhoeae

Summary 

Neisseria gonorrhoeae, the causative agent of the sexually transmitted infection gonorrhoea, represents an emerging global health problem with increasing antibiotic resistance. Vaccine development is complicated by the fact that gonorrhoea infections fail to engender protective immunity. A successful vaccine against gonorrhoea should therefore include multiple antigens and induce a protective immune response beyond that generated through natural infections.

Identification of suitable vaccine targets remains a bottleneck and identification of conserved antigens through comparative genomics overlooks post-translational modifications. Here, we aim at providing proof-of-concept for protein glycans as important vaccine antigens against gonorrhoea. The glycoproteins identified in N. gonorrhoeae are mainly lipoproteins or transmembrane proteins localized in the periplasm or on the cell surface, and we have established that the attached glycans are antigenic and immunogenic.

We have interesting results that protein glycans are protecting the gonococci against bactericidal activity and indirect results that antibodies against these glycans might be bactericidal. We will confirm and validate these results in different strains and investigate the molecular mechanisms behind these observations by using a panel of mutant strains that express different glycans or glycoproteins. Recent studies have shown decreased rates of gonorrhea after vaccination with meningococcal outer membrane vesicle (OMV) vaccines, and we will identify the glycoproteins and attached glycans within these OMV vaccines.