Background
Neisseria gonorrhoeae (Ng) infections represent an urgent global public health threat characterized by rising antimicrobial resistance and significant unmet medical needs. While real-world evidence shows that certain meningococcal B (Nm) OMV vaccines provide cross-protection against gonorrhea due to high antigen homology, no dedicated gonorrhea vaccine currently exists. Previous attempts using Ng-derived OMV platforms have faced challenges, including the pathogen’s inherent immune evasion mechanisms. These limitations underscore the need for a next-generation OMV approach that bypasses Ng-specific immune suppression.
Methods
DX-107 is a genetically engineered vaccine candidate that utilizes a Neisseria meningitidis (Nm) OMV chassis to deliver specific Ng antigens. This design leverages a non-suppressive, IND-approved OMV platform that is further modified through synthetic biology to enhance safety and immunogenicity. Genetic engineering is employed to attenuate OMV reactogenicity and achieve hyper-vesiculation for increased production efficiency. The candidate features the surface overexpression of key Ng protective antigens. Preclinical evaluations included monocyte activation tests (MAT) to assess innate immune activation and in vivo studies to evaluate antigen-specific antibody responses were conducted.
Results
DX-107 demonstrated a significant reduction in reactogenicity compared to wild-type OMVs in MAT assays, indicating an improved safety profile. Immunogenicity studies confirmed that the surface display of engineered Ng antigens elicited robust antibody responses and conferred protection against vaginal colonization in animal models. Furthermore, the platform showed high manufacturing potential, with strain engineering leading to a substantial increase in OMV yield compared to non-engineered parental strains. These results establish initial proof-of-concept for the candidate across the dimensions of safety, engineering precision, and scalability.
Conclusions
DX-107 represents a next-generation OMV vaccine candidate that addresses the historical hurdles of gonorrhea vaccine development by employing a heterologous OMV chassis. DX-107 provides a promising and scalable strategy to combat the global gonorrhea issue and the growing challenge of antimicrobial resistance.