Project 1 - VesiVax®-adjuvanted cocktail vaccine formulation against Neisseria gonorrhoeae (CIIG)

Project Summary The purpose of Project 1 is to facilitate the development of vaccines as a medical countermeasure for the highly antibiotic resistant bacterial pathogen Neisseria gonorrhoeae (Ng). Disease caused by Ng (gonorrhea) is considered an urgent public health threat by the Centers for Disease Control and Prevention due to dramatically increasing rates of disease, and extensive, rapidly developing multi-drug resistance. Development and assessment of vaccines to prevent gonorrhea are complicated by antigenic diversity, similar to vaccines for prevention of serogroup B meningococcal (MenB) disease, and by the lack of immunologic protection afforded by natural infection. Observational studies have provided precedence for successful vaccine development in that populations immunized with MenB outer membrane vesicle (OMV) vaccines experienced decreased incidence of gonorrhea. While estimates of the short-term effectiveness of a licensed MenB vaccine that contains OMV (4CMenB) for prevention of gonorrhea range from 30% to 40%, an optimized N. gonorrhoeae vaccine with high durable efficacy and broad coverage against diverse strains is urgently needed. The principal goal of Project 1 is to advance and support the transition to clinical development of an efficacious Ng vaccine composed of: (i) a novel genetically modified N. meningitidis (Nm) ΔABRSL OMV, (ii) synergetic recombinant Ng antigens and (iii) optimal immunostimulatory adjuvant molecules (IAMs) in the VesiVax® liposome platform. We will select the optimal VesiVax®-IAMs-OMV from a panel of five IAMs through in vivo immune characterizations and efficacy studies (Aim 1). Concurrently, we will select the optimal combination of recombinant Ng antigens, by evaluating VesiVax®-IAM-Ng antigen formulations with a panel of five Ng antigens identified by immunoproteomics, using in vivo immune characterizations and efficacy studies (Aim 2). Aims 1 and 2 will be completed by the end of Years 1 and 2, respectively. Optimal VesiVax®-IAM-OMV and VesiVax®-IAM-Ng will then be combined and tested to down-select the least complex multi-component vaccine with the highest efficacy and cross-protective effects (Aim 3). The optimal VesiVax® Ng vaccine formulation will be further characterized to establish (i) duration of protection, (ii) efficacy in an ascending model and (iii) efficacy in a Ng/Chlamydia co-infection model. Scale-up development activities will commence, with development lots produced and preliminary stability studies performed starting in Year 4 (Aim 4).