Neisseria gonorrhoeae is strictly a human pathogen that causes the sexually transmitted infection termed gonorrhea, responsible for more than 100 million new cases worldwide each year. Due to the global emergence of antibiotic resistance against N. gonorrhoeae, the CDC listed the bacteria as an urgent threat to public health. Currently no vaccines are available. The goal of this proposal is to investigate the immunogenicity of a highly novel whole-cell based inactivated Neisseria gonorrhoeae vaccine. This vaccine consists of inactivated whole-cell gonococci spray dried and encapsulated into a biodegradable microparticles that can then be loaded into a microneedle skin patch for transdermal delivery. The advantages of using formalin-fixed whole-cell gonococci is that all immunogenic epitopes are protected and preserved from degradation and the spherical shape particles are biological mimics of gonococci, therefore when presented to the immune system, leads to heightened immunological response. Therefore, we propose the following: 1- Determine the optimal dose of antigen encapsulation into particles for further loading into biodegradable microneedles with the addition of adjuvants, assess effective antigen presentation by dendritic cells and T cell proliferation, and assess the expression of death receptor CD95 (Fas) on APCs; 2- Determine correlates of protection in mice immunized transdermally by measure of antibody titers and antigen-specific CD4/CD8 T lymphocytes in spleen and lymph nodes of vaccinated mice. Additionally, serum bactericidal activity and cross protection of elicited antibodies against live N. gonorrhoeae using the parent strain F62 as well as other clinical gonococcal isolates will be conducted. Based on the in vivo results of the optimized novel gonococcal particulate vaccine formulation and the pilot immunization studies, in subsequent follow up research projects, we will conduct a detailed mice immunization challenge study in collaboration with Dr. Ann Jerse, from the Uniformed Services University of the Health Sciences, Department of Defense, in Maryland, to test the ability of this novel gonococcal vaccine, delivered by biodegradable microneedle skin patch, to confer protection in a mice lower genital tract infection model. She will assist in carrying out studies such as chemokine analysis, RNA gene expression, cytology, antimicrobial peptides and tissue cloning.

Public Health Relevance

There is a dire need for vaccine against gonorrhea due to the high burden of gonorrheal disease combined with the emergence of antibiotic resistant gonococcal strains. This proposal harnesses the power of nanotechnology-based vaccine formulations that enhance immune responses to investigate a novel whole- cell based gonorrhea particulate vaccine.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
1R15AI133473-01A1
Application #
9590798
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Vincent, Leah Rebecca
Project Start
2018-07-20
Project End
2021-06-30
Budget Start
2018-07-20
Budget End
2021-06-30
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Mercer University Macon
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
065365041
City
Macon
State
GA
Country
United States
Zip Code
31207