Abstract
Neisseria gonorrhoeae is a strict human pathogen responsible for more than 100 million new sexually transmitted infections worldwide each year. Due to the global emergence of antibiotic resistance, the Center for Disease control (CDC) recently listed N. gonorrhoeae as an urgent threat to public health. No vaccine is available in spite of the huge disease burden and the possibility of untreatable gonorrhea. The aim of this study is to investigate the immunogenicity of a novel whole-cell-based inactivated gonococcal microparticle vaccine formulation loaded in dissolvable microneedles for transdermal administration. The nanotechnology-based vaccine formulation consists of inactivated whole-cell gonococci strain CDC-F62, spray dried and encapsulated into biodegradable cross-linked albumin matrix with sustained slow antigen release. The dry vaccine nanoparticles were then loaded in a dissolvable microneedle skin patch for transdermal delivery. The efficacy of the whole-cell microparticles vaccine formulation loaded in microneedles was assessed in vitro using dendritic cells and macrophages as well as in vivo mouse model. Antibody titers were measured using an enzyme immunosorbent assay (ELISA) and antigen-specific T lymphocytes were assessed in spleens and lymph nodes. Here we report that whole-cell-based gonococcal microparticle vaccine loaded in dissolvable microneedles for transdermal administration induced significant increase in antigen-specific IgG antibody titers and antigen-specific CD4 and CD8 T lymphocytes in mice compared to gonococcal antigens in solution or empty microneedles. Significant increase in antigen-specific IgG antibody levels was observed at the end of week 2 in groups that received the vaccine compared to the group receiving empty nanoparticles. The advantages of using formalin-fixed whole-cell gonococci that all immunogenic epitopes are covered and preserved from degradation. The spherical shaped micro and nanoparticles are biological mimics of gonococci, therefore present to the immune system as invaders but without the ability to suppress adaptive immunity. In conclusion, the transdermal delivery of microparticles vaccine via a microneedle patch was shown to be an effective system for vaccine delivery. The novel gonorrhea nanovaccine is cheap to produce in a stable dry powder and can be delivered in microneedle skin patch obviating the need for needle use or the cold chain.
Highlights
Neisseria gonorrhoeae is strictly a human pathogen that causes sexually transmitted infection.The disease state termed gonorrhea accounts for >100 million cases worldwide each year
We developed a novel nanotechnology-based vaccine formulation consisting of formalin fixed whole-cell N. gonorrhoeae as the vaccine antigen encapsulated in biodegradable microparticles loaded in microneedles for transdermal administration
The novel particulate gonorrhea vaccine formulation is delivered transdermally using biodegradable microneedles “skin patch”. This novel gonorrhea vaccine skin patch is tested in vivo using mouse microneedles “skin patch”. This novel gonorrhea vaccine skin patch is tested in vivo using mouse model and data demonstrated that transdermal vaccine delivery induced significantly higher levels model and data demonstrated that transdermal vaccine delivery induced significantly higher levels of of humoral and adaptive immune responses i.e., antigen-specific serum IgG and antigen-specific CD4 humoral and adaptive immune responses i.e., antigen-specific serum IgG and antigen-specific CD4 and CD8 T lymphocytes
Summary
Neisseria gonorrhoeae is strictly a human pathogen that causes sexually transmitted infection.The disease state termed gonorrhea accounts for >100 million cases worldwide each year. The gonococcus can survive extracellularly and intracellularly, in both environments, the bacteria must adapt to pressures exerted by the host [3,4]. There were over 460,000 reported cases in the US in 2016, and several more that are not reported It is much more common in Africa and other developing nations [6]. The main reason to warrant the development of a gonococcal vaccine is the emergence of antibiotic-resistant GC, which has led to a rapid increase in the prevalence of the infections since 2012 [8]. With the development of antibiotic-resistant strains of N. gonorrhoeae, the Food and Drugs Administration (FDA) and CDC have listed the research and development of a vaccine against gonorrhea as a high priority
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