Novel Whole-Cell Inactivated Neisseria Gonorrhoeae Microparticles as Vaccine Formulation in Microneedle-Based Transdermal Immunization

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.

Stable Immune Response Induced by Intradermal DNA Vaccination by a Novel Needleless Pyro-Drive Jet Injector

“…Thus, a study comparing the vaccination efficacy of intramuscular and intradermal administration was conducted and reported [23]. Additionally, an intradermal vaccine as well as novel delivery techniques, including micro-needle devices, have been developed and investigated to improve vaccination therapy effectiveness [24–31]. One of the obstacles facing intradermal vaccine development is the technical difficulty associated with its delivery in animal models; as the skin thicknesses of rats and mice are approximately 2 and 0.8 mm, respectively, they are ideal candidates for initial experimentation [32].…”

<p>Technology update: dissolvable microneedle patches for vaccine delivery</p>

“…Other studies looked at DMN-based immunization against Neisseria gonorrhoeae and Staphylococcus aureus , with promising results. In the first case, DMN-immunization of mice with whole-cell gonococci encapsulated in albumin microparticles led to higher antibody levels than an SC injection of the vaccine suspension 63. Similarly, Liu and co-workers reported extended antigen retention in mice, higher antibody levels and stronger protection against challenge using DMN for vaccination against S. aureus , in comparison with IM vaccination 71…”

Better Adjuvants for Better Vaccines: Progress in Adjuvant Delivery Systems, Modifications, and Adjuvant–Antigen Codelivery

“…For example, some whole-cell inactivated vaccines have strong adjuvant effects due to their intact pathogen structure; however, their safety is questionable. Thus, using an antigen delivery system ensures slow release of antigens and helps in achieving good effectiveness and safety by prolonged stimulation of immune response from small antigen doses [106].…”