Abstract
Despite the successes provided by vaccination, many challenges still exist with respect to controlling new and re-emerging infectious diseases. Innovative vaccine platforms composed of adaptable adjuvants able to appropriately modulate immune responses, induce long-lived immunity in a single dose, and deliver immunogens in a safe and stable manner via multiple routes of administration are needed. This work describes the development of a novel biodegradable polyanhydride nanoparticle-based vaccine platform administered as a single intranasal dose that induced long-lived protective immunity against respiratory disease caused by Yesinia pestis, the causative agent of pneumonic plague. Relative to the responses induced by the recombinant protein F1-V alone and MPLA-adjuvanted F1-V, the nanoparticle-based vaccination regimen induced an immune response that was characterized by high titer and high avidity IgG1 anti-F1-V antibody that persisted for at least 23 weeks post-vaccination. After challenge, no Y. pestis were recovered from the lungs, livers, or spleens of mice vaccinated with the nanoparticle-based formulation and histopathological appearance of lung, liver, and splenic tissues from these mice post-vaccination was remarkably similar to uninfected control mice.
Highlights
Natural infections with pathogens stimulate protective and lasting antibody responses because they induce affinity maturation of B cells, a process by which B cells produce antibodies with an increased affinity for antigen during the course of an immune response [1]
The results presented demonstrate that encapsulation of F1-V into polyanhydride nanoparticles administered as a single intranasal dose successfully induced long-term protection against Y. pestis that correlated with a high titer, high avidity F1-Vspecific antibody response
Polyanhydride Nanoparticle Design We have previously shown that encapsulation of F1-V into amphiphilic polyanhydride particles based on 1,6-bis(p-carboxyphenoxy)hexane (CPH) and 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG) successfully preserved the antigenicity of F1-V upon release [26]
Summary
Natural infections with pathogens stimulate protective and lasting antibody responses because they induce affinity maturation of B cells, a process by which B cells produce antibodies with an increased affinity for antigen during the course of an immune response [1]. Development of single-dose, tailored nano-adjuvant platforms will provide an effective means to induce protective immunity, but will allow production of cost-effective vaccines that can reduce the need for multiple injections and result in greater patient compliance. These novel technologies will obviate the need for hypodermic needles and professionals to administer the vaccine. Implementation of vaccine delivery systems based on biodegradable polymers offers significant advantages for immunization regimens
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