Abstract
Human papillomavirus (HPV) is a globally prevalent sexually-transmitted pathogen, responsible for most cases of cervical cancer. HPV vaccination rates remain suboptimal, partly due to the need for multiple doses, leading to a lack of compliance and incomplete protection. To address the drawbacks of current HPV vaccines, we used a scalable manufacturing process to prepare implantable polymer–protein blends for single-administration with sustained delivery. Peptide epitopes from HPV16 capsid protein L2 were conjugated to the virus-like particles derived from bacteriophage Qβ, to enhance their immunogenicity. The HPV-Qβ particles were then encapsulated into poly(lactic-co-glycolic acid) (PLGA) implants, using a benchtop melt-processing system. The implants facilitated the slow and sustained release of HPV-Qβ particles without the loss of nanoparticle integrity, during high temperature melt processing. Mice vaccinated with the implants generated IgG titers comparable to the traditional soluble injections and achieved protection in a pseudovirus neutralization assay. HPV-Qβ implants offer a new vaccination platform; because the melt-processing is so versatile, the technology offers the opportunity for massive upscale into any geometric form factor. Notably, microneedle patches would allow for self-administration in the absence of a healthcare professional, within the developing world. The Qβ technology is highly adaptable, allowing the production of vaccine candidates and their delivery devices for multiple strains or types of viruses.
Highlights
Human papillomavirus (HPV) is a globally-prevalent pathogen and the most common sexually-transmitted infection in the USA [1]
The HPV16 epitope L217–31 is ideal for the development of an effective HPV vaccine because it is highly conserved among diverse HPV isolates [15,16,17]
The peptides were conjugated to the surface of the virus-like particles (VLPs) derived from bacteriophage Qβ in a two-step procedure, where a bifunctional PEG was first conjugated via the NHS-chemistry to surface amines of Qβ
Summary
Human papillomavirus (HPV) is a globally-prevalent pathogen and the most common sexually-transmitted infection in the USA [1]. Despite the protection offered by the HPV vaccine, only 53.7% of girls and 48.7% of boys in the US were vaccinated against HPV in 2019 [7]. The poor quality of public health services in many developing countries means the vaccination rates are even worse, even though HPV infections are more prevalent [9]. Based on 2011 data, only 70.7% of girls and 28.1% of boys who receive the first dose go on to complete the course [8,10]. Another considerable logistical and fiscal barrier is the cold chain requirement for HPV vaccines, making it untenable to distribute life-saving vaccines in resource-poor areas of the world. Innovating vaccine platforms and delivery devices to break cold chain limitations is an excellent solution to safeguard potent vaccination for both wealthy and lower-income countries
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