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A Scalable Manufacturing Approach to Single Dose Vaccination against HPV.

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 Q?, to enhance their immunogenicity. The HPV-Q? 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-Q? 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-Q? 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 Q? technology is highly adaptable, allowing the production of vaccine candidates and their delivery devices for multiple strains or types of viruses.

SUBMITTER: Shao S

PROVIDER: S-EPMC7835769 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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A Scalable Manufacturing Approach to Single Dose Vaccination against HPV.

Shao Shuai S A Ortega-Rivera Oscar O Ray Sayoni S K Pokorski Jonathan J F Steinmetz Nicole N

Vaccines 20210119 1

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 prote ...[more]

PMID: 33478147

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Project description:BACKGROUND:Although guidelines for prophylactic human papillomavirus (HPV) vaccination recommend two doses for girls ages 9-14?years, several studies have demonstrated similar protection with one dose. Our objective was to evaluate the long-term health and economic impacts of routine one-dose HPV vaccination compared to (1) no vaccination and (2) two-dose HPV vaccination in a low-income country. METHODS:We used a three-tiered hybrid modeling approach that captured HPV transmission, cervical carcinogenesis, and population demographics to project long-term health and economic outcomes associated with one-dose HPV vaccination (assuming 80% efficacy against HPV-16/18 infections under three waning scenarios) and two-dose HPV vaccination (assuming 100% efficacy over the lifetime) in Uganda. Costs included the vaccine program (dosage and delivery) costs over a 10-year period and cervical cancer costs over the lifetimes of the current population of Ugandan women. Health outcomes included number of cervical cancer cases and disability-adjusted life years (DALYs). Incremental cost-effectiveness ratios (i.e., cost per DALY averted) were calculated and compared against the Ugandan per-capita gross domestic product. RESULTS:Routine one-dose HPV vaccination of 9-year-old girls required substantial upfront investment but was cost-saving compared to no vaccination when accounting for the cost-offsets from future cancers averted. Forty years after initiating routine vaccination and depending on assumptions of vaccine waning, one-dose HPV vaccination with equivalent coverage (70%) averted 15-16% of cervical cancer cases versus 21% with two-dose vaccination but required only half the upfront economic investment. Vaccination with two doses had an attractive cost-effectiveness profile except if one-dose vaccination enabled higher coverage (90% vs. 70%) and did not wane. CONCLUSIONS:One-dose HPV vaccination resulted in cost-savings compared to no vaccination and could be cost-effective compared to two-dose vaccination if protection is longstanding and higher coverage can be achieved.

Project description:BackgroundThe recent World Health Organization recommendation supporting single-dose of HPV vaccine will significantly reduce programmatic cost, mitigate the supply shortage, and simplify logistics, thus allowing more low- and middle-income countries to introduce the vaccine. From a programmatic perspective the durability of protection offered by a single-dose will be a key consideration. The primary objectives of the present study were to determine whether recipients of a single-dose of quadrivalent HPV vaccine had sustained immune response against targeted HPV types (HPV 6,11,16,18) at 10 years post-vaccination and whether this response was superior to the natural antibody titres observed in unvaccinated women.MethodsParticipants received at age 10-18 years either one, two or three doses of the quadrivalent HPV vaccine. Serology samples were obtained at different timepoints up to 10 years after vaccination from a convenience sample of vaccinated participants and from age-matched unvaccinated women at one timepoint. The evolution of the binding and neutralizing antibody response was presented by dose received. 10-year durability of immune responses induced by a single-dose was compared to that after three doses of the vaccine and in unvaccinated married women.ResultsThe dynamics of antibody response among the single-dose recipients observed over 120 months show stabilized levels 18 months after vaccination for all four HPV types. Although the HPV type-specific (binding or neutralizing) antibody titres after a single-dose were significantly inferior to those after three doses of the vaccine (lower bounds of GMT ratios < 0.5), they were all significantly higher than those observed in unvaccinated women following natural infections (GMT ratios: 2.05 to 4.04-fold higher). The results correlate well with the high vaccine efficacy of single-dose against persistent HPV 16/18 infections reported by us earlier at 10-years post-vaccination.ConclusionOur study demonstrates the high and durable immune response in single-dose recipients of HPV vaccine at 10-years post vaccination.

Dataset Information

A Scalable Manufacturing Approach to Single Dose Vaccination against HPV.

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A Scalable Manufacturing Approach to Single Dose Vaccination against HPV.

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