An official website of the United States government
Background Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States. HPV can cause genital warts and multiple types of cancers in females. HPV vaccination is recommended to youth age 11 or 12 years before sexual initiation to prevent onset of HPV-related diseases. For females who have not been vaccinated previously, catch-up vaccines are recommended through age 26. The extent to which catch-up vaccines are beneficial in terms of disease prevention and cost-effectiveness is questionable given that some women may have been exposed to HPV before receiving the catch-up vaccination. This study aims to examine whether the cutoff age of catch-up vaccination should be determined based on an individual woman’s risk characteristic instead of a one-size-fits-all age 26. Methods We developed a microsimulation model to evaluate multiple clinical outcomes of HPV vaccination for different women based on a number of personal attributes. We modeled the impact of HPV vaccination at different ages on every woman and tracked her course of life to estimate the clinical outcomes that resulted from receiving vaccines. As the simulation model is risk stratified, we used extreme gradient boosting to build an HPV risk model estimating every woman’s dynamic HPV risk over time for the lifetime simulation model. Results Our study shows that catch-up vaccines still benefit all women after age 26 from the perspective of clinical outcomes. Women facing high risk of HPV infection are expected to gain more health benefits compared with women with low HPV risk. Conclusions From a cancer prevention perspective, this study suggests that the catch-up vaccine after age 26 should be deliberately considered.
more »
« less
A Scalable Manufacturing Approach to Single Dose Vaccination against HPV
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.
more »
« less
- Award ID(s):
- 2027668
- PAR ID:
- 10288986
- Date Published:
- Journal Name:
- Vaccines
- Volume:
- 9
- Issue:
- 1
- ISSN:
- 2076-393X
- Page Range / eLocation ID:
- 66
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Abstract Drug delivery systems have renewed attention in recent years to achieve targeted delivery while decreasing toxic side effects. However, there are many factors that prevent optimal administration of drug delivery particles. For instance, protein corona formation and aggregation both decrease the circulation half‐life of drug delivery particles, leading to sequestration to the liver and spleen. Therefore, optimal surface modifications are needed to decrease protein corona formation and avoid aggregation. In this work, polystyrene particles were modified with multi‐arm and linear polyethylene glycol (PEG) to determine their aggregation profiles and protein corona formation. Multi‐arm PEGs were found to aggregate more than linear PEGs, due to the change in zeta potential from unreacted end groups, which may lead to shorter circulation half‐lives. Furthermore, the protein corona formation and composition were studied after different washing procedures, highlighting the importance of studying protein corona formation with undiluted blood plasma.more » « less
-
Plant virus-like particles (VLPs) are biocompatible, non-infectious nanomaterials with promising applications as immunotherapeutics and vaccines. However, slow-release VLP formulations are needed to achieve long-term efficacy without repeated administration. VLP hydrogels allow the encapsulation and sustained delivery of VLPs, but the particles must covalently bind the hydrogel polymers to avoid premature loss. This has been achieved so far by in situ VLP polymerization, which requires high viral concentrations (5–10 mg/mL, 0.5–1 wt%) to form stable hybrid VLP–hydrogel networks and this complicates scalability and clinical translation. Here, we developed a novel swell-and-click method that led to successful VLP scaffold formation regardless of the viral load used. As a result, VLP-functionalized hydrogels were fabricated with viral concentrations as low as 0.1–1 mg/mL (0.01–0.1 % wt%) without compromising the scaffold stability on the process. The hydrogels incorporate VLPs during swelling, followed by copper-free click chemistry reactions that bind the particles covalently to the polymer. The swell-and-click method also resulted in more than a two-fold enhancement in VLP uptake into the hydrogels and it provides a means of combined burst release and prolonged sustained release, desired traits for cancer immunotherapy treatment. The present work introduces a novel methodology for the design of VLP-based hydrogels, which could facilitate the scalability of the fabrication process and move a significant step forward towards clinical translation of long-term VLP vaccination in cancer disease.more » « less
-
BackgroundThe prevalence of human papillomavirus (HPV) and its related cancers is a major global concern. In the United States, routine HPV vaccination is recommended for youth aged 11 or 12 years. Despite HPV being the most common sexually transmitted infection and the vaccine’s proven efficacy, the vaccination rate among US youth remains below the recommended 80% completion rate. Mobile health (mHealth) interventions have demonstrated promise in improving health. Examining and synthesizing the current evidence about the impact of mHealth interventions on vaccination coverage in youth and intervention characteristics could guide future mHealth interventions aimed at mitigating the vaccination gap and disease burden. ObjectiveThis study aims to conduct a systematic review to assess the effectiveness of mHealth interventions on parental intent to vaccinate youth against HPV and youth’s vaccine uptake. MethodsWe searched empirical papers through databases including Google Scholar, PubMed, CINAHL, PsycINFO, and Cochrane Library. The inclusion criteria were the following: (1) published between January 2011 and December 2022; (2) using mHealth aimed to improve HPV vaccination rate; (3) targeted unvaccinated youth or their parents; and (4) measured HPV-related knowledge, vaccination intention, or vaccine uptake. Overall, 3 researchers screened and appraised the quality of the eligible papers using the Melnyk Levels of Evidence and the Cochrane Grading of Recommendations Assessment, Development, and Evaluation methodology. Disagreements in search results and result interpretation were resolved through consensus. ResultsOverall, 17 studies that met the inclusion criteria were included in the final review. Most studies were conducted in the United States (14/17, 82%), used a randomized controlled trial design (12/17, 71%), and adopted behavior change theories or a culture-centric approach (10/17, 59%). mHealth interventions included SMS text message reminders, motivational SMS text messages, computer-tailored or tablet-tailored interventions, smartphone apps, web-based tailored interventions, social media (Facebook) campaigns, digital videos, and digital storytelling interventions. Approximately 88% (15/17) of the mHealth interventions demonstrated positive effects on knowledge, intention, or behaviors related to HPV vaccination. Overall, 12% (2/17) reported limited or no intervention impact on vaccine uptake or vaccine series completion. Effective vaccine uptake was commonly seen in interventions based on behavior change theories and those that provided culturally relevant information. ConclusionsThis systematic review identified the impact of mHealth interventions among unvaccinated youth and their parents, which showed improvement in HPV-related knowledge, vaccination intention, or vaccine initiation. The interventions that incorporated theories and culture-centric approaches revealed the most promising results. Although these outcomes are encouraging, future studies are needed to investigate factors associated with the success of interventions using SMS text messaging or social media. More studies are also needed for a better understanding of the intervention elements that boost the responses of age-specific and ethnicity-specific populations.more » « less
-
The coat proteins (CPs) of single-stranded RNA bacteriophages (ssRNA phages) directly assemble around the genomic RNA (gRNA) to form a near-icosahedral capsid with a single maturation protein (Mat) that binds the gRNA and interacts with the retractile pilus during infection of the host. Understanding the assembly of ssRNA phages is essential for their use in biotechnology, such as RNA protection and delivery. Here, we present the complete gRNA model of the ssRNA phage Qβ, revealing that the 3′ untranslated region binds to the Mat and the 4127 nucleotides fold domain-by-domain, and is connected through long-range RNA–RNA interactions, such as kissing loops. Thirty-three operator-like RNA stem-loops are located and primarily interact with the asymmetric A/B CP-dimers, suggesting a pathway for the assembly of the virions. Additionally, we have discovered various forms of the virus-like particles (VLPs), including the canonical T = 3 icosahedral, larger T = 4 icosahedral, prolate, oblate forms, and a small prolate form elongated along the 3-fold axis. These particles are all produced during a normal infection, as well as when overexpressing the CPs. When overexpressing the shorter RNA fragments encoding only the CPs, we observed an increased percentage of the smaller VLPs, which may be sufficient to encapsidate a shorter RNA.more » « less
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.3390/vaccines9010066
