Potential cost-effectiveness of adjuvanted herpes zoster subunit vaccine for older adults in Hong Kong.

BACKGROUND: Adjuvanted herpes zoster (HZ) subunit vaccine is recommended for adults aged ≥50 years. This study aimed to investigate cost-effectiveness of HZ subunit vaccine for older adults at different age in Hong Kong. METHODS: A life-long Markov model was designed to simulate outcomes of four alternatives: Vaccination at model entry (age 50 years); deferring vaccination to 60 years; deferring vaccination to 70 years; and no vaccination. Outcome measures included direct cost, indirect cost, HZ and post-herpetic neuralgia incidences, quality-adjusted life years (QALYs) loss, and incremental cost per QALY saved (ICER). Model clinical inputs were derived from literature. HZ treatment costs were collected from a cohort of HZ patients (n = 218). One-way and probabilistic sensitivity analyses were performed. RESULTS: In base-case analysis, vaccination at 50 years showed highest QALYs saved and increment cost (0.00258; USD166), followed by deferring to 60 years (0.00215 QALYs saved; USD102) and deferring to 70 years (0.00134 QALYs; USD62) when comparing to no vaccination. ICERs of vaccination arms versus no vaccine (46,267-64,341 USD/QALY) were between 1-3 × gross domestic product (GPD) per capita in Hong Kong (USD43,530-USD130,590). One-way sensitivity analyses found vaccine cost to be the common and most influential parameter for ICER of each vaccination strategy to become <1 × GDP per capita. In probabilistic sensitivity analysis, vaccination at 50 years, deferring to 60 years and 70 years were accepted as cost-effective in 90% of time at willingness-to-pay (WTP) of 78,400 USD/QALY, 57,680 USD/QALY and 53,760 USD/QALY, respectively. CONCLUSIONS: Cost-effectiveness of each strategy is highly subject to the vaccine cost and WTP threshold per QALY saved.

Shingrix: The New Adjuvanted Recombinant Herpes Zoster Vaccine.

OBJECTIVES: To review the immunogenicity, efficacy, and safety of the herpes zoster subunit vaccine (HZ/su) for use in adult patients for the prevention of shingles. DATA SOURCES: A literature search through PubMed was conducted (June 2008 to October 2017) using the terms shingles vaccine and varicella zoster virus. References from retrieved articles and the prescribing information were also reviewed for any additional material. STUDY SELECTION/DATA EXTRACTION: The literature search was limited to human studies published in English. Randomized controlled, multicenter trials were reviewed and included to evaluate the safety and efficacy of HZ/su. Literature on the epidemiology and pathology of herpes zoster virus infections and recommendations from the Advisory Committee on Immunization Practices (ACIP) were also reviewed. DATA SYNTHESIS: HZ/su is a new adjuvanted recombinant vaccine approved by the Food and Drug Administration for the prevention of herpes zoster in adults 50 years of age and older. HZ/su significantly reduced the risk of developing herpes zoster by more than 90% as compared with placebo and displayed a comparable adverse effect profile. The most common local adverse events were injection site pain, redness, and swelling, and the most common systemic adverse events were myalgia, fatigue, and headache. The ACIP recommends the routine use of HZ/su as the preferred vaccine for the prevention of herpes zoster in immunocompetent adults 50 years of age and older. CONCLUSIONS: Based on published immunogenicity, efficacy, and safety data, as well as the recent recommendations by the ACIP, HZ/su should be included on both hospital and community pharmacy formularies and recommended to all immunocompetent patients older than 50 years to prevent herpes zoster.

A novel immunization approach for dengue infection based on conserved T cell epitopes formulated in calcium phosphate nanoparticles.

Dengue virus (DV) is the etiologic agent of dengue fever, the most significant mosquito-borne viral disease in humans. Most DV vaccine approaches are focused on generating antibody mediated responses; one such DV vaccine is approved for use in humans but its efficacy is limited. While it is clear that T cell responses play important role in DV infection and subsequent disease manifestations, fewer studies are aimed at developing vaccines that induce robust T cells responses. Potent T cell based vaccines require 2 critical components: the identification of specific T cell stimulating MHC associated peptides, and an optimized vaccine delivery vehicle capable of simultaneously delivering the antigens and any required adjuvants. We have previously identified and characterized DV specific HLA-A2 and -A24 binding DV serotypes conserved epitopes, and the feasibility of an epitope based vaccine for DV infection. In this study, we build on those previous studies and describe an investigational DV vaccine using T cell epitopes incorporated into a calcium phosphate nanoparticle (CaPNP) delivery system. This study presents a comprehensive analysis of functional immunogenicity of DV CaPNP/multipeptide formulations in vitro and in vivo and demonstrates the CaPNP/multipeptide vaccine is capable of inducing T cell responses against all 4 serotypes of DV. This synthetic vaccine is also cost effective, straightforward to manufacture, and stable at room temperature in a lyophilized form. This formulation may serve as an effective candidate DV vaccine that protects against all 4 serotypes as either a prophylactic or therapeutic vaccine.

Economic benefits for the family of inactivated subunit virosomal influenza vaccination of healthy children aged 3-14 years during the annual health examination in private paediatric offices.

Taking the results of a prospective cohort study by our group that evaluated the effectiveness of the inactivated subunit virosomal influenza vaccine (Inflexal V), Crucell-Berna) in the prevention of influenza-related diseases and the reduction of its negative economic consequences, the economic costs and benefits for the family of vaccinating a theoretical cohort of 1000 healthy children aged 3-14 years with no risk factors with one dose of vaccine during the yearly health examination were quantiified. The economic analysis was carried out from the family perspective and the time horizon of the study was established at 6 months. In the base case, the net present value was 21,551.62 euros (21.5 euros per vaccinated child), and the benefit-cost ratio was 2.15, meaning that 1.15 euros is saved per euro invested.

Recent progress in the development of plant derived vaccines.

Recombinant subunit vaccines have been with us for the last 30 years and they provide us with the unique opportunity to choose from the many available production systems that can be used for recombinant protein expression. Plants have become an attractive production platform for recombinant biopharmaceuticals and vaccines have been at the forefront of this new and expanding industry sector. The particular advantages of plant-based vaccines in terms of cost, safety and scalability are discussed in the light of recent successful clinical trials and the likely impact of plant systems on the vaccine industry is evaluated.

Plants as biofactories.

Cell substrates are a key component of successful vaccine development and throughout the last several decades there has been a dramatic increase in the types of cells available for vaccine production. Nevertheless, there is a continued demand for new and innovative approaches for vaccine development and manufacturing. Recent developments involving cells of insect and plant origin are attracting considerable scientific interest. Here we review vaccine antigen production in plant-based systems as was presented by Dr. Vidadi Yusibov of Fraunhofer USA Center for Molecular Biotechnology at the IABS International Scientific Workshop on NEW CELLS FOR NEW VACCINES II that was held in Wilmington, Delaware on September 17-19, 2007.

Improving peptide-MHC class I binding prediction for unbalanced datasets.

BACKGROUND: Establishment of peptide binding to Major Histocompatibility Complex class I (MHCI) is a crucial step in the development of subunit vaccines and prediction of such binding could greatly reduce costs and accelerate the experimental process of identifying immunogenic peptides. Many methods have been applied to the prediction of peptide-MHCI binding, with some achieving outstanding performance. Because of the experimental methods used to measure binding or affinity between peptides and MHCI molecules, however, available datasets are enriched for nonbinders, and thus highly unbalanced. Although there is no consensus on the ideal class distribution for training sets, extremely unbalanced datasets can be detrimental to the performance of prediction algorithms. RESULTS: We have developed a decision-theoretic framework to construct cost-sensitive trees to predict peptide-MHCI binding and have used them to 1) Assess the impact of the training data's class distribution on classifier accuracy, and 2) Compare resampling and cost-sensitive methods as approaches to compensate for training data imbalance. Our results confirm that highly unbalanced training sets can reduce the accuracy of classifier predictions and show that, in the peptide-MHCI binding context, resampling methods do not improve the classifier performance. In contrast, cost-sensitive methods significantly improve accuracy of decision trees. Finally, we propose the use of a training scheme that, when the training set is enriched for nonbinders, consistently improves the overall classifier accuracy compared to cost-insensitive classifiers and, in particular, increases the sensitivity of the classifiers. This method minimizes the expected classification cost for large datasets. CONCLUSION: Our method consistently improves the performance of decision trees in predicting peptide-MHC class I binding by using cost-balancing techniques to compensate for the imbalance in the training dataset.

Development of a low-cost, insect larvae-derived recombinant subunit vaccine against RHDV.

Vaccine antigens against rabbit hemorrhagic disease virus (RHDV) are currently derived from inactivated RHDV obtained from livers of experimentally infected rabbits. Several RHDV-derived recombinant immunogens have been reported. However, their application in vaccines has been restricted due to their high production costs. In this paper, we describe the development of an inexpensive, safe, stable vaccine antigen for RHDV. A baculovirus expressing a recombinant RHDV capsid protein (VP60r) was used to infect Trichoplusia ni insect larvae. It reached an expression efficiency of 12.5% of total soluble protein, i.e. approximately 2 mg of VP60r per larva. Preservation of the antigenicity and immunogenicity of the VP60r was confirmed by immunological and immunization experiments. Lyophilized crude larvae extracts, containing VP60r, were stable, at room temperature, for at least 800 days. In all cases, rabbits immunized with a single dose of VP60r by the intramuscular route were protected against RHDV challenge. Doses used were as low as 2 microg of VP60r in the presence of adjuvant or 100 microg without one. Orally administered VP60r in the absence of an adjuvant gave no protection. The potential costs of an RHDV vaccine made using this technology would be reduced considerably compared with producing the same protein in insect cells maintained by fermentation. In conclusion, the larva expression system may provide a broad-based strategy for production of recombinant subunit antigens (insectigens) for human or animal medicines, especially when production costs restrain their use.

Improvement of the synthetic tri-peptide vaccine (S3Pvac) against porcine Taenia solium cysticercosis in search of a more effective, inexpensive and manageable vaccine.

Vaccination of pigs may curtail Taenia solium transmission by reducing the number of cysticerci, the precursors of adult intestinal tapeworms in humans. Several antigen preparations induce protection against porcine cysticercosis in experimental settings but only one subunit vaccine (S3Pvac) has been tested and proved effective in the field against naturally acquired disease. Besides improving of the vaccine's effectiveness, significant reductions in production costs and in the logistics of its administration are necessary for the feasibility of nationwide control programs. This review highlights the development of several versions of S3Pvac aimed to increase effectiveness, reduce costs and increase feasibility by novel delivery systems and alternative routes of administration.