Cost-effectiveness Of Vaccination Research Articles

Cost-effectiveness of the adjuvanted quadrivalent influenza vaccine for older adults in South Korea

ABSTRACT South Korea’s National Immunization Program administers the quadrivalent influenza vaccine (QIV) to manage seasonal influenza, with a particular focus on the elderly. After reviewing the safety and immune response triggered by the adjuvanted QIV (aQIV) in individuals aged 65 and older, the Ministry of Food and Drug Safety in Korea approved its use. However, the extensive impact of aQIV on public health is yet to be fully understood. This study assessed the cost-effectiveness of replacing QIV with aQIV in South Korean adults aged 65 years and older. A dynamic transmission model, calibrated with national influenza data, was applied to compare the influence of aQIV and QIV on older adults and the broader population throughout a single influenza season. This study considered both the direct and indirect effects of vaccination on the elderly. We derived the incremental cost-effectiveness ratios (ICERs) from quality-adjusted life-years (QALYs) and costs incurred, validated through a probabilistic sensitivity analysis with 5,000 simulations. Findings suggest that transitioning to aQIV from QIV in the elderly would be cost-effective, particularly if aQIV’s efficacy reaches or exceeds 56.1%. With an ICER of $29,267/QALY, considerably lower than the $34,998/QALY willingness-to-pay threshold, aQIV presents as a cost-effective option. Thus, implementing aQIV with at least 56.1% efficacy is beneficial from both financial and public health perspectives in mitigating seasonal influenza in South Korea.

Cost-Effectiveness of 20-Valent Pneumococcal Conjugate Vaccine in Argentinean Adults.

In Argentina, vaccination with 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23; PCV13 → PPSV23) has been recommended for all adults aged ≥ 65 years and younger adults with chronic medical ("moderate-risk") or immunocompromising ("high-risk") conditions since 2017. With the approval of a 20-valent PCV (PCV20), we evaluated the cost-effectiveness of PCV20 versus current recommendations for moderate-/high-risk adults aged 18-64 years and all adults 65-99 years. A probabilistic cohort model was used to project lifetime outcomes and costs associated with invasive pneumococcal disease (IPD) and all-cause non-bacteremic pneumonia (NBP), and the expected impact of vaccination. Clinical outcomes were projected annually based on Argentinean data. Economic costs were estimated based on cases and corresponding medical costs (adjusted to 2023 USD) and costs of vaccine and administration. Cost-effectiveness of PCV20 was evaluated versus the current strategy, PCV13 → PPSV23, and alternatively, versus sequentially administered 15-valent PCV and PPSV23 (PCV15 → PPSV23), and presented as cost per quality-adjusted life year gained; a healthcare system perspective was used. Costs and benefits were discounted at 3%/year. PCV20 in lieu of PCV13 → PPSV23 among moderate-/high-risk adults aged 18-64 years and all adults 65-99 years (N = 13.4M) prevented 3838 IPD, 4377 inpatient NBP, and 6003 outpatient NBP cases, and 1865 disease-related deaths; relative to PCV15 → PPSV23 the corresponding reductions were 2775, 3285, 4518, and 1348. PCV20 was projected to be the dominant strategy versus PCV13 → PPSV23 and PCV15 → PPSV23 as overall costs were lower by $87.6M and $80.8M, respectively. In probabilistic sensitivity analyses, PCV20 was dominant (i.e., more effective, less costly) in 100% of 1000 simulations. Analyses suggest implementing a PCV20 vaccination program in moderate-/high-risk adults aged 18-64 years and all adults ≥ 65 years-in lieu of PCV13 → PPSV23-would yield substantial reductions in pneumococcal disease and would be cost saving to the Argentinean healthcare system.

Impact of including productivity costs in economic analyses of vaccines for C. difficile infections and infant respiratory syncytial virus, in a UK setting

ObjectivesIt has been estimated that vaccines can accrue a relatively large part of their value from patient and carer productivity. Yet, productivity value is not commonly or consistently considered in health economic evaluations of vaccines in several high-income countries. To contribute to a better understanding of the potential impact of including productivity value on the expected cost-effectiveness of vaccination, we illustrate the extent to which the incremental costs would change with and without productivity value incorporated.MethodsFor two vaccines currently under development, one against Cloistridioides difficile (C. difficile) infection and one against respiratory syncytial disease (RSV), we estimated their incremental costs with and without productivity value included and compared the results.ResultsIn this analysis, reflecting a UK context, a C. difficile vaccination programme would prevent £12.3 in productivity costs for every person vaccinated. An RSV vaccination programme would prevent £49 in productivity costs for every vaccinated person.ConclusionsConsidering productivity costs in future cost-effectiveness analyses of vaccines for C. difficile and RSV will contribute to better-informed reimbursement decisions from a societal perspective.

Efficacy, Effectiveness, and Safety of COVID-19 Vaccine Compared to Placebo in Preventing COVID-19 Infection among 12-17 Years Old: A Systematic Review

Objectives. The World Health Organization recently revised their recommendations and considered healthy children and adolescents as low priority group for COVID-19 vaccine. This review comprehensively assessed existing clinical evidence on COVID-19 vaccine in 12-17 years old. Methods. Included in this review were any type of study that investigated the efficacy, immunogenicity, safety, and effectiveness of COVID-19 vaccine on protection against SARS-COV-2 infection in 12-17 years old. Various electronic databases were searched up to March 15, 2023. Studies were screened, data extracted, risk of bias appraised, and certainty of evidence was judged using GRADE. Review Manager 5.4 was used to estimate pooled effects. Difference between the two groups was described as mean difference for continuous variables and as relative risk or odds ratio for categorical variables. Results. There were six randomized controlled trials and 16 effectiveness studies (8 cohorts and 8 case control). Low certainty evidence showed that BNT162b2 (Pfizer) was effective, immunogenic, and safe in healthy adolescents. There were 15 effectiveness studies on BNT162b2 (Pfizer) in healthy adolescent and one on immunocompromised patients. It was protective against infection with any of the variants, with higher protection against Delta than Omicron. BNT162b2 is protective against hospitalization and emergency and urgent care (high certainty); and critical care and MIS-C (low). Very low certainty evidence noted that BNT 162b2 was also immunogenic in 12-21 years old with rheumatic diseases while on immunomodulatory treatment but with possible increased exacerbation of illness. Low certainty evidence demonstrated that mRNA-1273 (Moderna) was effective, immunogenic, and safe. Low to very low certainty evidence were noted on the safety and immunogenicity of two vector base vaccines (ChAdOx1-19 and Ad5 vector COVID vaccine) and two inactivated vaccines (CoronaVac and BBIBP CorV). Conclusion. There is presently low certainty evidence on the use of RNA vaccines in 12-17 years old. Therecommendation on its use is weak. There is presently insufficient evidence for the use of inactivated andvector-based COVID-19 vaccines. Different countries should consider whether to vaccinate healthy adolescentwithout comprising the other recommended immunization and health priorities that are crucial for this agegroup. Other factors including cost-effectiveness of vaccination and disease burden should be accounted.

Using a Dynamic Model to Estimate the Cost-Effectiveness of HPV Vaccination in Iran.

This study aimed to determine the cost-effectiveness of vaccination against HPV. An age-sex structured dynamic disease transmission model was created to estimate the spread of HPV and the HPV-related incidence of cervical cancer (CC) in Iran. Sixteen age groups of men and women were incorporated to reflect the differences in sexual preferences, vaccination uptake, and disease-related outcomes. Three scenarios were evaluated by using an Incremental Cost-Effectiveness Ratio (ICER) with gained quality-adjusted life years (QALYs). ICER values below one gross domestic product (GDP) per capita are evaluated as highly cost-effective. Vaccination reduces the number of infections and CC-related mortality. Over time, the vaccinated group ages and older age groups experience protection. An initial investment is required and savings in treatment spending reduce the impact over time. Vaccinating girls only was found to be cost-effective, with an ICER close to once the GDP per capita. Vaccinating both sexes was shown to be less cost-effective compared to girls only, and vaccinating boys only was not found to be cost-effective, with an ICER between once and three times, and greater than three times the GDP per capita, respectively. The estimates are conservative since societal cost-saving and the impact of other HPV-related illnesses were not considered and would likely reduce the ICERs.

Cost-effectiveness of 4CMenB vaccination against gonorrhea: importance of dosing schedule, vaccine sentiment, targeting strategy, and duration of protection.

Observational evidence suggests the 4CMenB meningococcal vaccine may partially protect against gonorrhea, with one dose being two-thirds as protective as two. We examined the cost-effectiveness of vaccinating men-who-have-sex-with-men (MSM) in England, with one- or two-dose primary vaccination. Integrated transmission-dynamic health-economic modeling explored the effects of targeting strategy, first- and second-dose uptake levels, and duration of vaccine protection, using observational estimates of vaccine protection. Vaccination with one or two primary doses is always cost-saving, irrespective of uptake, although vaccine sentiment is an important determinant of impact and cost-effectiveness. The most impactful and cost-effective targeting is offering "Vaccination-according-to-Risk" (VaR), to all patients with gonorrhea plus those reporting high numbers of sexual partners. If VaR is not feasible to implement then the more-restrictive strategy of "Vaccination-on-Diagnosis" (VoD) with gonorrhea is cost-effective, but much less impactful. Under conservative assumptions, VaR(2-dose) saves £7.62M(95%CrI:1.15-17.52) and gains 81.41(28.67-164.23) QALYs over 10 years; VoD(2-dose) saves £3.40M(0.48-7.71) and gains 41.26(17.52-78.25) QALYs versus no vaccination. Optimistic versus pessimistic vaccine-sentiment assumptions increase net benefits by ∼30%(VoD) or ∼60%(VaR). At UK costs, targeted 4CMenB vaccination of MSM gains QALYs and is cost-saving at any uptake level. Promoting uptake maximizes benefits and is an important role for behavioral science.

Updated Public Health Impact and Cost Effectiveness of Recombinant Zoster Vaccine in Canadian Adults Aged 50 Years and Older.

The aim of this study was to update previously estimated public health impact and cost effectiveness of recombinant zoster vaccine (RZV) for the prevention of herpes zoster (HZ) in Canadians aged ≥50 years using longer-term RZV efficacy and waning data and real-world coverage and completion. A multicohort Markov model was used to conduct a cost-utility analysis comparing RZV with no HZ vaccination among Canadians aged ≥50 years. Real-world data were used for first-dose coverage (17.5%) and second-dose completion (65%). Vaccine efficacy and waning data were applied from up to 8-year follow-up from the ZOE-50 and ZOE-70 clinical trials. Incremental costs and benefits were calculated using a lifetime horizon from the healthcare payer (base case) and societal perspectives. A discount rate of 1.5% was applied to costs and quality-adjusted life-years (QALYs). The model estimated that RZV would prevent 303,835 HZ cases, 83,256 post-herpetic neuralgia (PHN) cases, 39,653 other complications, and 99 HZ-related deaths compared with no HZ vaccination. Incremental cost-effectiveness ratios (ICERs) were estimated to be $27,486 and $22,097 per QALY (2022 Canadian dollars [CAN$]) from the healthcare payer and societal perspectives, respectively. The base-case ICER was most sensitive to a lower percentage of initial HZ cases with PHN. Almost all probabilistic sensitivity analysis simulations (98.1%) resulted in ICERs <CAN$50,000 per QALY. RZV is expected to remain a cost-effective option for Canadian adults aged ≥50 years when using longer-term RZV efficacy and waning estimates, although the estimated public health impact was smaller than in the previous analysis (due to lower coverage/completion estimates).

Systematic testing in cholera surveillance enhances vaccine impact and cost-effectiveness.

Systematic testing in cholera surveillance enhances vaccine impact and cost-effectiveness.

Cost-effectiveness of an in-development adult-formulated 21-valent pneumococcal conjugate vaccine in US adults aged 50 years or older

Indirect effects of childhood pneumococcal conjugate vaccines (PCV) have diminished the cost-effectiveness of current adult vaccine recommendations. An in-development adult-formulated 21-valent pneumococcal conjugate vaccine (PCV21) may play a critical role in reducing pneumococcal illness by targeting a larger number of serotypes responsible for adult pneumococcal infections. This study assesses the cost-effectiveness of PCV21 in US adults aged 50 years or older compared with currently recommended pneumococcal vaccines, from both the societal and healthcare perspectives. A Markov model evaluated the lifetime cost-effectiveness of PCV21 (given at age 50 years only, at ages 50/65 years, and risk-based at ages < 65 years plus age-based at age 65 years) compared to no vaccination and to currently recommended pneumococcal vaccines given either as currently recommended or routinely at ages 50/65 years. The analysis was conducted in hypothetical Black and non-Black cohorts aged 50 years or older, with and without considering childhood pneumococcal vaccination indirect effects. Model parameters were based on US data. Parameter uncertainty was assessed using 1-way and probabilistic sensitivity analyses.From the societal perspective, PCV21 at ages 50/65 years compared to PCV21 at age 50 years cost $7,410 per quality adjusted life year (QALY) gained in Black cohort analyses and $85,696/QALY gained in the non-Black cohort; PCV21 at ages 50/65 years had the most favorable public health outcomes. From the healthcare perspective, compared to no vaccination, PCV21 at age 50 years cost $46,213/QALY gained in the Black cohort and $86,629/QALY in non-Blacks. All other strategies were dominated in both cohorts and from both perspectives. When considering childhood pneumococcal vaccination indirect effects, costs of PCV21 at ages 50/65 years remained less than $140,000/QALY gained from the societal perspective in both populations. PCV21 is potentially cost-effective compared to currently approved pneumococcal vaccines in adults aged 50 years or older from both the societal and healthcare perspectives.

Cost-Effectiveness of 20-Valent Pneumococcal Conjugate Vaccine Among US Children with Underlying Medical Conditions.

A 20-valent pneumococcal conjugate vaccine (PCV20) was recently recommended for use among US children. We evaluated the cost-effectiveness of PCV20 among children aged 6years with chronic medical conditions (CMC+) and children aged 6years with immunocompromising conditions (IC) versus one and two doses of 23-valent pneumococcal polysaccharide vaccine (PPSV23), respectively. A probabilistic model was employed to depict 10-year risk of clinical outcomes and economic costs of pneumococcal disease, reduction in life years from premature death, and expected impact of vaccination among one cohort of children with CMC+ and IC aged 6years. Vaccine uptake was assumed to be 20% for both PCV20 and PPSV23. Cost per quality-adjusted life year (QALY) gained was evaluated from the US societal and healthcare system perspectives; deterministic and probabilistic sensitivity analyses (DSA/PSA) were also conducted. Among the 226,817 children with CMC+ aged 6 years in the US, use of PCV20 (in lieu of PPSV23) was projected to reduce the number cases of pneumococcal disease by 5203 cases, medical costs by US$8.7 million, and nonmedical costs by US$6.2 million. PCV20 was the dominant strategy versus PPSV23 from both the healthcare and societal perspectives. In the PSA, 99.9% of the 1000 simulations yielded a finding of dominance for PCV20. Findings in analyses of children with IC aged 6years in the USA were comparable (i.e., PCV20 was the dominant vaccination strategy). Scenario analyses showed that increasing PCV20 uptake to 100% could potentially prevent > 22,000 additional cases of pneumococcal disease and further reduce medical and nonmedical costs by US$70.0 million among children with CMC+ and IC. Use of PCV20 among young children with CMC+ and IC in the USA would reduce the clinical burden of pneumococcal disease and yield overall cost savings from both the US healthcare system and societal perspectives. Higher PCV20 uptake could further reduce the number of pneumococcal disease cases in this population.

Shielding Africa, Protecting the World: Unleashing the Power of Preventative Use of Ebola Vaccines

Africa CDC recently conducted a comprehensive risk ranking assessment of epidemic-prone diseases across the continent, identifying Ebola as one of the top 19 infectious diseases with the highest scores in disease severity risk and epidemic potential. The Ebolaviruses first described in the Democratic Republic of the Congo (DRC) in 1976 have left a harrowing trail across sub-Saharan Africa, triggering no less than 34 Ebola outbreaks in 11 sub-Saharan Africa countries, a statistic further compounded by the recent outbreak in Uganda in 2022. At present, the World Health Organization (WHO) has approved two Ebola vaccines, including Ervebo and two-component Zabdeno and Mvabea boost vaccines, for use by individuals above the age of 1 year, including pregnant women as per the Strategic Advisory Group of Experts on Immunization (SAGE) recommendations. The use of these vaccines has demonstrated noteworthy efficacy in safeguarding against Ebola in most African communities and frontline health workers in Ebola-endemic countries such as Sierra Leone, Guinea, and Liberia, among others. Unfortunately, the uptake of these vaccines in Ebola-endemic countries remains dishearteningly constrained despite their availability due to, among other things, the unpredictable timing of outbreaks, sub-optimal surveillance, vaccine demand volatility, palpable vaccine hesitancy, and fragile health infrastructure. Addressing these challenges requires a multifaceted approach that includes a synergy of partnerships between governments, communities, development partners, and private sector partners, such as pharmaceuticals. Recognizing that outbreaks originate and seize at the community level, the imperative of confronting hesitancy through sustained proactive community engagement and utilizing promising vaccination strategies such as ring vaccination must be encouraged. Governments must increase investments to strengthen the regulatory environment for timely access to vaccine stockpiles, robust and cost-effective Ebola vaccination programs for at-risk populations, and preventative use for the health workforce. The International Coordinating Group (ICG) on Vaccine Provision also recommends that national and international health authorities initiate vaccine access by submitting a request to the ICG. This opportunity is at no cost for GAVI-eligible countries and on a reimbursement basis for non-eligible countries. In parallel, Africa CDC is also working closely with Member States on the continent to increase availability and access to medical countermeasures, which include therapeutics, vaccines, and diagnostics, making it critical that Africa CDC is included in the ICG. This will promote timely issue profiling and resolution for increased demand for vaccine stockpiles across the continent where they are needed most as the continent moves towards enhanced health security.

Pneumococcal Vaccination Strategies in 50-Year-Olds to Decrease Racial Disparities: A US Societal Perspective Cost-Effectiveness Analysis

ObjectivesThis study assesses the impact of expanding pneumococcal vaccination to all 50-year-olds to decrease racial disparities by estimating from the societal perspective, the cost-effectiveness of 20-valent pneumococcal conjugate vaccine (PCV20) and 15-valent conjugate vaccine followed by 23-valent polysaccharide vaccine (PCV15/PPSV23) for 50-year-olds. MethodsA Markov model compared the cost-effectiveness of PCV20 or PCV15/PPSV23 in all general population 50- and 65-years-olds compared with current US recommendations and with no vaccination in US Black and non-Black cohorts. US data informed model parameters. Pneumococcal disease societal costs were estimated using direct and indirect costs of acute illness and of pneumococcal-related long-term disability and mortality. Hypothetical 50-year-old cohorts were followed over their lifetimes with costs and effectiveness discounted 3% per year. Deterministic and probabilistic sensitivity analyses assessed model uncertainty. ResultsIn Black cohorts, PCV20 for all at ages 50 and 65 was the least costly strategy and had greater effectiveness than no vaccination and current recommendation strategies, whereas PCV15/PPSV23 at 50 and 65 cost more than $1 million per quality-adjusted life year (QALY) gained compared with PCV20 at 50 and 65. In non-Black cohorts, PCV20 at 50 and 65 cost $62 083/QALY and PCV15/PPSV23 at 50 and 65 cost more than $1 million/QALY with current recommendations, again being more costly and less effective. In probabilistic sensitivity analyses, PCV20 at 50 and 65 was favored in 85.7% (Black) and 61.8% (non-Black) of model iterations at a $100 000/QALY gained willingness-to-pay threshold. ConclusionsWhen considering the societal costs of pneumococcal disease, PCV20 at ages 50 and 65 years in the general US population is a potentially economically viable strategy, particularly in Black cohorts.

Cost-Effectiveness of Human Papillomavirus Vaccination in the UK: Two Versus Single-Dose of Nonavalent HPV Vaccination

IntroductionThe UK implemented a single-dose HPV vaccination policy in September 2023, aiming for sustained protection, better vaccine coverage, and reduced healthcare costs. This research assesses the cost-effectiveness of both one-dose and two-dose schedules from a healthcare perspective. MethodsUsing an age-structured dynamic model, the study analyzed long-term health and economic outcomes of these two different vaccination approaches. It focused on the effects of vaccinating 12- to 13-year-olds with the 9-valent HPV vaccine in either single-dose or two-dose regimens from 2023 to 2093. The analysis, conducted in 2023–2024, explored different immunity durations (10, 30 years, or lifetime) and efficacy levels for the single-dose strategy. ResultsThe study indicated that in the UK, vaccinating 12- to 13-year-olds with a two-dose regimen is not considered cost-effective compared to the single-dose option, assumed to be 90% as effective for ten years. The incremental cost-effectiveness ratios (ICERs) for two doses ranged from £230,903 to £1,082,916 per quality-adjusted life year (QALY), significantly exceeding the UK's £20,000/QALY willingness-to-pay threshold. Over 70 years, a switch from a two-dose to a single-dose vaccination schedule could potentially lead to savings of over £1,073 million in the healthcare system. Furthermore, the single-dose regimen was cost-effective compared to no vaccination, with an ICER below £2,040/QALY. ConclusionsThe study affirms the cost-effectiveness of the UK's single-dose HPV vaccine, in sync with its September 2023 policy shift. The shift not only provides financial benefits but also simplifies vaccine administration, strategically reducing HPV's epidemiological and economic impacts.

Cost-Effectiveness of Respiratory Syncytial Virus Vaccines for Adults

&#x0D; Three economic evaluations and 1 summary of economic evaluations were identified that assessed the cost-effectiveness of 2 respiratory syncytial virus (RSV) vaccines of interest (RSVPreF3 [Arexvy] and RSVpreF [Abrysvo]) compared with no intervention in older adults residing in high-income countries. No economic evaluations assessing mRNA-1345 were identified. No publications investigating RSV vaccination in adults aged 59 years or younger were identified.&#x0D; &#x0D; In total, 5 economic evaluations for RSV vaccines in adults were identified.&#x0D; Four economic evaluations were conducted in the US and 1 was conducted in Hong Kong. All results were presented in terms of incremental cost-utility ratios (i.e., incremental cost per quality-adjusted life-years gained). Net cost per outcome averted was reported for 1 economic evaluation, and cost per hospitalization averted was reported for 3 economic evaluations.&#x0D; The results of all publications found that RSVPreF3 (Arexvy) and RSVpreF (Abrysvo) were more costly and more effective than no intervention for RSV-associated disease. All publications reported that vaccinating older adults against RSV disease was potentially cost-effective. All publications noted that the cost-effectiveness was dependent on vaccine cost, vaccine efficacy, the waning of vaccine protection, RSV hospitalization incidence, health care unit costs, and respective regional willingness-to-pay thresholds.&#x0D; &#x0D; &#x0D; The generalizability of the identified economic evaluations may be limited because the study settings were notably different from Canada. To estimate the cost-effectiveness of RSV vaccinations in Canada, a de novo economic evaluation conducted from a Canadian setting comparing RSVPreF3 (Arexvy), RSVpreF (Abrysvo), and mRNA-1345 is required.&#x0D;

Development of Virus-like Particle Plant-Based Vaccines against Avian H5 and H9 Influenza A Viruses.

Avian influenza A virus (AIV) is a significant cause of mortality in poultry, causing substantial economic loss, particularly in developing countries, and has zoonotic potential. For example, highly pathogenic avian influenza (HPAI) viruses of the H5 subtype have been circulating in Egypt for around two decades. In the last decade, H5N1 viruses of clade 2.2.1 have been succeeded by the antigenically distinct H5N8 clade 2.3.4.4b viruses. Furthermore, H9N2 viruses co-circulate with the H5N8 viruses in Egyptian poultry. It is widely recognised that effective vaccination against IAV requires a close antigenic match between the vaccine and viruses circulating in the field. Therefore, approaches to develop cost-effective vaccines that can be rapidly adapted to local virus strains are required for developing countries such as Egypt. In this project, the haemagglutinin (HA) proteins of Egyptian H5 and H9 viruses were expressed by transient transfection of plants (Nicotiana benthamiana). The formation of virus-like particles (VLPs) was confirmed by transmission electron microscopy. Mice were immunised with four doses of either H5 or H9 VLPs with adjuvant. Antibody and cellular immune responses were measured against the corresponding recombinant protein using ELISA and enzyme-linked immunosorbent assay (ELISpot), respectively. Chickens were immunised with one dose of H5 VLPs, eliciting HA-specific antibodies measured by ELISA and a pseudotyped virus neutralisation test using a heterologous H5 HA. In conclusion, plant-based VLP vaccines have potential for producing an effective vaccine candidate within a short time at a relatively low cost.

Higher-valency pneumococcal conjugate vaccines in older adults, taking into account indirect effects from childhood vaccination: a cost-effectiveness study for the Netherlands

BackgroundNew 15- and 20-valent pneumococcal vaccines (PCV15, PCV20) are available for both children and adults, while PCV21 for adults is in development. However, their cost-effectiveness for older adults, taking into account indirect protection and serotype replacement from a switch to PCV15 and PCV20 in childhood vaccination, remains unexamined.MethodsWe used a static model for the Netherlands to assess the cost-effectiveness of different strategies with 23-valent pneumococcal polysaccharide vaccine (PPV23), PCV15, PCV20, and PCV21 for a 65-year-old cohort from a societal perspective, over a 15-year time horizon. Childhood vaccination was varied from PCV10 to PCV13, PCV15, and PCV20. Indirect protection was assumed to reduce the incidence of vaccine serotypes in older adults by 80% (except for serotype 3, no effect), completely offset by an increase in non-vaccine serotype incidence due to serotype replacement.ResultsIndirect effects from childhood vaccination reduced the cost-effectiveness of vaccination of older adults, depending on the serotype overlap between the vaccines. With PCV10, PCV13, or PCV15 in children, PCV20 was more effective and less costly for older adults than PPV23 and PCV15. PCV20 costs approximately €10,000 per quality-adjusted life year (QALY) gained compared to no pneumococcal vaccination, which falls below the conventional Dutch €20,000/QALY gained threshold. However, with PCV20 in children, PCV20 was no longer considered cost-effective for older adults, costing €22,550/QALY gained. As indirect effects progressed over time, the cost-effectiveness of PCV20 for older adults further diminished for newly vaccinated cohorts. PPV23 was more cost-effective than PCV20 for cohorts vaccinated 3 years after the switch to PCV20 in children. PCV21 offered the most QALY gains, and its cost-effectiveness was minimally affected by indirect effects due to its coverage of 11 different serotypes compared to PCV20.ConclusionsFor long-term cost-effectiveness in the Netherlands, the pneumococcal vaccine for older adults should either include invasive serotypes not covered by childhood vaccination or become more affordable than its current pricing for individual use.

Immunoinformatics, molecular docking and dynamics simulation approaches unveil a multi epitope-based potent peptide vaccine candidate against avian leukosis virus

Lymphoid leukosis is a poultry neoplastic disease caused by avian leukosis virus (ALV) and is characterized by high morbidity and variable mortality rates in chicks. Currently, no effective treatment and vaccination is the only means to control it. This study exploited the immunoinformatics approaches to construct multi-epitope vaccine against ALV. ABCpred and IEDB servers were used to predict B and T lymphocytes epitopes from the viral proteins, respectively. Antigenicity, allergenicity and toxicity of the epitopes were assessed and used to construct the vaccine with suitable adjuvant and linkers. Secondary and tertiary structures of the vaccine were predicted, refined and validated. Structural errors, solubility, stability, immune simulation, dynamic simulation, docking and in silico cloning were also evaluated.The constructed vaccine was hydrophilic, antigenic and non-allergenic. Ramchandran plot showed most of the residues in the favored and additional allowed regions. ProsA server showed no errors in the vaccine structure. Immune simulation showed significant immunoglobulins and cytokines levels. Stability was enhanced by disulfide engineering and molecular dynamic simulation. Docking of the vaccine with chicken’s TLR7 revealed competent binding energies.The vaccine was cloned in pET-30a(+) vector and efficiently expressed in Escherichia coli. This study provided a potent peptide vaccine that could assist in tailoring a rapid and cost-effective vaccine that helps to combat ALV. However, experimental validation is required to assess the vaccine efficiency.

Stable expression of HIV-1 MPER extended epitope on the surface of the recombinant probiotic bacteria Escherichia Coli Nissle 1917 using CRISPR/Cas9

BackgroundMucosal vaccines have the potential to induce protective immune responses at the sites of infection. Applying CRISPR/Cas9 editing, we aimed to develop a probiotic-based vaccine candidate expressing the HIV-1 envelope membrane-proximal external region (MPER) on the surface of E. coli Nissle 1917.ResultsThe HIV-1 MPER epitope was successfully introduced in the porin OmpF of the E. coli Nissle 1917 (EcN-MPER) and the modification was stable over 30 passages of the recombinant bacteria on the DNA and protein level. Furthermore, the introduced epitope was recognized by a human anti-HIV-1 gp41 (2F5) antibody using both live and heat-killed EcN-MPER, and this antigenicity was also retained over 30 passages. Whole-cell dot blot suggested a stronger binding of anti-HIV-1 gp41 (2F5) to heat-killed EcN-MPER than their live counterpart. An outer membrane vesicle (OMV) – rich extract from EcN-MPER culture supernatant was equally antigenic to anti-HIV-1 gp41 antibody which suggests that the MPER antigen could be harboured in EcN-MPER OMVs. Using quantitative ELISA, we determined the amount of MPER produced by the modified EcN to be 14.3 µg/108 cfu.ConclusionsThe CRISPR/Cas9 technology was an effective method for establishment of recombinant EcN-MPER bacteria that was stable over many passages. The developed EcN-MPER clone was devoid of extraneous plasmids and antibiotic resistance genes which eliminates the risk of plasmid transfer to animal hosts, should this clone be used as a vaccine. Also, the EcN-MPER clone was recognised by anti-HIV-1 gp41 (2F5) both as live and heat-killed bacteria making it suitable for pre-clinical evaluation. Expression of OmpF on bacterial surfaces and released OMVs identifies it as a compelling candidate for recombinant epitope modification, enabling surface epitope presentation on both bacteria and OMVs. By applying the methods described in this study, we present a potential platform for cost-effective and rational vaccine antigen expression and administration, offering promising prospects for further research in the field of vaccine development.

The economic burden of Ebola virus disease: a review and recommendations for analysis

Background Ebola virus disease (EVD) continues to be a major public health threat globally, particularly in the low-and-middle-income countries (LMICs) of Africa. The social and economic burdens of EVD are substantial and have triggered extensive research into prevention and control. We aim to highlight the impact and economic implications, identify research gaps, and offer recommendations for future economic studies pertaining to EVD. Method We conducted a comprehensive librarian-led search in PubMed/Medline, Embase, Google Scholar, EconLit and Scopus for economic evaluations of EVD. After study selection and data extraction, findings on the impact and economics of EVD were synthesized using a narrative approach, while identifying gaps, and recommending critical areas for future EVD economic studies. Results The economic evaluations focused on the burden of illness, vaccine cost-effectiveness, willingness-to-pay for a vaccine, EVD funding, and preparedness costs. The estimated economic impact of the 2014 EVD outbreak in Guinea, Liberia, and Sierra Leone across studies ranged from $30 billion to $50 billion. Facility construction and modification emerged as significant cost drivers for preparedness. The EVD vaccine demonstrated cost-effectiveness in a dynamic transmission model; resulting in an incremental cost-effectiveness ratio of about $96 per additional disability adjusted life year averted. Individuals exhibited greater willingness to be vaccinated if it incurred no personal cost, with a minority willing to pay about $1 for the vaccine. Conclusions The severe impact of EVD puts pressure on governments and the international community for better resource utilization and re-allocation. Several technical and methodological issues related to economic evaluation of EVD remain to be addressed, especially for LMICs. We recommend conducting cost-of-sequelae and cost-of-distribution analyses in addition to adapting existing economic analytical methods to EVD. Characteristics of the affected regions should be considered to provide evidence-based economic plans and economic-evaluation of mitigations that enhance resource allocation for prevention and treatment.

Acceptability, cost-effectiveness, and capacity of a facility-based seasonal influenza vaccination among high-risk groups: a study protocol in selected tertiary care hospitals of Bangladesh

BackgroundIn Bangladesh, seasonal influenza imposes considerable disease and economic burden, especially for those at high-risk of severe disease. The most successful approach for influenza prevention is the administration of a vaccine. Many poor and middle-income nations, including Bangladesh, do not have a national strategy or program in place for seasonal influenza vaccines, despite the World Health Organization’s (WHO) advice to prioritize high-risk populations. Additionally, there is a scarcity of substantial data on the cost-effectiveness of seasonal influenza vaccination in these countries. The aim of our study is to determine acceptability, health beliefs, barriers, and intention of receiving influenza vaccine among high-risk populations, assess the cost-effectiveness of implementing a facility-based seasonal influenza vaccination programme, and investigate the required capacity for a potential seasonal influenza vaccination programme.MethodsWe will undertake this study following STROBE guidelines. We will conduct the study in inpatient and outpatient departments of three selected tertiary-level hospitals leveraging the ongoing hospital-based influenza surveillance (HBIS) platform. The study population will include the WHO-defined four high-risk groups excluding healthcare workers: children six months to eight years, pregnant women, elderly ≥ 60 years, and adults with chronic diseases. We will collect quantitative data on participants’ acceptability, health beliefs, barriers, and vaccination intentions using the health belief model (HBM) from patients meeting the criteria for high-risk populations attending two public tertiary-level hospitals. In one of the two public tertiary-level hospitals, we will arrange an influenza vaccination campaign before the influenza season, where the vaccine will be offered free of cost to high-risk patients, and in the second hospital, vaccination will not be offered. Both the vaccinated and unvaccinated participants will then be followed-up once a month for one year to record any influenza-like illness, hospitalization, and death. Additional data for objective two will be collected from patients with symptoms of influenza-like illness (ILI) and severe acute respiratory infection (SARI) at one public and one private hospital to determine both direct and indirect costs associated with influenza illness. We will estimate the required number of influenza vaccines, safe injections, and total storage volume utilizing secondary data. We will use a deterministic Markov decision-analytic model to estimate the cost-effectiveness of facility-based influenza vaccination in Bangladesh.DiscussionThe results of this study will enable the National Immunization Technical Advisory Group and the Ministry of Health & Family Welfare of Bangladesh to decide what steps to take to develop and implement an influenza vaccination strategy targeting high-risk populations.Trial registrationThe Clinicaltrials.gov registration number is NCT05996549. The registration for the protocol version 2.0 took place in August 2023, with the initial participant being enrolled in March 2022.