Browsing by Subject "Vaccination"

Background: To control and minimize the spread of COVID-19, vaccination among the population to achieve herd immunity is important. However, optimizing the vaccination capacity for facility-based vaccination sites and mass vaccination sites is challenging. Additionally, evaluating the impacts of different patient flow arrangements for mass vaccination sites is hard in practice. A study to answer those questions is needed to improve the operation of COVID-19 vaccination sites and reduce the waiting time for patients and cost. Methods: Initially, the time-motion method was used to evaluate the real-world health facilities’ COVID-19 vaccination capacity in China. Then, optimization models were built to determine the optimal capacity levels for different vaccination sites based on the time-motion data. Furthermore, the impacts of different patient flow arrangements were investigated in mass vaccination sites through a discrete event simulation approach. Results: The optimization models established in this study provide tools for policymakers to optimize the capacity level of walk-in COVID-19 vaccination sites for different vaccination targets while considering the cross-infectious risk. Compared to facility-based vaccination sites, a single mass vaccination site will require fewer service desks than using multiple facility-based vaccination sites. The mass vaccination site arranged with an optimal capacity level using a pooled queue tends to be more flexible compared to real-world arrangements. Conclusions: This research developed a modeling framework that can help to optimize the service capacity level, identify the trade-off points for vaccination planning, and reduce the cost of operating the vaccination sites to aid in the planning of the COVID-19 vaccination site.

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Influenza causes an estimated 3 to 5 million cases of severe illness annually, along with substantial morbidity and mortality, particularly among low and middle-income countries (LMICs). The most effective way to decrease the burden of influenza is vaccination. Currently, Sri Lanka has no influenza vaccination policies and does not offer vaccination within the public healthcare sector. Therefore, a cost-effectiveness analysis of influenza vaccine implementation for the Sri Lankan population was performed. A static Markov model that did not account for transmission dynamics was used for this study. The model followed a theoretical cohort of Sri Lankans from all ages through two potential scenarios: universal influenza vaccination and no influenza vaccination across twelve-monthly cycles. Cost-effectiveness was analyzed using a governmental perspective at the national level. Costs for the study were broken down into three categories: direct, indirect, and vaccine costs. All costs were identified from previous literature for the local context. Vaccine efficacy was expressed as a range (48% to 72%) identified from a previous meta-analysis investigating similar settings. One model arm was considered cost-effective if the ICER was below a three-fold gross domestic product (GDP) per capita per DALY averted limit and highly cost-effective if below a one-fold GDP per capita per DALY averted limit. Utilizing TreeAge Pro software, we conducted both probabilistic sensitivity analyses and one-way sensitivity analyses for all model variables. The vaccination model arm reduced all influenza outcomes by approximately 60% (170,283 episodes, 3,167 hospitalizations, and 152 deaths) compared to no vaccination. By implementing vaccination earlier in the year, this reduction in the influenza disease burden was maximized. Vaccination was considered cost-effective compared to no vaccination, with a base case incremental cost-effectiveness ratio (ICER) estimated at Rs. 968,071.45 /DALY (5,418.62 USD/DALY). Sensitivity analysis identified that the ICER was sensitive to implementation month, monthly probability of contracting influenza, cost of vaccination, and years of life disabled. Due to only considering a one-year period, the implementation month had the most substantial effect on the ICER because no potential rollover effects of vaccination could be seen for the later implementation months. Probabilistic sensitivity analyses were performed on all variables, and there was a 99% probability that vaccination was cost-effective below a WTP threshold of 1,157,047.92 Rs/DALY (6,476.38 USD/DALY). No value for a variable within our estimated ranges resulted in ICERs above the WTP threshold of Rs. 2,066,157 (USD 11,556) per DALY averted. In conclusion, vaccination was considered cost-effective when compared to the implementation of no vaccine. However, due to a lack of national data, large-scale national studies are needed to determine better the influenza disease burden, at-risk population, and implementation cost.

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The receptor-recognized form of α₂-macroglobulin (α₂M*) targets antigens (Ag) to professional Ag-presenting cells (APCs) for rapid internalization, processing, and presentation. When employed as an Ag delivery vehicle, α₂M* amplifies major histocompatibility complex (MHC) class II presentation as demonstrated by increased antibody (Ab) titers. Recent evidence, however, suggests that α₂M*-encapsulation may also enhance Ag-specific cytotoxic T lymphocyte (CTL) immunity. In these studies, we demonstrate that α₂M*-delivered Ag (ovalbumin, OVA) enhances the production of specific in vitro and in vivo CTL responses.

Murine splenocytes expressing a transgenic T cell receptor (TCR) specific for CTL peptide OVA_257-264 (SIINFEKL) demonstrated up to 25-fold greater IFN-γ and IL-2 secretion when treated in vitro with α₂M*-OVA compared to soluble OVA. The frequency of IFN-γ -producing cells was increased ~15-fold as measured by ELISPOT. Expansion of the OVA-specific CD8+ T cells, as assayed by tetramer binding and [3H]thymidine incorporation, and cell-mediated cytotoxicity, as determined by a flow cytometric assay, were also significantly enhanced by α₂M*-OVA. Furthermore, CTL responses were observed at Ag doses tenfold lower than those required with OVA alone.

We also observed enhanced humoral and CTL responses by naïve mice following intradermal immunization with α₂M*-OVA. These α₂M*-OVA-immunized mice displayed increased protection against a subcutaneously implanted OVA-expressing tumor, as demonstrated by delayed tumor growth and prolonged animal survival. The anti-tumor response observed with α₂M*-mediated Ag delivery was comparable to that of an accepted vaccine adjuvant (CpG 1826) and appeared superior to a cell-based vaccine technique.

To further understand the mechanism underlying this enhanced CTL immunity, the subsets of professional APCs capable of cross-presenting α₂M*-encapsulated Ag were investigated. Although both dendritic cells (DCs) and macrophages appear to stimulate some degree of cross-priming in response to α₂M*-encapsulated Ag, CD8+CD4- and CD8-CD4+ DCs appear to do so with the greatest efficiency. The implications of this finding to the ongoing debate regarding the relative contributions of APC subsets to Ag cross-presentation and the determinants of which cells cross-present with high efficiency are discussed.

These observations demonstrate that α₂M*-mediated Ag delivery promotes cross-presentation resulting in enhanced Ag-specific CTL immunity. Considered in the context of previous work, these results support α₂M* as an effective Ag delivery system that may be particularly useful for vaccines based on weakly immunogenic subunits or requiring dose sparing.