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BACKGROUND: With coronavirus disease 2019 (COVID-19) vaccination no longer mandated by many businesses/organizations, it is now up to individuals to decide whether to get any new boosters/updated vaccines going forward. METHODS: We developed a Markov model representing the potential clinical/economic outcomes from an individual perspective in the United States of getting versus not getting an annual COVID-19 vaccine. RESULTS: For an 18-49 year old, getting vaccinated at its current price ($60) can save the individual on average $30-$603 if the individual is uninsured and $4-$437 if the individual has private insurance, as long as the starting vaccine efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is ≥50% and the weekly risk of getting infected is ≥0.2%, corresponding to an individual interacting with 9 other people in a day under Winter 2023-2024 Omicron SARS-CoV-2 variant conditions with an average infection prevalence of 10%. For a 50-64 year old, these cost-savings increase to $111-$1278 and $119-$1706 for someone without and with insurance, respectively. The risk threshold increases to ≥0.4% (interacting with 19 people/day), when the individual has 13.4% preexisting protection against infection (eg, vaccinated 9 months earlier). CONCLUSIONS: There is both clinical and economic incentive for the individual to continue to get vaccinated against COVID-19 each year.
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Vacunas contra la COVID-19 , COVID-19 , Análisis Costo-Beneficio , Cadenas de Markov , SARS-CoV-2 , Vacunación , Humanos , COVID-19/prevención & control , COVID-19/economía , COVID-19/epidemiología , Vacunas contra la COVID-19/economía , Vacunas contra la COVID-19/administración & dosificación , Persona de Mediana Edad , Adulto , Adolescente , SARS-CoV-2/inmunología , Vacunación/economía , Adulto Joven , Estados Unidos/epidemiología , Masculino , FemeninoRESUMEN
Here we describe the in vitro preparation of mRNA from DNA templates, including setting up the transcription reaction, mRNA capping, and mRNA labeling. We then describe methods used for mRNA characterization, including UV and fluorescence spectrophotometry, as well as gel electrophoresis. Moreover, characterization of the in vitro transcribed RNA using the Bioanalyzer instrument is described, allowing a higher resolution analysis of the target molecules. For the in vitro testing of the mRNA molecules, we include protocols for the transfection of various primary cell cultures and the confirmation of translation by intracellular staining and western blotting.
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ARN Mensajero , Transcripción Genética , ARN Mensajero/genética , Humanos , Transfección/métodos , Caperuzas de ARN/genética , Caperuzas de ARN/metabolismo , ADN/genética , AnimalesRESUMEN
Lyme disease, caused by Lyme Borrelia spirochetes, is the most common vector-borne illness in the United States. Despite its global significance, with an estimated 14.5 % seroprevalence, there is currently no licensed vaccine. Previously, we demonstrated that CspZ-YA protein conferred protection against Lyme Borrelia infection, making it a promising vaccine candidate. However, such a protein was tagged with hexahistidine, and thus not preferred for vaccine development; furthermore, the formulation to stabilize the protein was understudied. In this work, we developed a two-step purification process for tag-free E. coli-expressed recombinant CspZ-YA. We further utilized various bioassays to analyze the protein and determine the suitable buffer system for long-term storage and formulation as a vaccine immunogen. The results indicated that a buffer with a pH between 6.5 and 8.5 stabilized CspZ-YA by reducing its surface hydrophobicity and colloidal interactions. Additionally, low pH values induced a change in local spatial conformation and resulted in a decrease in α-helix content. Lastly, an optimal salinity of 22-400 mM at pH 7.5 was found to be important for its stability. Collectively, this study provides a fundamental biochemical and biophysical understanding and insights into the ideal stabilizing conditions to produce CspZ-YA recombinant protein for use in vaccine formulation and development.
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Borrelia burgdorferi , Enfermedad de Lyme , Humanos , Vacunas contra Enfermedad de Lyme , Escherichia coli/genética , Estudios Seroepidemiológicos , Enfermedad de Lyme/prevención & control , Proteínas de la Membrana Bacteriana Externa/químicaRESUMEN
Background: With efforts underway to develop a universal coronavirus vaccine, otherwise known as a pan-coronavirus vaccine, this is the time to offer potential funders, researchers, and manufacturers guidance on the potential value of such a vaccine and how this value may change with differing vaccine and vaccination characteristics. Methods: Using a computational model representing the United States (U.S.) population, the spread of SARS-CoV-2 and the various clinical and economic outcomes of COVID-19 such as hospitalisations, deaths, quality-adjusted life years (QALYs) lost, productivity losses, direct medical costs, and total societal costs, we explored the impact of a universal vaccine under different circumstances. We developed and populated this model using data reported by the CDC as well as observational studies conducted during the COVID-19 pandemic. Findings: A pan-coronavirus vaccine would be cost saving in the U.S. as a standalone intervention as long as its vaccine efficacy is ≥10% and vaccination coverage is ≥10%. Every 1% increase in efficacy between 10% and 50% could avert an additional 395,000 infections and save $1.0 billion in total societal costs ($45.3 million in productivity losses, $1.1 billion in direct medical costs). It would remain cost saving even when a strain-specific coronavirus vaccine would be subsequently available, as long as it takes at least 2-3 months to develop, test, and bring that more specific vaccine to the market. Interpretation: Our results provide support for the development and stockpiling of a pan-coronavirus vaccine and help delineate the vaccine characteristics to aim for in development of such a vaccine. Funding: The National Science Foundation, the Agency for Healthcare Research and Quality, the National Institute of General Medical Sciences, the National Center for Advancing Translational Sciences, and the City University of New York.
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Chagas disease (CD) (American trypanosomiasis caused by Trypanosoma cruzi) is a parasitic disease endemic in 21 countries in South America, with increasing global spread. When administered late in the infection, the current antiparasitic drugs do not prevent the onset of cardiac illness leading to chronic Chagasic cardiomyopathy. Therefore, new therapeutic vaccines or immunotherapies are under development using multiple platforms. In this study, we assessed the feasibility of developing an mRNA-based therapeutic CD vaccine targeting two known T. cruzi vaccine antigens (Tc24âa flagellar antigen and ASP-2âan amastigote antigen). We present the mRNA engineering steps, preparation, and stability of the lipid nanoparticles and evaluation of their uptake by dendritic cells, as well as their biodistribution in c57BL/J mice. Furthermore, we assessed the immunogenicity and efficacy of two mRNA-based candidates as monovalent and bivalent vaccine strategies using an in vivo chronic mouse model of CD. Our results show several therapeutic benefits, including reductions in parasite burdens and cardiac inflammation, with each mRNA antigen, especially with the mRNA encoding Tc24, and Tc24 in combination with ASP-2. Therefore, our findings demonstrate the potential of mRNA-based vaccines as a therapeutic option for CD and highlight the opportunities for developing multivalent vaccines using this approach.
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Enfermedad de Chagas , Vacunas Antiprotozoos , Ratones , Animales , ARN , Distribución Tisular , Enfermedad de Chagas/prevención & control , Antígenos de Protozoos/genética , ARN Mensajero , TecnologíaRESUMEN
INTRODUCTION: Zebrafishes represent a proven model for human diseases and systems biology, exhibiting physiological and genetic similarities and having innate and adaptive immune systems. However, they are underexplored for human vaccinology, vaccine development, and testing. Here we summarize gaps and challenges. AREAS COVERED: Zebrafish models have four potential applications: 1) Vaccine safety: The past successes in using zebrafishes to test xenobiotics could extend to vaccine and adjuvant formulations for general safety or target organs due to the zebrafish embryos' optical transparency. 2) Innate immunity: The zebrafish offers refined ways to examine vaccine effects through signaling via Toll-like or NOD-like receptors in zebrafish myeloid cells. 3) Adaptive immunity: Zebrafishes produce IgM, IgD,and two IgZ immunoglobulins, but these are understudied, due to a lack of immunological reagents for challenge studies. 4) Systems vaccinology: Due to the availability of a well-referenced zebrafish genome, transcriptome, proteome, and epigenome, this model offers potential here. EXPERT OPINION: It remains unproven whether zebrafishes can be employed for testing and developing human vaccines. We are still at the hypothesis-generating stage, although it is possible to begin outlining experiments for this purpose. Through transgenic manipulation, zebrafish models could offer new paths for shaping animal models and systems vaccinology.
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Inmunidad Adaptativa , Adyuvantes Inmunológicos , Inmunidad Innata , Modelos Animales , Desarrollo de Vacunas , Vacunas , Pez Cebra , Pez Cebra/inmunología , Animales , Adyuvantes Inmunológicos/administración & dosificación , Humanos , Vacunas/inmunología , Vacunas/administración & dosificación , Vacunología/métodosRESUMEN
The development of broad-spectrum coronavirus vaccines is essential to prepare for future respiratory virus pandemics. We demonstrated broad neutralization by a trivalent subunit vaccine, formulating the receptor-binding domains of SARS-CoV, MERS-CoV, and SARS-CoV-2 XBB.1.5 with Alum and CpG55.2. Vaccinated mice produced cross-neutralizing antibodies against all three human Betacoronaviruses and others currently exclusive to bats, indicating the epitope preservation of the individual antigens during co-formulation and the potential for epitope broadening.