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1.
Methods Mol Biol ; 2834: 303-332, 2025.
Artículo en Inglés | MEDLINE | ID: mdl-39312172

RESUMEN

In the last three decades, the development of nanoparticles or nano-formulations as drug delivery systems has emerged as a promising tool to overcome the limitations of conventional delivery, potentially to improve the stability and solubility of active molecules, promote their transport across the biological membranes, and prolong circulation times to increase efficacy of a therapy. Despite several nano-formulations having applications in drug delivery, some issues concerning their safety and toxicity are still debated. This chapter describes the recent available information regarding safety, toxicity, and efficacy of nano-formulations for drug delivery. Several key factors can influence the behavior of nanoparticles in a biological environment, and their evaluation is crucial to design non-toxic and effective nano-formulations. Among them, we have focused our attention on materials and methods for their preparation (including the innovative microfluidic technique), mechanisms of interactions with biological systems, purification of nanoparticles, manufacture impurities, and nano-stability. This chapter places emphasis on the utilization of in silico, in vitro, and in vivo models for the assessment and prediction of toxicity associated with these nano-formulations. Furthermore, the chapter includes specific examples of in vitro and in vivo studies conducted on nanoparticles, illustrating their application in this field.


Asunto(s)
Sistemas de Liberación de Medicamentos , Nanopartículas , Humanos , Nanopartículas/química , Animales , Sistemas de Liberación de Medicamentos/métodos , Composición de Medicamentos/métodos , Sistema de Administración de Fármacos con Nanopartículas/química
2.
Arch Acad Emerg Med ; 13(1): e6, 2025.
Artículo en Inglés | MEDLINE | ID: mdl-39318867

RESUMEN

Introduction: In January 2020, WHO declared the 2019 Coronavirus Disease (COVID-19) a pandemic. Though COVID-19 vaccines are recommended, ongoing surveillance is crucial due to potential unforeseen events. Evaluation of long-term effectiveness and safety and addressing emerging variants are vital. This study integrates systematic reviews to assess COVID-19 vaccine efficacy, immunogenicity, and safety comprehensively. Methods: This study was an umbrella review study on the feasibility and effectiveness of vaccines for COVID-19. We conducted a comprehensive search in PubMed, Web of Sciences, and Scopus, using MeSH terms and keywords related to COVID-19 vaccines. Inclusion criteria comprised peer-reviewed systematic reviews and meta-analyses in English, focusing on feasibility and effectiveness. Exclusion criteria targeted non-systematic reviews exclusively on vaccine safety and duplicates. Two independent reviewers screened and resolved discrepancies. Data extraction included key details. Methodological quality was assessed using the ROBIS tool. Data synthesis involves narrative and, if applicable, quantitative synthesis (meta-analysis). Reporting followed PRISMA guidelines. Results: A total of 32 systematic reviews were included in the study, of which 20 also conducted a meta-analysis. The studies investigated in the included reviews ranged from 7 to 74. The included articles were conducted in various countries around the globe. The findings indicated that COVID-19 vaccines are generally safe and effective for individuals with various medical conditions. The overall risk of bias for the included studies was assessed as low risk. Conclusion: The study outcomes indicated that mRNA vaccines exhibit a higher incidence of adverse events but demonstrate greater efficacy. Conversely, inactivated and protein subunit vaccines are safer but exhibit lower efficiency. Moreover, the vaccine is considered safe for individuals with specific conditions such as inflammatory bowel disease, solid organ transplant recipients, children, pregnant individuals, and those with hematologic problems. Ultimately, the acceptance of the COVID-19 vaccine among individuals is influenced by various factors, including geographic, socioeconomic, and pandemic-related considerations.

3.
Rev. enferm. UERJ ; 32: e76740, jan. -dez. 2024.
Artículo en Inglés, Español, Portugués | LILACS-Express | LILACS | ID: biblio-1556396

RESUMEN

Objetivo: analisar o cenário de vacinação contra Covid-19 na população privada de liberdade em um estado do Nordeste brasileiro. Método: estudo do tipo observacional e ecológico, com os dados extraídos do Sistema de informações penitenciário brasileiro e dos boletins publicados pelo Conselho Nacional de Justiça, referentes a outubro de 2021 a junho de 2022, submetidos à análise estatística descritiva, por meio de frequências absolutas e relativas. Resultados: verificou-se que, entre 4.345 pessoas privadas de liberdade com a primeira dose de vacinação contra Covid-19, apenas 573 possuíam a segnda dose e nenhuma a terceira dose. Conclusão: evidenciou-se que, apesar da vacinação ser um benefício, ainda é um grande desafio para ser implementada para a população privada de liberdade, visto que, mesmo sendo considerados grupos prioritários, o acesso a esse direito foi prejudicado para esses indivíduos.


Objective: to analyze the Covid-19 vaccination scenario in the population deprived of liberty in a state in the Brazilian Northeast. Method: observational and ecological study, with data extracted from the Brazilian Penitentiary Information System and the bulletins published by the National Council of Justice, referring to October 2021 to June 2022, submitted to descriptive statistical analysis, using absolute and relative frequencies. Results: it was found that of the 4,345 people deprived of their liberty who had received the first dose of Covid-19 vaccination, only 573 had received the second dose and none had received the third dose. Conclusion: it was evident that, although vaccination is a benefit, it is still a major challenge to implement it for the population deprived of their liberty, since even though they are considered priority groups, access to this right has been hampered for these individuals.


Objetivo: analizar el escenario de vacunación contra el Covid-19 en la población privada de libertad en un estado del Nordeste brasileño. Método: estudio observacional y ecológico, con datos extraídos del Sistema de Información Penitenciaria de Brasil y boletines publicados por el Consejo Nacional de Justicia, correspondientes al periodo entre octubre de 2021 y junio de 2022, sometidos a análisis estadístico descriptivo, utilizando frecuencias absolutas y relativas. Resultados: se encontró que, de las 4.345 personas privadas de libertad con la primera dosis de la vacuna contra el Covid-19, solo 573 contaban con la segunda dosis y ninguna tenía la tercera dosis. Conclusión: se observó que, pese a que la vacunación es un beneficio, sigue siendo un gran desafío implementarla para la población privada de libertad, ya que, si bien se los consideran grupos prioritarios, el acceso a este derecho se vio afectado para estos individuos.

4.
Nature ; 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39232237
5.
Front Immunol ; 15: 1455730, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39234239

RESUMEN

Introduction: Various COVID-19 vaccine trials have shown that vaccines can successfully prevent symptomatic cases of COVID-19 and death. Head-to-head comparisons help to better understand the immune response characteristics of different COVID-19 vaccines in humans. Methods: We randomly selected 20 participants from each of five ongoing Phase II trials of COVID-19 vaccines. Here, SARS-CoV 2-specific immune responses to DNA vaccine (INO-4800), mRNA vaccine (BNT162b2), Adenovirus-vectored vaccine (CONVIDECIA), Protein subunit vaccine (Recombinant COVID- 19 Vaccine (Sf9 Cells)), Inactivated Vaccine (KCONVAC) were examined longitudinally in healthy adults between Jan 15, 2021 and July 5, 2021 for 6 months. RBD-IgG titres were detected by ELISA, neutralising antibody titer were detected by pseudoviral neutralization and immune cell response were detected by flow cytometry. Results: At the first visit (V1), 100% of individuals who received the BNT162b2, CONVIDECIA, or KCONVAC vaccines experienced seroconversion of neutralizing and binding antibodies in the serum. Except for the Recombinant COVID-19 Vaccine (Sf9 Cells) vaccine having the highest neutralizing antibody GMT at the second visit (although there was no statistically significant difference in geometric mean titers between V1 and V2), the rest of the vaccines had the highest levels of binding antibodies and neutralizing antibodies at V1. The neutralizing antibodies GMT of all vaccines showed a significant decrease at V3 compared to V1. The neutralizing antibody GMT against the omicron variant of all vaccines at V1 showed a significant decrease compared to the wild strain. We observed statistically significant differences in Tcm cells and RBD-specific memory B cells among various vaccines. Discussion: BNT162b2 (mRNA vaccine) exhibits the highest antibody levels among the five vaccines evaluated, regardless of whether the target is the wild-type virus or its variants. However, its cellular immune response may be weaker compared to CONVIDECIA (adenovirus type 5 vector vaccine).


Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Inmunidad Celular , Inmunidad Humoral , SARS-CoV-2 , Humanos , Vacunas contra la COVID-19/inmunología , Adulto , COVID-19/inmunología , COVID-19/prevención & control , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , SARS-CoV-2/inmunología , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Masculino , Femenino , China , Persona de Mediana Edad , Adulto Joven , Vacunas de Subunidad/inmunología , Vacunas de ADN/inmunología , Vacuna BNT162/inmunología , Inmunogenicidad Vacunal , Vacunas de Productos Inactivados/inmunología
7.
Int Immunopharmacol ; 142(Pt B): 113157, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39288629

RESUMEN

Nucleic acid is an essential biopolymer in all living cells, performing the functions of storing and transmitting genetic information and synthesizing protein. In recent decades, with the progress of science and biotechnology and the continuous exploration of the functions performed by nucleic acid, more and more studies have confirmed that nucleic acid therapy for living organisms has great medical therapeutic potential. Nucleic acid drugs began to become independent therapeutic agents. As a new therapeutic method, nucleic acid therapy plays an important role in the treatment of genetic diseases, viral infections and cancers. There are currently 19 nucleic acid drugs approved by the Food and Drug Administration (FDA). In the following review, we start from principles and advantages of nucleic acid therapy, and briefly describe development history of nucleic acid drugs. And then we give examples of various RNA therapeutic drugs, including antisense oligonucleotides (ASO), mRNA vaccines, small interfering RNA (siRNA) and microRNA (miRNA), aptamers, and small activating RNA (saRNA). In addition, we also focused on the current status of nucleic acid drugs used in cancer therapy and the breakthrough in recent years. Clinical trials of nucleic acid drugs for cancer treatment are under way, conventional radiotherapy and chemotherapy combined with the immunotherapies such as checkpoint inhibitors and nucleic acid drugs may be the main prospects for successful cancer treatment.

8.
J Med Econ ; 27(1): 1190-1196, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39231068

RESUMEN

OBJECTIVE: To compare healthcare resource utilization (HCRU) and all-cause medical costs among individuals aged ≥50 years who received influenza and COVID-19 vaccines on the same day and those who received influenza vaccine only. METHODS: We conducted a retrospective cohort study leveraging Optum's de-identified Clinformatics DataMart from 8/31/2021 to 7/31/2023. Individuals aged ≥50 years continuously enrolled in health plans for 1 year prior and until 7/31/2023 were included. Two cohorts were formed based on vaccination status between 8/31/2022 and 1/31/2023: co-administered influenza and COVID-19 vaccines (co-admin cohort) and influenza vaccine only (influenza cohort). Associations between vaccination status and all-cause, influenza-related, COVID-related, pneumonia-related, and cardiorespiratory-related hospitalization, outpatient or emergency room visits and all-cause medical costs were estimated by weighted generalized linear models, adjusting for confounding by stabilized inverse probability of treatment weighting. RESULTS: 613,156 (mean age: 71) and 1,340,011 (mean age: 72) individuals were included in the co-admin and influenza cohorts, respectively. After weighting, the baseline characteristics were balanced between cohorts. The co-admin cohort was at statistically significant lower risk of all-cause (RR: 0.95, 95% CI: 0.93-0.96), COVID-19-related (RR: 0.59, 95% CI: 0.56-0.63), cardiorespiratory-related (RR: 0.94, 95% CI: 0.93-0.96) and pneumonia-related (RR: 0.86, 95% CI: 0.83-0.90) hospitalization but not influenza-related hospitalizations (RR: 0.91, 95% CI: 0.81, 1.04) compared with the influenza cohort. Co-administration was associated with 3% lower all-cause medical cost (cost ratio: 0.974, 95% CI: 0.968, 0.979) during the follow-up period compared to receiving influenza vaccine only. LIMITATIONS: Limitations include the potential residual confounding bias in observational data, measurement errors from claims data, and that the cohort was followed for a single season. CONCLUSION: Receiving co-administered COVID-19 and influenza vaccines versus only receiving influenza vaccination reduced the risk of HCRU, especially COVID-19-related hospitalization and all-cause medical costs. Increasing vaccine coverage, particularly for COVID-19, might have public health and economic benefits.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Vacunas contra la Influenza , Gripe Humana , Humanos , Vacunas contra la Influenza/administración & dosificación , Vacunas contra la Influenza/economía , Anciano , Estudios Retrospectivos , Femenino , Masculino , Persona de Mediana Edad , Gripe Humana/prevención & control , Gripe Humana/economía , COVID-19/prevención & control , COVID-19/economía , Vacunas contra la COVID-19/economía , Vacunas contra la COVID-19/administración & dosificación , Hospitalización/economía , Hospitalización/estadística & datos numéricos , Recursos en Salud/economía , Recursos en Salud/estadística & datos numéricos , SARS-CoV-2 , Aceptación de la Atención de Salud/estadística & datos numéricos
9.
Artículo en Inglés | MEDLINE | ID: mdl-39306084

RESUMEN

INTRODUCTION: During the SARS-CoV-2 pandemic, immune-mediated neurological events have been described in patients vaccinated against the virus or who have overcome the disease. Among these events is Idiopathic peripheral facial palsy or Bell's palsy. OBJECTIVES: To study the incidence of Bell's Palsy in the ENT emergency department of a tertiary hospital in Catalonia during the SARS-CoV-2 pandemic. METHODS: Retrospective historical cohort comparison study of patients diagnosed with Bell's palsy between January 2018 and December 2021. Crude incidence rates were calculated as the total number of events divided by person time at risk per 100.000 person-years. Observed (2020, 2021) and historical (2018, 2019) rates were compared using standardized incidence rates with corresponding 95% confidence intervals. RESULTS: Of the total number of ENT emergency department visits from 2018 to 2021 (22.658), there were 247 cases of Bell's palsy. The incidence rate of Bell's palsy in the pre-pandemic group was 12,2 and 10,9 per 100.000 person-years for 2018 and 2019, respectively. The 2020 standardized incidence rate of Bell's palsy was 0,70 [95% CI 0,49-1,01] and 1,25 [95% CI 0,93-1,67] for 2021. No significant differences were evident between the two groups. CONCLUSION: In our cohort, no association was found between vaccination or COVID-19 infection and the development of Bell's Palsy.

10.
Antibodies (Basel) ; 13(3)2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39311377

RESUMEN

In the post-pandemic era, evaluating long-term immunity against COVID-19 has become increasingly critical, particularly in light of continuous SARS-CoV-2 mutations. This study aimed to assess the long-term humoral immune response in sera collected in Makassar. We measured anti-RBD IgG levels and neutralization capacity (NC) against both the Wild-Type (WT) Wuhan-Hu and Omicron XBB.1.5 variants across groups of COVID-19-vaccinated individuals with no booster (NB), single booster (SB), and double booster (DB). The mean durations since the last vaccination were 25.11 months, 19.24 months, and 16.9 months for the NB, SB, and DB group, respectively. Additionally, we evaluated the effect of breakthrough infection (BTI) history, with a mean duration since the last confirmed infection of 21.72 months. Our findings indicate fair long-term WT antibody (Ab) titers, with the DB group showing a significantly higher level than the other groups. Similarly, the DB group demonstrated the highest anti-Omicron XBB.1.5 Ab titer, yet it was insignificantly different from the other groups. Although the level of anti-WT Ab titers was moderate, we observed near-complete (96-97%) long-term neutralization against the WT pseudo-virus for all groups. There was a slight decrease in NC against Omicron XBB.1.5 compared to the WT among all groups, as DB group, SB group, and NB group showed 80.71 ± 3.9%, 74.29 ± 6.7%, and 67.2 ± 6.3% neutralization activity, respectively. A breakdown analysis based on infection and vaccine status showed that booster doses increase the NC against XBB.1.5, particularly in individuals without BTI. Individuals with BTI demonstrate a better NC compared to their counterpart uninfected individuals with the same number of booster doses. Our findings suggest that long-term immunity against SARS-CoV-2 persists and is effective against the mutant variant. Booster doses enhance the NC, especially among uninfected individuals.

11.
Expert Opin Biol Ther ; : 1-9, 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39311611

RESUMEN

INTRODUCTION: Cervical cancer remains one of the most common gynecologic malignancies worldwide. A disproportionate burden of cases occurs in developing countries due to inadequate screening and treatment. Even among patients adequately treated, in the presence of locally advanced or recurrent disease, outcomes tend to be poor. The introduction of biologic therapy into treatment has increased overall survival; however, a considerable opportunity still exists to improve current standards in treatment. Biologics have shown antitumor activity in multiple tumor types and are actively being pursued for the management of cervical cancer. AREAS COVERED: In this article, we will discuss the historical evolution of biologic therapy in cervical cancer including use of angiogenesis inhibitors, immune checkpoint inhibitors, antibody-drug conjugates, and vaccines. We will review how these therapies have been integrated into current treatment recommendations and discuss ongoing investigations intended to improve clinical outcomes. We also postulate on persistent gaps in care. EXPERT OPINION: Biologic therapies have had a tremendous impact on our current approach to managing cervical cancer. We anticipate that significant more research and development will be committed to the continued investigation of biologics in cervical cancer in an effort to improve a historically difficult to treat malignancy.

13.
JCI Insight ; 9(18)2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39315545

RESUMEN

BACKGROUNDThe level of nasal spike-specific secretory IgA (sIgA) is inversely correlated with the risk of SARS-CoV-2 Omicron infection. This study aimed to evaluate the safety and immunogenicity of intranasal vaccination using Ad5-S-Omicron (NB2155), a replication-incompetent human type 5 adenovirus carrying Omicron BA.1 spike.METHODSAn open-label, single-center, investigator-initiated trial was carried out on 128 health care workers who had never been infected with SARS-CoV-2 and had previously received 2 or 3 injections of inactivated whole-virus vaccines, with the last dose given 3-19 months previously (median 387 days, IQR 333-404 days). Participants received 2 intranasal sprays of NB2155 at 28-day intervals between November 30 and December 30, 2022. Safety was evaluated by solicited adverse events and laboratory tests. The elevation of nasal mucosal spike-specific sIgA and serum neutralizing activities were assessed. All participants were monitored for infection by antigen tests, disease symptoms, and the elevation of nucleocapsid-specific sIgA in the nasal passage.RESULTSThe vaccine-related solicited adverse events were mild. Nasal spike-specific sIgA against 10 strains had a mean geometric mean fold increase of 4.5 after the first dose, but it increased much higher to 51.5 after the second dose. Serum neutralizing titers also increased modestly to 128.1 (95% CI 74.4-220.4) against authentic BA.1 and 76.9 (95% CI 45.4-130.2) against BA.5 at 14 days after the second dose. Due to the lifting of the zero-COVID policy in China on December 7, 2022, 57.3% of participants were infected with BA.5 between days 15 and 28 after the first dose, whereas no participants reported having any symptomatic infections between day 3 and day 90 after the second dose. The elevation of nasal nucleocapsid-specific sIgA on days 0, 14, 42, and 118 after the first dose was assessed to verify that these 2-dose participants had no asymptomatic infections.CONCLUSIONA 2-dose intranasal vaccination regimen using NB2155 was safe, was well tolerated, and could dramatically induce broad-spectrum spike-specific sIgA in the nasal passage. Preliminary data suggested that the intranasal vaccination may establish an effective mucosal immune barrier against infection and warranted further clinical studies.TRIAL REGISTRATIONChinese Clinical Trial Registry (ChiCTR2300070346).FUNDINGNatural Science Foundation of China, Guangzhou Laboratory, The First Affiliated Hospital of Guangzhou Medical University.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Inmunidad Mucosa , Inmunoglobulina A Secretora , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adenoviridae , Administración Intranasal , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , COVID-19/prevención & control , COVID-19/inmunología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/efectos adversos , Vectores Genéticos/administración & dosificación , Inmunoglobulina A Secretora/inmunología , Mucosa Nasal/inmunología , Mucosa Nasal/virología , Glicoproteína de la Espiga del Coronavirus/inmunología , Vacunación/métodos
14.
Health Res Policy Syst ; 22(1): 128, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39300562

RESUMEN

BACKGROUND: The article describes attitudes towards vaccinations in Poland in relation to issues such as voluntary versus compulsory vaccinations, the method of financing vaccinations, the method of organizing and carrying out vaccinations, the cognitive and educational aspect of vaccines (how to obtain knowledge about vaccines) and the preferred model of work and research on new vaccines. Taking into account these issues, the authors have created four ideal models of preferred vaccination policies: (a) the market model; (b) the state model; (c) the vaccine hesitancy model; and (d) the civic-social model. This perspective makes it possible to better understand and learn about the various motives behind the attitudes of anti-vaccination movements, as well as to notice cracks and divisions among vaccination supporters and their attitudes towards the financing and organization of vaccinations. METHODS: The study was carried out using the CATI method on a representative random-quota sample of Polish society of 1000 people aged 18 and over. The study took age, sex, education and the size of the place of residence into account. Additionally, in the Socio-demographic factors influencing attitudes towards vaccination practices in Poland section, we used the chi-squared test and regression analysis of factors influencing vaccination practices in Poland. PASW Statistics 18 (a version of SPSS) software was used for statistical analysis. Significant correlations were demonstrated at a significance level of 0.05% Pearson. RESULTS: This article has shown that attitudes towards vaccinations are embedded in broader divisions and orientations related to the vision of the social order: the role of the state, the organization of healthcare and payments for vaccinations and medical services, as well as preferred ways of knowledge production in society and work on new vaccines. The political sympathies and the age of the respondents were the most important variables influencing vaccination behaviour. The education of the respondents was less important. CONCLUSIONS: A few years after the peak of the pandemic, the scope of anti-vaccination attitudes in Polish society ranges from 20% of the population (dogmatic anti-vaxxers) to 30% (vaccine hesitancy occurring depending on attitudes towards vaccinations).


Asunto(s)
COVID-19 , Conocimientos, Actitudes y Práctica en Salud , Vacilación a la Vacunación , Vacunación , Humanos , Polonia , COVID-19/prevención & control , Vacunación/psicología , Masculino , Femenino , Adulto , Persona de Mediana Edad , Vacilación a la Vacunación/psicología , Adulto Joven , Adolescente , Anciano , SARS-CoV-2 , Pandemias , Vacunas contra la COVID-19 , Movimiento Anti-Vacunación/psicología , Política , Encuestas y Cuestionarios , Política de Salud
15.
Cell ; 187(19): 5128-5145, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39303682

RESUMEN

Virology has made enormous advances in the last 50 years but has never faced such scrutiny as it does today. Herein, we outline some of the major advances made in virology during this period, particularly in light of the COVID-19 pandemic, and suggest some areas that may be of research importance in the next 50 years. We focus on several linked themes: cataloging the genomic and phenotypic diversity of the virosphere; understanding disease emergence; future directions in viral disease therapies, vaccines, and interventions; host-virus interactions; the role of viruses in chronic diseases; and viruses as tools for cell biology. We highlight the challenges that virology will face moving forward-not just the scientific and technical but also the social and political. Although there are inherent limitations in trying to outline the virology of the future, we hope this article will help inspire the next generation of virologists.


Asunto(s)
COVID-19 , Virología , Humanos , Virología/historia , COVID-19/virología , COVID-19/epidemiología , SARS-CoV-2/genética , Pandemias , Virus/genética , Virosis/virología , Interacciones Huésped-Patógeno , Historia del Siglo XXI
18.
Front Microbiol ; 15: 1454338, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39309527

RESUMEN

Shigellosis remains a significant global health challenge, particularly in Asia and Africa, where it is a major cause of morbidity and mortality among children. Despite the urgent need, the development of a licensed Shigella vaccine has been hindered, partly due to the lack of suitable animal models for preclinical evaluation. In this study, we used an intragastric adult rhesus macaque challenge model to evaluate the safety, immunogenicity, and efficacy of five live-attenuated Shigella dysenteriae 1 vaccine candidates, all derived from the 1617 parent strain. The vaccine strains included WRSd1, a previously tested candidate with deletions in virG(icsA), stxAB, and fnr, and four other strains-WRSd2, WRSd3, WRSd4, and WRSd5-each containing deletions in virG and stxAB, but retaining fnr. Additionally, WRSd3 and WRSd5 had further deletions in the Shigella enterotoxin gene senA and its paralog senB, with WRSd5 having an extra deletion in msbB2. Rhesus monkeys were immunized three times at two-day intervals with a target dose of 2 × 1010 CFU of the vaccine strains. Thirty days after the final immunization, all monkeys were challenged with a target dose of 2 × 109 CFU of the S. dysenteriae 1 1617 wild-type strain. Safety, immunogenicity, and efficacy were assessed through physical monitoring and the evaluation of immunologic and inflammatory markers following immunization and challenge. Initial doses of WRSd1, WRSd3, and WRSd5 led to mild adverse effects, such as vomiting and loose stools, but all five vaccine strains were well tolerated in subsequent doses. All strains elicited significant IgA and IgG antibody responses, as well as the production of antibody-secreting cells. Notably, none of the vaccinated animals exhibited shigellosis symptoms such as vomiting or loose/watery stool post-challenge, in stark contrast to the control group, where 39% and 61% of monkeys exhibited these symptoms, respectively. The aggregate clinical score used to evaluate Shigella attack rates post-challenge revealed a 72% attack rate in control animals, compared to only 13% in vaccinated animals, indicating a relative risk reduction of 81%. This study highlights the potential of this NHP model in evaluating the safety, immunogenicity, and efficacy of live-attenuated Shigella vaccine candidates, offering a valuable tool for preclinical assessment before advancing to Phase 1 or more advanced clinical trials.

19.
Heliyon ; 10(18): e37634, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39309966

RESUMEN

An excellent technique for producing pharmaceuticals called "molecular farming" enables the industrial mass production of useful recombinant proteins in genetically modified organisms. Protein-based pharmaceuticals are rising in significance because of a variety of factors, including their bioreactivity, precision, safety, and efficacy rate. Heterologous expression methods for the manufacturing of pharmaceutical products have been previously employed using yeast, bacteria, and animal cells. However, the high cost of mammalian cell system, and production, the chance for product complexity, and contamination, and the hurdles of scaling up to commercial production are the limitations of these traditional expression methods. Plants have been raised as a hopeful replacement system for the expression of biopharmaceutical products due to their potential benefits, which include low production costs, simplicity in scaling up to commercial manufacturing levels, and a lower threat of mammalian toxin contaminations and virus infections. Since plants are widely utilized as a source of therapeutic chemicals, molecular farming offers a unique way to produce molecular medicines such as recombinant antibodies, enzymes, growth factors, plasma proteins, and vaccines whose molecular basis for use in therapy is well established. Biopharming provides more economical and extensive pharmaceutical drug supplies, including vaccines for contagious diseases and pharmaceutical proteins for the treatment of conditions like heart disease and cancer. To assess its technical viability and the efficacy resulting from the adoption of molecular farming products, the following review explores the various methods and methodologies that are currently employed to create commercially valuable molecules in plant systems.

20.
World J Methodol ; 14(3): 92344, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39310233

RESUMEN

BACKGROUND: Immunization is a key component of primary health care and an indisputable human right. Vaccines are critical to the prevention and control of infectious disease outbreaks. The coronavirus disease 2019 (COVID-19) pandemic and associated disruptions over the past two years have strained the health systems, with many children missing out on essential childhood vaccines. AIM: To evaluate the immunization coverage among 12-23-month-old children in the rural areas of Community Health Centre (CHC) Dighal and to determine the factors influencing the existing immunization coverage. METHODS: A coverage evaluation survey was conducted according to the 30-cluster sampling technique, which is the standard methodology for such surveys devised by World Health Organization. A total of 300 children aged 12-23 months were included, whose immunization details were noted from their immunization cards. RESULTS: Full immunization rate was noted in 86.7% of the children, with partial and non-immunized children accounting for 9% and 4.3% respectively. The full immunization dropout rate was 4.2%. The common reasons for partial or non-immunization were family problem including illness of mother, vaccine not being available and child being ill. Place of birth (P = 0.014) and availability of immunization card (P < 0.001) were significant predictors of the immunization status. Since the study was conducted in 2020/2021, health services were disrupted due to the COVID-19 lockdown. CONCLUSION: Due to the coverage being higher than the national average, it was concluded that the immunization coverage was optimal and not affected by the COVID-19 pandemic.

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