RESUMO
Targeted drug delivery to the colon offers a myriad of benefits, including treatment of local diseases, direct access to unique therapeutic targets and the potential for increasing systemic drug bioavailability and efficacy. Although a range of traditional colonic delivery technologies are available, these systems exhibit inconsistent drug release due to physiological variability between and within individuals, which may be further exacerbated by underlying disease states. In recent years, significant translational and commercial advances have been made with the introduction of new technologies that incorporate independent multi-stimuli release mechanisms (pH and/or microbiota-dependent release). Harnessing these advanced technologies offers new possibilities for drug delivery via the colon, including the delivery of biopharmaceuticals, vaccines, nutrients, and microbiome therapeutics for the treatment of both local and systemic diseases. This review details the latest advances in colonic drug delivery, with an emphasis on emerging therapeutic opportunities and clinical technology translation.
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Colo/efeitos dos fármacos , Colo/fisiologia , Sistemas de Liberação de Medicamentos/métodos , Produtos Biológicos/administração & dosagem , Preparações de Ação Retardada , Microbioma Gastrointestinal/fisiologia , Trânsito Gastrointestinal/fisiologia , Humanos , Concentração de Íons de Hidrogênio , Síndrome do Intestino Irritável/tratamento farmacológico , Prebióticos/administração & dosagem , Impressão Tridimensional , Probióticos/administração & dosagem , Fatores de Tempo , Vacinas/administração & dosagemRESUMO
BACKGROUND: Haemaphysalis longicornis is an obligate hematophagous ectoparasite that transmits a variety of pathogens causing life-threatening diseases in humans and animals. Paramyosin (Pmy) is not only an invertebrate-specific myofibrillar protein but also an important immunomodulatory protein. Therefore, it is one of the ideal candidate antigens for vaccines. METHODS: We conducted two vaccine trials to evaluate the protective efficacy of Pmy recombinant protein (rPmy) and peptide vaccine (KLH-LEE). Each rabbit was immunized with three doses of rPmy or KLH-LEE adjuvanted with Freund's complete/incomplete at 500 µg/dose at 2-week intervals before challenge with 40 female H. longicornis/rabbit. PBS plus adjuvant, Trx or KLH was used as control group. The antibodies of rabbits were detected by ELISA. Then, female ticks were fed on the rabbits until detachment. RESULTS: ELISA results showed that both vaccines induced rabbits to produce antibodies. Compared with the Trx group, the engorgement weight, oviposition and hatchability of the rPmy group decreased by 8.87%, 26.83% and 38.86%, respectively. On the other hand, engorgement weight, oviposition and hatchability of female ticks in the KLH-LEE group correspondingly resulted in 27.03%, 53.15% and 38.40% reduction compared with that of the KLH group. Considering the cumulative effect of vaccination on the evaluated parameters, results showed 60.37% efficacy of the rPmy vaccine formulation and 70.86% efficacy in the KLH-LEE group. CONCLUSIONS: Pmy and particularly epitope LEE have potential for further development of an effective candidate vaccine to protect the host against tick infection. GRAPHIC ABSTARCT.
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Proteínas de Artrópodes/administração & dosagem , Ixodidae/imunologia , Coelhos/imunologia , Infestações por Carrapato/veterinária , Tropomiosina/administração & dosagem , Vacinas/administração & dosagem , Animais , Anticorpos/sangue , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/imunologia , Avaliação Pré-Clínica de Medicamentos , Feminino , Imunização , Ixodidae/genética , Coelhos/sangue , Coelhos/parasitologia , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Infestações por Carrapato/sangue , Infestações por Carrapato/parasitologia , Infestações por Carrapato/prevenção & controle , Tropomiosina/genética , Tropomiosina/imunologia , Vacinas/genética , Vacinas/imunologia , Vacinas de Subunidades Antigênicas/administração & dosagem , Vacinas de Subunidades Antigênicas/genética , Vacinas de Subunidades Antigênicas/imunologiaRESUMO
In the past two decades, biologic therapy has become ubiquitous in the treatment of psoriasis; however, important considerations should be taken with regard to biologic use in the context of surgery, vaccinations, and cancers. With conflicting evidence on the effects of perioperative biologic use, we recommend withholding tumor necrosis factor alpha (TNF-α) inhibitor therapy for one dose prior to surgical procedures.1 Although no studies have shown a direct link between live vaccines and infection in patients receiving biologics, due to the theoretical risk of live vaccines producing infection in patients with altered immune responses, we recommend withholding biologic therapy for 4 to 5 half-lives prior to the administration of live or live-attenuated vaccines.2,3 Finally, although an increased rate of cancer recurrence has not been demonstrated with biologic use, experts recommend withholding biologic therapy for 2 years after the completion of treatment for invasive cancers and 5 years after the completion of treatment for aggressive malignancies (including melanomas, breast cancers, sarcomas, urinary tract cancers, and myelomas)4; however, exceptions should be considered depending on the patient's circumstances and severity of the psoriasis. (SKINmed. 2021;19:17-0).
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Produtos Biológicos/administração & dosagem , Terapia Biológica/métodos , Psoríase/tratamento farmacológico , Produtos Biológicos/efeitos adversos , Terapia Biológica/efeitos adversos , Humanos , Neoplasias/patologia , Neoplasias/terapia , Assistência Perioperatória/métodos , Psoríase/patologia , Inibidores do Fator de Necrose Tumoral/administração & dosagem , Inibidores do Fator de Necrose Tumoral/efeitos adversos , Vacinas/administração & dosagem , Vacinas/efeitos adversosRESUMO
As one of the most important metabolites of vitamin A, all-trans retinoic acid (RA) plays a crucial role in regulating immune responses. RA has been shown to promote the differentiation of naïve T and B cells and perform diverse functions in the presence of different cytokines. RA also induces gut tropic lymphocytes through upregulating the expression of chemokine (C-C motif) receptor 9 (CCR9) and α4ß7 integrin. In addition, RA promotes the expression of the enzyme retinal dehydrogenase (RALDH) on dendritic cells, which in turn strengthens the ability to synthesize RA. Due to the insolubility of RA, proper formulation design can maximize its ability to improve immune responses for vaccines. Recent studies have developed some formulations co-loading RA and antigen, which can effectively imprint lymphocytes gut homing properties and induce intestine immune responses as well as systemic responses through parenteral administration, providing a promising direction for the protection against mucosal infections. Here, we review the mechanism and effects of RA on lymphocyte differentiation and gut homing, and recent progress of RA delivery systems to improve mucosal immune responses.
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Portadores de Fármacos/química , Imunidade nas Mucosas/efeitos dos fármacos , Enteropatias/prevenção & controle , Tretinoína/administração & dosagem , Vacinas/administração & dosagem , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/química , Animais , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/imunologia , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Modelos Animais de Doenças , Composição de Medicamentos/métodos , Humanos , Imunogenicidade da Vacina , Enteropatias/imunologia , Enteropatias/microbiologia , Mucosa Intestinal/citologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/imunologia , Camundongos , Solubilidade , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Tretinoína/química , Tretinoína/imunologia , Excipientes de Vacinas/química , Vacinas/química , Vacinas/imunologiaRESUMO
PURPOSE: Nasal delivery is a favorable route for vaccination against most respiratory infections, as antigen deposited in the nasal turbinate and Waldeyer's ring areas induce mucosal and systemic immune responses. However, little is known about the nasal distribution of the vaccines, specifically for infants. METHODS: Anatomical nasal replicas of five subjects, 3-24 months, were developed to assess local intranasal vaccine delivery using MAD Nasal™ device, and understand impact of breathing conditions and administration parameters. High performance liquid chromatography was used to quantify the deposition pattern and determine the delivery efficiency. RESULTS: The delivery efficiency on average for all models was found to be 86.57±14.23%. There were no significant differences in the total delivery efficiency between the models in all cases. However, the regional deposition pattern was altered based on the model and subsequent administration. Furthermore, removing the foam tip from the MAD Nasal™ device, to study the impact of insertion length, did not significantly increase the efficiency within the two models tested, 5- and 16-month. CONCLUSION: Incorporating nasal replicas in testing provided a benchmark to determine the efficiency of a common intranasal vaccine delivery combination product. This proposed platform would allow comparing other potential nasal vaccine delivery devices.
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Modelos Anatômicos , Mucosa Nasal/metabolismo , Vacinação/métodos , Vacinas/farmacocinética , Administração Intranasal , Pré-Escolar , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Lactente , Nariz/anatomia & histologia , Nariz/diagnóstico por imagem , Impressão Tridimensional , Tomografia Computadorizada por Raios X , Vacinas/administração & dosagemRESUMO
INTRODUCTION: Given today's increasing calling into question of vaccination, we have studied possible connections between alternative and complementary medical practices (CAM) and vaccine hesitancy (VH) among nurses. METHOD: Ours was a cross-sectional study by self-administered online questionnaire addressed to a panel of nurses in Brittany. After adjustment for other proximal and distal determinants of VH, we examined the impact of CAM use. RESULTS: Multivariate logistic regressions confirmed the existence of a link between CAM and VH. While trust in medical institutions seems to have an important role, CAM use appears largely independent of VH. CONCLUSION: Association between CAM and VH in nurses raises the question not only of their training with respect to these alternative practices, but also of the role of medical institutions in the training of practitioners availing themselves of the latter.
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Terapias Complementares/estatística & dados numéricos , Enfermeiras e Enfermeiros/psicologia , Recusa de Vacinação/estatística & dados numéricos , Vacinação/estatística & dados numéricos , Adolescente , Adulto , Idoso , Estudos Transversais , Feminino , França/epidemiologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Confiança , Vacinas/administração & dosagem , Adulto JovemRESUMO
CpG Oligonucleotides (ODN) are immunomodulatory synthetic oligonucleotides specifically designed to stimulate Toll-like receptor 9. TLR9 is expressed on human plasmacytoid dendritic cells and B cells and triggers an innate immune response characterized by the production of Th1 and pro-inflammatory cytokines. This chapter reviews recent progress in understanding the mechanism of action of CpG ODN and provides an overview of human clinical trial results using CpG ODN to improve vaccines for the prevention/treatment of cancer, allergy, and infectious disease.
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Adjuvantes Imunológicos , Oligodesoxirribonucleotídeos , Vacinas/imunologia , Alérgenos/imunologia , Animais , Biomarcadores , Estudos Clínicos como Assunto , Avaliação Pré-Clínica de Medicamentos , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade , Transdução de Sinais , Receptor Toll-Like 9/metabolismo , Vacinas/administração & dosagem , Vacinas de DNA/genética , Vacinas de DNA/imunologiaRESUMO
BACKGROUND: A rice-based peptide vaccine containing 7 linked human predominant T-cell epitopes (7Crp) derived from Japanese cedar (JC) pollen allergens, Cry j 1 and Cry j 2, was developed. Here, we examined the efficacy and safety of this transgenic rice in JC pollinosis patients. METHODS: Transgenic rice (5, 20, and 80 g) was administered orally. We measured the T-cell proliferative activity against 7Crp, Cry j 1, and Cry j 2; the cytokine expression levels; and specific IgE and IgG4 production levels. In addition, the symptom and medication scores were monitored during the pollen season, and quality of life (QOL) was evaluated. RESULTS: T-cell proliferative activities to Cry j 1, Cry j 2, and 7Crp were significantly depressed in a dose-dependent manner. Oral intake of 80 g transgenic rice for 20 weeks resulted in significant suppression of allergen-specific T-cell proliferation with downregulation of IL-13 and upregulation of IL-10 levels but no changes to specific IgE and IgG4 levels. The QOL symptom scores for allergic rhinitis were not significantly improved. CONCLUSIONS: Allergen-specific T-cell responses were significantly reduced by oral intake of transgenic rice in a dose-dependent manner. However, neither medication score nor QOL symptom scores could be improved during the JC pollen season with oral intake of transgenic rice for 20 weeks.
Assuntos
Alérgenos/imunologia , Antígenos de Plantas/imunologia , Cryptomeria/imunologia , Epitopos de Linfócito T/imunologia , Oryza/imunologia , Pólen/imunologia , Rinite Alérgica Sazonal/prevenção & controle , Administração Oral , Citocinas/metabolismo , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Imunoglobulina G/imunologia , Ativação Linfocitária/imunologia , Plantas Geneticamente Modificadas , Qualidade de Vida , Rinite Alérgica Sazonal/diagnóstico , Rinite Alérgica Sazonal/imunologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Vacinas/administração & dosagem , Vacinas/imunologia , Vacinas de Subunidades Antigênicas/administração & dosagem , Vacinas de Subunidades Antigênicas/imunologiaRESUMO
BACKGROUND: Chronic hepatitis B virus (HBV) infections are a global health problem. There is a need for therapeutic strategies blocking continuous infection of liver cells. The grass pollen allergy vaccine BM32 containing the preS domain of the large HBV surface protein (LHBs) as immunogenic carrier induced IgG antibodies in human subjects inhibiting HBV infection in vitro. Aim of this study was the quantification, epitope mapping and investigation of HBV genotype cross-reactivity of preS-specific antibodies in subjects treated with different dosage regimens of BM32 METHODS: Hundred twenty eight grass pollen allergic patients received in a double-blind, placebo-controlled trial five monthly injections of placebo (aluminum hydroxide, n= 34) or different courses of BM32 (2 placebo + 3 BM32, n= 33; 1 placebo + 4 BM32, n= 30; 5 BM32, n= 31). Recombinant Escherichia coli-expressed preS was purified. Overlapping peptides spanning preS and the receptor-binding sites from consensus sequences of genotypes A-H were synthesized and purified. Isotype (IgM, IgG, IgA, IgE) and IgG subclass (IgG1-IgG4) responses to preS and peptides were determined by ELISA at baseline, one and four months after the last injection. IgG1 and IgG4 subclass concentrations specific for preS and the receptor-binding site were measured by quantitative ELISA. FINDINGS: Five monthly injections induced the highest levels of preS-specific IgG consisting mainly of IgG1 and IgG4, with a sum of median preS-specific IgG1 and IgG4 concentrations of >135 µg/ml reaching up to 1.8 mg/ml. More than 20% of preS-specific IgG was directed against the receptor-binding site. BM32-induced IgG cross-reacted with the receptor-binding domains from all eight HBV genotypes A-H. INTERPRETATION: BM32 induces high levels of IgG1 and IgG4 antibodies against the receptor binding sites of all eight HBV genotypes and hence might be suitable for therapeutic HBV vaccination. FUNDING: This study was supported by the PhD program IAI (KPW01212FW), by Viravaxx AG and by the Danube-ARC funded by the Government of Lower Austria. Rudolf Valenta is a recipient of a Megagrant of the Government of the Russian Federation, grant No 14.W03.31.0024.
Assuntos
Reações Cruzadas/imunologia , Mapeamento de Epitopos , Genótipo , Anticorpos Anti-Hepatite B/genética , Anticorpos Anti-Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/imunologia , Rinite Alérgica Sazonal/prevenção & controle , Vacinas/imunologia , Alérgenos/imunologia , Especificidade de Anticorpos/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Vírus da Hepatite B/imunologia , Hepatite B Crônica/imunologia , Hepatite B Crônica/virologia , Humanos , Esquemas de Imunização , Imunoglobulina E/imunologia , Imunoglobulina G/imunologia , Masculino , Pólen/imunologia , Ligação Proteica , Proteínas Recombinantes/imunologia , Vacinação , Vacinas/administração & dosagemRESUMO
Background: Iron deficiency may impair adaptive immunity and is common among African infants at time of vaccination. Whether iron deficiency impairs vaccine response and whether iron supplementation improves humoral vaccine response is uncertain. Methods: We performed two studies in southern coastal Kenya. In a birth cohort study, we followed infants to age 18 mo and assessed whether anemia or iron deficiency at time of vaccination predicted vaccine response to three-valent oral polio, diphtheria-tetanus-whole cell pertussis-Haemophilus influenzae type b vaccine, ten-valent pneumococcal-conjugate vaccine and measles vaccine. Primary outcomes were anti-vaccine-IgG and seroconversion at age 24 wk and 18 mo. In a randomized trial cohort follow-up, children received a micronutrient powder (MNP) with 5 mg iron daily or a MNP without iron for 4 mo starting at age 7.5 mo and received measles vaccine at 9 and 18 mo; primary outcomes were anti-measles IgG, seroconversion and avidity at age 11.5 mo and 4.5 y. Findings: In the birth cohort study, 573 infants were enrolled and 303 completed the study. Controlling for sex, birthweight, anthropometric indices and maternal antibodies, hemoglobin at time of vaccination was the strongest positive predictor of: (A) anti-diphtheria and anti-pertussis-IgG at 24 wk (p = 0.0071, p = 0.0339) and 18 mo (p = 0.0182, p = 0.0360); (B) anti-pertussis filamentous hemagglutinin-IgG at 24 wk (p = 0.0423); and (C) anti-pneumococcus 19 IgG at 18 mo (p = 0.0129). Anemia and serum transferrin receptor at time of vaccination were the strongest predictors of seroconversion against diphtheria (p = 0.0484, p = 0.0439) and pneumococcus 19 at 18 mo (p = 0.0199, p = 0.0327). In the randomized trial, 155 infants were recruited, 127 and 88 were assessed at age 11.5 mo and 4.5 y. Compared to infants that did not receive iron, those who received iron at time of vaccination had higher anti-measles-IgG (p = 0.0415), seroconversion (p = 0.0531) and IgG avidity (p = 0.0425) at 11.5 mo. Interpretation: In Kenyan infants, anemia and iron deficiency at time of vaccination predict decreased response to diphtheria, pertussis and pneumococcal vaccines. Primary response to measles vaccine may be increased by iron supplementation at time of vaccination. These findings argue that correction of iron deficiency during early infancy may improve vaccine response.
Assuntos
Anemia Ferropriva/imunologia , Suplementos Nutricionais , Ferro/administração & dosagem , Vacinas/administração & dosagem , Anticorpos Antibacterianos/sangue , Anticorpos Antivirais/sangue , Pré-Escolar , Estudos de Coortes , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Imunidade Humoral , Imunoglobulina G/sangue , Lactente , Recém-Nascido , Masculino , VacinaçãoRESUMO
Sentinel surveillance of acute hospitalisations in response to infectious disease emergencies such as the 2009 influenza A(H1N1)pdm09 pandemic is well described, but recognition of its potential to supplement routine public health surveillance and provide scalability for emergency responses has been limited. We summarise the achievements of two national paediatric hospital surveillance networks relevant to vaccine programmes and emerging infectious diseases in Canada (Canadian Immunization Monitoring Program Active; IMPACT from 1991) and Australia (Paediatric Active Enhanced Disease Surveillance; PAEDS from 2007) and discuss opportunities and challenges in applying their model to other contexts. Both networks were established to enhance capacity to measure vaccine preventable disease burden, vaccine programme impact, and safety, with their scope occasionally being increased with emerging infectious diseases' surveillance. Their active surveillance has increased data accuracy and utility for syndromic conditions (e.g. encephalitis), pathogen-specific diseases (e.g. pertussis, rotavirus, influenza), and adverse events following immunisation (e.g. febrile seizure), enabled correlation of biological specimens with clinical context and supported responses to emerging infections (e.g. pandemic influenza, parechovirus, COVID-19). The demonstrated long-term value of continuous, rather than incident-related, operation of these networks in strengthening routine surveillance, bridging research gaps, and providing scalable public health response, supports their applicability to other countries.
Assuntos
Hospitais Pediátricos/estatística & dados numéricos , Programas de Imunização/normas , Admissão do Paciente/estatística & dados numéricos , Vigilância da População/métodos , Vacinação/efeitos adversos , Vacinas/administração & dosagem , Austrália/epidemiologia , Canadá/epidemiologia , Criança , Pré-Escolar , Confiabilidade dos Dados , Política de Saúde , Hospitalização/estatística & dados numéricos , Humanos , Programas Nacionais de Saúde/normas , Vigilância em Saúde Pública , Vacinação/estatística & dados numéricosRESUMO
In an era when the success of the US vaccination policies to date is threatened by vaccine hesitancy, it is important for clinicians to have a working understanding of how vaccines are developed and recommended for use in the United States and how federal and state governments are coordinated to ensure a safe and effective vaccine supply. This article discusses the federal agencies involved in vaccine development and recommendation, other organizations involved in vaccine policy, and the role of vaccine-related public health law in promoting universal vaccination.
Assuntos
Política de Saúde/legislação & jurisprudência , Atenção Primária à Saúde/organização & administração , Vacinas/administração & dosagem , Comitês Consultivos/normas , Movimento contra Vacinação/legislação & jurisprudência , Humanos , Programas Nacionais de Saúde/organização & administração , Segurança do Paciente , Guias de Prática Clínica como Assunto , Atenção Primária à Saúde/normas , Saúde Pública/legislação & jurisprudência , Qualidade da Assistência à Saúde/normas , Estados Unidos , United States Food and Drug Administration/normasRESUMO
Adjuvants improve vaccine potency by enhancing immunogenicity and sustaining long-term immune responses. Lentinan (LNT), a ß-1,3-glucohexaose with ß-1,6-branches, is extracted from the mushroom Lentinus edodes and functions as an effective immunostimulatory drug. Previous studies have demonstrated the adjuvant activity of calcium carbonate (CaCO3) microspheres as well as their use as antigen delivery systems. In this study, we successfully loaded CaCO3 microspheres with LNT and evaluated their physicochemical characteristics prior to the adsorption of ovalbumin. Our experimental results demonstrated that LNT-CaCO3 significantly enhanced lymphocyte proliferation, and boosted the frequency of CD69 + B cells and the ratio of CD4+ to CD8 + T cells in spleen lymphocytes. Moreover, LNT-CaCO3 unexpectedly induced the secretion of IgG and Th-associated cytokines (IL-2, IL-4, IFN-γ, and TNF-α) in immunized mice. Therefore, LNT-CaCO3 microspheres induce robust cellular and humoral immune responses and have potential utility as vaccine delivery systems.
Assuntos
Adjuvantes Imunológicos/administração & dosagem , Carbonato de Cálcio/administração & dosagem , Lentinano/administração & dosagem , Microesferas , Vacinação/métodos , Vacinas/administração & dosagem , Animais , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Citocinas/metabolismo , Feminino , Imunidade Humoral/efeitos dos fármacos , Imunogenicidade da Vacina , Ativação Linfocitária/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/administração & dosagem , Cogumelos Shiitake/química , Baço/efeitos dos fármacos , Baço/imunologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Vacinas/imunologiaRESUMO
The existing vaccine paradigm assumes that vaccines only protect against the target infection, that effective vaccines reduce mortality corresponding to the target infection's share of total mortality, and that the effects of vaccines are similar for males and females. However, epidemiological vaccine research has generated observations that contradict these assumptions and suggest that vaccines have important non-specific effects on overall health in populations. These include the observations that several live vaccines reduce the incidence of all-cause mortality in vaccinated compared with unvaccinated populations far more than can be explained by protection against the target infections, and that several non-live vaccines are associated with increased all-cause mortality in females. In this Personal View we describe current observations and contradictions and define six emerging principles that might explain them. First, that live vaccines enhance resistance towards unrelated infections. Second, non-live vaccines enhance the susceptibility of girls to unrelated infections. Third, the most recently administered vaccination has the strongest non-specific effects. Fourth, combinations of live and non-live vaccines given together have variable non-specific health effects. Fifth, vaccinating children with live vaccines in the presence of maternal immunity enhances beneficial non-specific effects and reduces mortality. Finally, vaccines might interact with other co-administered health interventions, for example vitamin A supplementation. The potential implications for child health are substantial. For example, if BCG vaccination was given to children at birth, if higher measles vaccination coverage could be obtained, if diphtheria, tetanus, and pertussis-containing vaccines were not given with or after measles vaccine, or if the BCG strain with the best non-specific effects could be used consistently, then child mortality could be considerably lower. Pursuing these emerging principles could improve our understanding and use of vaccines globally.
Assuntos
Vacinação , Vacinas/administração & dosagem , Vacinas/imunologia , Criança , Mortalidade da Criança , HumanosRESUMO
Urinary tract infections (UTI) affect half of all women at least once during their lifetime. The rise in the numbers of extended-spectrum beta-lactamase-producing strains and the potential for carbapenem resistance within uropathogenic Escherichia coli (UPEC), the most common causative agent of UTI, create an urgent need for vaccine development. Intranasal immunization of mice with UPEC outer membrane iron receptors FyuA, Hma, IreA, and IutA, conjugated to cholera toxin, provides protection in the bladder or kidneys under conditions of challenge with UPEC strain CFT073 or strain 536. On the basis of these data, we sought to optimize the vaccination route (intramuscular, intranasal, or subcutaneous) in combination with adjuvants suitable for human use, including aluminum hydroxide gel (alum), monophosphoryl lipid A (MPLA), unmethylated CpG synthetic oligodeoxynucleotides (CpG), polyinosinic:polycytidylic acid (polyIC), and mutated heat-labile E. coli enterotoxin (dmLT). Mice intranasally vaccinated with dmLT-IutA and dmLT-Hma displayed significant reductions in bladder colonization (86-fold and 32-fold, respectively), with 40% to 42% of mice having no detectable CFU. Intranasal vaccination of mice with CpG-IutA and polyIC-IutA significantly reduced kidney colonization (131-fold) and urine CFU (22-fold), respectively. dmLT generated the most consistently robust antibody response in intranasally immunized mice, while MPLA and alum produced greater concentrations of antigen-specific serum IgG with intramuscular immunization. On the basis of these results, we conclude that intranasal administration of Hma or IutA formulated with dmLT adjuvant provides the greatest protection from UPEC UTI. This report advances our progress toward a vaccine against uncomplicated UTI, which will significantly improve the quality of life for women burdened by recurrent UTI and enable better antibiotic stewardship.IMPORTANCE Urinary tract infections (UTI) are among the most common bacterial infection in humans, affecting half of all women at least once during their lifetimes. The rise in antibiotic resistance and health care costs emphasizes the need to develop a vaccine against the most common UTI pathogen, Escherichia coli Vaccinating mice intranasally with a detoxified heat-labile enterotoxin and two surface-exposed receptors, Hma or IutA, significantly reduced bacterial burden in the bladder. This work highlights progress in the development of a UTI vaccine formulated with adjuvants suitable for human use and antigens that encode outer membrane iron receptors required for infection in the iron-limited urinary tract.
Assuntos
Administração Intranasal , Proteínas de Escherichia coli/imunologia , Infecções Urinárias/prevenção & controle , Escherichia coli Uropatogênica/imunologia , Vacinas/uso terapêutico , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/farmacologia , Animais , Anticorpos Antibacterianos/sangue , Proteínas da Membrana Bacteriana Externa/imunologia , Vias de Administração de Medicamentos , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/prevenção & controle , Infecções por Escherichia coli/terapia , Feminino , Humanos , Imunização/métodos , Camundongos , Receptores de Superfície Celular/imunologia , Infecções Urinárias/microbiologia , Infecções Urinárias/terapia , Escherichia coli Uropatogênica/patogenicidade , Vacinação/métodos , Vacinas/administração & dosagemRESUMO
INTRODUCTION: Despite the enormous benefits of childhood and maternal immunisation to individual and population health, the uptake of maternal vaccines during pregnancy remains suboptimal. Midwives are a trusted information source for parents and play an important role in the provision of immunisation information. Understanding midwives' attitudes and vaccine knowledge, along with their confidence to discuss maternal and childhood immunisation with parents, is key to reducing parental decisional conflict and achieving immunisation goals. METHODS: An online study was conducted to investigate midwives' knowledge and attitudes towards maternal and childhood vaccination along with their confidence to answer parents' vaccine-related questions. Midwives were recruited by email via the midwifery peek body, the Australian College of Midwives. RESULTS: A total of 359 midwives completed the online survey. The majority of midwives supported maternal (influenza 83%, pertussis 90.5%) and childhood immunisation (85.8%); however, 69.4% of respondents wanted further training about immunisation. Midwives who felt their midwifery education adequately covered immunisation were more confident advising parents about maternal (pâ¯=â¯0.007) and childhood immunisation (pâ¯<â¯0.001). Similarly, Midwives were significantly more likely to confidently advise parents about maternal (pâ¯<â¯0.001) and childhood immunisations (pâ¯<â¯0.001) if they had completed a specific immunisation training course outside of their midwifery course. CONCLUSION: Most midwives working in Australia support vaccination. However, access to contemporary, culturally appropriate education that enables midwives to engage confidently with parents about immunisation is lacking. Education based on a women-centred approach within the pre-registration curriculum along with continuing professional development programs could enable midwives to reduce the evidence to practice gap by increasing vaccine uptake.
Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Tocologia/estatística & dados numéricos , Vacinação/métodos , Vacinas/administração & dosagem , Adolescente , Adulto , Idoso , Atitude do Pessoal de Saúde , Austrália , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tocologia/educação , Pais , Gravidez , Cuidado Pré-Natal/métodos , Inquéritos e Questionários , Adulto JovemRESUMO
Allergen-specific immunotherapy is the only available curative treatment for IgE-mediated allergen diseases. A safe hypoallergenic allergen derivative with high efficiency is required as a tolerogen to induce immune tolerance to the causitive allergens. In this study, to generate a rice-based oral allergy vaccine for Japanese cedar (JC) pollinosis, the tertiary structures of major JC pollen allergens, Cry j 1 and Cry j 2, were more completely destructed by shuffling than the previous ones without losing immunogenicity and then were specifically expressed in the endosperm of transgenic rice seed. They accumulated at high levels and were deposited in endoplasmic reticulum (ER) and ER-derived protein bodies. The low allergenicity of these deconstructed Cry j 1 and Cry j 2 allergens was evaluated by examining their binding activities to the specific IgE antibody and by the basophil degranulation test.
Assuntos
Antígenos de Plantas/imunologia , Cryptomeria/imunologia , Hipersensibilidade/imunologia , Oryza/genética , Plantas Geneticamente Modificadas/genética , Animais , Antígenos de Plantas/genética , Cryptomeria/genética , Humanos , Hipersensibilidade/terapia , Imunoterapia , Camundongos , Oryza/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Pólen/genética , Pólen/imunologia , Ratos , Sementes/genética , Sementes/imunologia , Vacinas/administração & dosagem , Vacinas/genética , Vacinas/imunologiaRESUMO
Aluminium (Al) toxicokinetics after intramuscular (IM) injection of Al-adjuvanted vaccines is unknown. Since animal data are required for modeling and extrapolation, a rat study was conducted measuring Al in plasma and tissues after IM injection of either plain Al-hydroxide (pAH) or Al-phosphate (pAP) adjuvant (Al dose 1.25 mg), single human doses of three Al-adjuvanted vaccines (V1, V2, and V3; Al doses 0.5-0.82 mg), or vehicle (saline). A significant increase in Al plasma levels compared to controls was observed after pAP (AUC(0-80 d), mean ± SD: 2424 ± 496 vs. 1744 ± 508 µg/L*d). Percentage of Al dose released from injected muscle until day 80 was higher after pAP (66.9%) and AP-adjuvanted V3 (85.5%) than after pAH and AH-adjuvanted V1 (0 and 22.3%, resp.). Estimated absolute Al release was highest for pAP (836.8 µg per rat). Al concentration in humerus bone was increased in all groups, again strongest in the pAP group [3.35 ± 0.39 vs. 0.05 ± 0.06 µg/g wet weight (ww)]. Extrapolated amounts in whole skeleton corresponded to 5-12% of the released Al dose. Very low brain Al concentrations were observed in all groups (adjuvant group means 0.14-0.29 µg/g ww; control 0.13 ± 0.04 µg/g ww). The results demonstrate systemically available Al from marketed vaccines in rats being mainly detectable in bone. Al release appears to be faster from AP- than AH-adjuvants. Dose scaling to human adults suggests that increase of Al in plasma and tissues after single vaccinations will be indistinguishable from baseline levels.
Assuntos
Adjuvantes Imunológicos/administração & dosagem , Compostos de Alumínio/administração & dosagem , Hidróxido de Alumínio/administração & dosagem , Fosfatos/administração & dosagem , Vacinas/administração & dosagem , Adjuvantes Imunológicos/farmacocinética , Compostos de Alumínio/farmacocinética , Hidróxido de Alumínio/farmacocinética , Animais , Área Sob a Curva , Humanos , Injeções Intramusculares , Masculino , Fosfatos/farmacocinética , Ratos , Ratos Wistar , Distribuição Tecidual , Vacinas/farmacocinéticaRESUMO
On the subject of vaccination, owing to complex issues connected to vaccine refusal and vaccine hesitancy, the pharmacist is seen as a professional figure in the health sector who is qualified to improve social accountability with the aim of increasing the consent. In order to provide accurate information, Law no. 119/2007 has confirmed the central role of the pharmacist in the promotion of prophylactic vaccination, explicitly stating under art. 2 that the Ministry will be able to count on the collaboration of pharmacists as well as general practitioners and paediatricians. Pharmacists are pinpointed as new professional figures who could assist the national health service in its vaccine awareness and administration campaigns. Art. 5 comma 1 of Law no.119/2017 states that to meet vaccine goals, each Region will be able to allow vaccines to be booked through the Italian booking system (CUP) and administered free-of-charge in authorized pharmacies.