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The SARS-CoV-2 Omicron variant and its sublineages continue to cause COVID-19-associated pediatric hospitalizations, severe disease, and death globally. BNT162b2 and CoronaVac are the main vaccines used in Chile. Much less is known about the Wuhan-Hu-1 strain-based vaccines in the pediatric population compared to adults. Given the worldwide need for booster vaccinations to stimulate the immune response against new Omicron variants of SARS-CoV-2, we characterized the humoral and cellular immune response against Omicron variant BA.1 in a pediatric cohort aged 10 to 16 years who received heterologous vaccination based on two doses of CoronaVac, two doses of CoronaVac (2x) plus one booster dose of BNT162b2 [CoronaVac(2x) + BNT162b2 (1x)], two doses of CoronaVac plus two booster doses of BNT162b2 [CoronaVac(2x) + BNT162b2 (2x)], and three doses of BNT162b2. We observed that the [CoronaVac(2x) + BNT162b2 (2x)] vaccination showed higher anti-S1 and neutralizing antibody titers and CD4 and CD8 T cell immunity specific to the Omicron variant compared to immunization with two doses of CoronaVac alone. Furthermore, from all groups tested, immunity against Omicron was highest in individuals who received three doses of BNT162b2. We conclude that booster vaccination with BNT162b2, compared to two doses of CoronaVac alone, induces a greater protective immunity.
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BACKGROUND: The economic assessment of health care models in palliative care promotes their global development. The purpose of the study is to assess the cost-effectiveness of a palliative care program (named Contigo) with that of conventional care from the perspective of a health benefit plan administrator company, Sanitas, in Colombia. METHODS: The incremental cost-utility ratio (ICUR) and the incremental net monetary benefit (INMB) were estimated using micro-costing in a retrospective, analytical cross-sectional study on the care of terminally ill patients enrolled in a palliative care program. A 6-month time horizon prior to death was used. The EQ-5D-3 L questionnaire (EQ-5D-3 L) and the McGill Quality of Life Questionnaire (MQOL) were used to measure the quality of life. RESULTS: The study included 43 patients managed within the program and 16 patients who received conventional medical management. The program was less expensive than the conventional practice (difference of 1,924.35 US dollars (USD), P = 0.18). When compared to the last 15 days, there is a higher perception of quality of life, which yielded 0.25 in the EQ-5D-3 L (p < 0.01) and 1.55 in the MQOL (P < 0.01). The ICUR was negative and the INMB was positive. CONCLUSION: Because the Contigo program reduces costs while improving quality of life, it is considered to be net cost-saving and a model with value in health care. Greater availability of palliative care programs, such as Contigo, in Colombia can help reduce existing gaps in access to universal palliative care health coverage, resulting in more cost-effective care.
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Análisis Costo-Beneficio , Cuidados Paliativos , Humanos , Colombia , Cuidados Paliativos/economía , Cuidados Paliativos/métodos , Cuidados Paliativos/normas , Análisis Costo-Beneficio/métodos , Masculino , Femenino , Estudios Transversales , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Encuestas y Cuestionarios , Calidad de Vida/psicología , Adulto , Anciano de 80 o más AñosRESUMEN
The development of vaccine adjuvants is of interest for the management of chronic diseases, cancer, and future pandemics. Therefore, the role of Toll-like receptors (TLRs) in the effects of vaccine adjuvants has been investigated. TLR4 ligand-based adjuvants are the most frequently used adjuvants for human vaccines. Among TLR family members, TLR4 has unique dual signaling capabilities due to the recruitment of two adapter proteins, myeloid differentiation marker 88 (MyD88) and interferon-ß adapter inducer containing the toll-interleukin-1 receptor (TIR) domain (TRIF). MyD88-mediated signaling triggers a proinflammatory innate immune response, while TRIF-mediated signaling leads to an adaptive immune response. Most studies have used lipopolysaccharide-based ligands as TLR4 ligand-based adjuvants; however, although protein-based ligands have been proven advantageous as adjuvants, their mechanisms of action, including their ability to undergo structural modifications to achieve optimal immunogenicity, have been explored less thoroughly. In this work, we characterized the effects of two protein-based adjuvants (PBAs) on TLR4 signaling via the recruitment of MyD88 and TRIF. As models of TLR4-PBAs, we used hemocyanin from Fissurella latimarginata (FLH) and a recombinant surface immunogenic protein (rSIP) from Streptococcus agalactiae. We determined that rSIP and FLH are partial TLR4 agonists, and depending on the protein agonist used, TLR4 has a unique bias toward the TRIF or MyD88 pathway. Furthermore, when characterizing gene products with MyD88 and TRIF pathway-dependent expression, differences in TLR4-associated signaling were observed. rSIP and FLH require MyD88 and TRIF to activate nuclear factor kappa beta (NF-κB) and interferon regulatory factor (IRF). However, rSIP and FLH have a specific pattern of interleukin 6 (IL-6) and interferon gamma-induced protein 10 (IP-10) secretion associated with MyD88 and TRIF recruitment. Functionally, rSIP and FLH promote antigen cross-presentation in a manner dependent on TLR4, MyD88 and TRIF signaling. However, FLH activates a specific TRIF-dependent signaling pathway associated with cytokine expression and a pathway dependent on MyD88 and TRIF recruitment for antigen cross-presentation. Finally, this work supports the use of these TLR4-PBAs as clinically useful vaccine adjuvants that selectively activate TRIF- and MyD88-dependent signaling to drive safe innate immune responses and vigorous Th1 adaptive immune responses.
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Factor 88 de Diferenciación Mieloide , Receptor Toll-Like 4 , Humanos , Receptor Toll-Like 4/metabolismo , Factor 88 de Diferenciación Mieloide/metabolismo , Hemocianinas/metabolismo , Streptococcus agalactiae , Ligandos , Proteínas de la Membrana/metabolismo , Adyuvantes de Vacunas , Transducción de Señal , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Adyuvantes Inmunológicos/farmacología , Proteínas Adaptadoras del Transporte Vesicular/metabolismoRESUMEN
Introduction: Severe acute respiratory syndrome virus 2 (SARS-CoV-2) has caused over million deaths worldwide, with more than 61,000 deaths in Chile. The Chilean government has implemented a vaccination program against SARS-CoV-2, with over 17.7 million people receiving a complete vaccination scheme. The final target is 18 million individuals. The most common vaccines used in Chile are CoronaVac (Sinovac) and BNT162b2 (Pfizer-Biotech). Given the global need for vaccine boosters to combat the impact of emerging virus variants, studying the immune response to SARS-CoV-2 is crucial. In this study, we characterize the humoral immune response in inoculated volunteers from Chile who received vaccination schemes consisting of two doses of CoronaVac [CoronaVac (2x)], two doses of CoronaVac plus one dose of BNT162b2 [CoronaVac (2x) + BNT162b2 (1x)], and three doses of BNT162b2 [BNT162b2 (3x)]. Methods: We recruited 469 participants from Clínica Dávila in Santiago and the Health Center Víctor Manuel Fernández in the city of Concepción, Chile. Additionally, we included participants who had recovered from COVID-19 but were not vaccinated (RCN). We analyzed antibodies, including anti-N, anti-S1-RBD, and neutralizing antibodies against SARS-CoV-2. Results: We found that antibodies against the SARS-CoV-2 nucleoprotein were significantly higher in the CoronaVac (2x) and RCN groups compared to the CoronaVac (2x) + BNT162b2 (1x) or BNT162b2 (3x) groups. However, the CoronaVac (2x) + BNT162b2 (1x) and BNT162b2 (3x) groups exhibited a higher concentration of S1-RBD antibodies than the CoronaVac (2x) group and RCN group. There were no significant differences in S1-RBD antibody titers between the CoronaVac (2x) + BNT162b2 (1x) and BNT162b2 (3x) groups. Finally, the group immunized with BNT162b2 (3x) had higher levels of neutralizing antibodies compared to the RCN group, as well as the CoronaVac (2x) and CoronaVac (2x) + BNT162b2 (1x) groups. Discussion: These findings suggest that vaccination induces the secretion of antibodies against SARS-CoV-2, and a booster dose of BNT162b2 is necessary to generate a protective immune response. In the current state of the pandemic, these data support the Ministry of Health of the Government of Chile's decision to promote heterologous vaccination as they indicate that a significant portion of the Chilean population has neutralizing antibodies against SARS-CoV-2.
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COVID-19 , Vacunas , Humanos , Inmunidad Humoral , SARS-CoV-2 , Vacuna BNT162 , Chile , COVID-19/prevención & control , Vacunación , Anticuerpos NeutralizantesRESUMEN
New-generation vaccines, formulated with subunits or nucleic acids, are less immunogenic than classical vaccines formulated with live-attenuated or inactivated pathogens. This difference has led to an intensified search for additional potent vaccine adjuvants that meet safety and efficacy criteria and confer long-term protection. This review provides an overview of protein-based adjuvants (PBAs) obtained from different organisms, including bacteria, mollusks, plants, and humans. Notably, despite structural differences, all PBAs show significant immunostimulatory properties, eliciting B-cell- and T-cell-mediated immune responses to administered antigens, providing advantages over many currently adopted adjuvant approaches. Furthermore, PBAs are natural biocompatible and biodegradable substances that induce minimal reactogenicity and toxicity and interact with innate immune receptors, enhancing their endocytosis and modulating subsequent adaptive immune responses. We propose that PBAs can contribute to the development of vaccines against complex pathogens, including intracellular pathogens such as Mycobacterium tuberculosis, those with complex life cycles such as Plasmodium falciparum, those that induce host immune dysfunction such as HIV, those that target immunocompromised individuals such as fungi, those with a latent disease phase such as Herpes, those that are antigenically variable such as SARS-CoV-2 and those that undergo continuous evolution, to reduce the likelihood of outbreaks.
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In January 2021, the Chilean city of Concepción experienced a second wave of coronavirus 2019 (COVID-19) while in early April 2021, the entire country faced the same situation. This outbreak generated the need to modify and validate a method for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in saliva, thereby expanding the capacity and versatility of testing for COVID-19. This study was conducted in February 2021 in the Chilean city of Concepción during which time, the town was under total quarantine. The study participants were mostly symptomatic (87.4%), not hospitalized, and attended care centers because of their health status rather than being asked by the researchers. People coming to the health center in Concepción to be tested for COVID-19 (via reverse transcriptase polymerase chain reaction [RT-PCR]) from a specimen of nasopharyngeal swab (NPS) were then invited to participate in this study. A total of 131 participants agreed to sign an informed consent and to provide saliva and NPS specimens to validate a method in terms of sensitivity, specificity, and statistical analysis of the cycle threshold (Ct) values from the RT-PCR. Calculations pertaining to the 127 participants who were ultimately included in the analysis showed sensitivity and specificity at 94.34% (95% CI: 84.34-98.82%) and 98.65% (95% CI: 92.70-99.97%), respectively. The saliva specimen showed a performance comparable to NPS as demonstrated by the diagnostic parameters. This RT-PCR method from the saliva specimen is a highly sensitive and specific alternative compared to the reference methodology, which uses the NPS specimen. This modified and validated method is intended for use in the in vitro diagnosis of SARS-CoV-2, which provides health authorities in Chile and local laboratories with a real testing alternative to RT-PCR from NPS.
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COVID-19 , SARS-CoV-2 , Saliva/virología , COVID-19/diagnóstico , Prueba de COVID-19 , Chile , Humanos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , SARS-CoV-2/aislamiento & purificación , Manejo de EspecímenesRESUMEN
BACKGROUND AND OBJECTIVE: In Colombia, older adults (60 years and older) are expected to represent 15.5% of the overall population by 2025. Consequently, the demand for social and healthcare services will increase, especially because of the numerous medical conditions associated with aging. The purpose of the present study was to determine the patient's self-rated health status of older adults with multimorbidity and its determining factors based on gender in an insurance company of the Colombian health system. METHODOLOGY: A cross-sectional study was performed to analyze the sociodemographic and clinical characteristics of 438 patients older than 75 years as well as their self-rated health status (EQ-5D-3L questionnaire) during the first geriatric consultation of a comprehensive healthcare program. A multivariate linear regression analysis was performed to identify factors determining their self-rated health status. RESULTS: Women had a worse self-rated health status than men [mean (standard deviation) EQ-5D index score: 0.77 (0.20) vs. 0.65 (0.18); p<0.001]. In all sample, factors independently associated with self-rated health status were self-perception of weakness and dependency. In men, additional factors related to EQ-5D index were low levels of physical activity, recurrent falls, fecal incontinence, and auditory and visual disorders. In women, other health-determining factors were decrease in walking speed, and a medical history of depression/anxiety. CONCLUSIONS: Factors associated with the self-rated health status of older adults who were part of a comprehensive healthcare program in Colombia varied according to gender. This study will help in approaching health interventions in healthcare programs for older adults in a differentiated manner.
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Estado de Salud , Multimorbilidad , Anciano , Colombia , Estudios Transversales , Femenino , Humanos , Masculino , Calidad de Vida , Encuestas y CuestionariosRESUMEN
In obesity, skeletal muscle mitochondrial activity changes to cope with increased nutrient availability. Autophagy has been proposed as an essential mechanism involved in the regulation of mitochondrial metabolism. Still, the contribution of autophagy to mitochondrial adaptations in skeletal muscle during obesity is unknown. Here, we show that in response to high-fat diet (HFD) feeding, distinct skeletal muscles in mice exhibit differentially regulated autophagy that may modulate mitochondrial activity. We observed that after 4 and 40 weeks of high-fat diet feeding, OXPHOS subunits and mitochondrial DNA content increased in the oxidative soleus muscle. However, in gastrocnemius muscle, which has a mixed fiber-type composition, the mitochondrial mass increased only after 40 weeks of HFD feeding. Interestingly, fatty acid-supported mitochondrial respiration was enhanced in gastrocnemius, but not in soleus muscle after a 4-week HFD feeding. This increased metabolic profile in gastrocnemius was paralleled by preserving autophagy flux, while autophagy flux in soleus was reduced. To determine the role of autophagy in this differential response, we used an autophagy-deficient mouse model with partial deletion of Atg7 specifically in skeletal muscle (SkM-Atg7+/- mice). We observed that Atg7 reduction resulted in diminished autophagic flux in skeletal muscle, alongside blunting the HFD-induced increase in fatty acid-supported mitochondrial respiration observed in gastrocnemius. Remarkably, SkM-Atg7+/- mice did not present increased mitochondria accumulation. Altogether, our results show that HFD triggers specific mitochondrial adaptations in skeletal muscles with different fiber type compositions, and that Atg7-mediated autophagy modulates mitochondrial respiratory capacity but not its content in response to an obesogenic diet.
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Autofagia , Dieta Alta en Grasa , Mitocondrias Musculares/metabolismo , Músculo Esquelético/citología , Animales , Proteína 7 Relacionada con la Autofagia/deficiencia , Proteína 7 Relacionada con la Autofagia/genética , Respiración de la Célula , Ácidos Grasos/metabolismo , Masculino , Ratones , Obesidad/genética , Obesidad/metabolismo , Obesidad/prevención & control , Oxidación-ReducciónRESUMEN
ASBTRACT Objectives Adherence to continuous positive airway pressure (CPAP) devices in patients with obstructive sleep apnea (OSA) determines the effectiveness of the treat-ment. Likewise, the assessment of the control of the disease must consider the information referred by the patient, among other value-based health measures related to the satisfaction of the intervention. The objectives of this study were a) Determine the factors related to adherence to CPAP devices in subjects with OSA affiliated to an insurance company of the healthcare system in Colombia. b) Assess symptom control associated to the disease from the individual's perspective and his/her satisfaction with the treatment received. Materials and Methods 1,501 subjects with OSA were surveyed by telephone to explore: sociodemographic factors, habits and lifestyles, use of CPAP and its adverse events, control of the disease, comorbidities, access to care and therapy satisfaction. Using multilevel logistic regression techniques, the influence of the various factors on adherence to CPAP was analyzed, using Stata 13 software. Results Adherence to CPAP therapy was of 58% and the control of symptoms was of 41.7%. The factors that determined the use of CPAP were knowledge on how the device operates, and the disturbances during sleep due to the mask or nasal pad. The-rapy satisfaction was predominantly very good or good. Conclusion Even with moderate adherence values and a good experience with CPAP therapy, symptomatic control of the disease is poor. Many of the factors that affect the use of CPAP are modifiable with a proper approach by the devices' service provider.
RESUMEN Objetivos La adherencia a los dispositivos de presión positiva continua de la vía aérea (CPAP) en pacientes con síndrome de apnea obstructiva del sueño (SAOS) define la efectividad del tratamiento. Los objetivos de este estudio fueron: a) Determinar los factores relacionados con la adherencia al CPAP en pacientes con SAOS de una aseguradora del Sistema General de Seguridad Social en Salud colombiano y b) evaluar el control de los síntomas de la enfermedad desde la perspectiva del individuo y su satisfacción con la terapia. Materiales y Métodos Mediante encuesta telefónica a 1 501 pacientes con SAOS se exploraron factores sociodemográficos, hábitos y estilos de vida, uso del CPAP y eventos adversos relacionados, control de la enfermedad, comorbilidad, acceso a la atención y satisfacción con la terapia. Utilizando técnicas de regresión logística mul-tinivel, se analizó la influencia de los distintos factores sobre la adherencia al CPAP mediante el software Stata 13. Resultados La adherencia al CPAP fue del 58% y el control de los síntomas del 41,7%. Los factores que determinaron el uso del CPAP fueron el conocimiento del funcionamiento del equipo y la dificultad para dormir debida a la mascarilla o la almohadilla nasal. La satisfacción con la terapia fue buena o muy buena predominantemente. Conclusiones Aún con valores de adherencia moderados y una buena experiencia con la terapia CPAP, el control sintomático de la enfermedad es pobre, pues varios de los factores afectan el uso del CPAP. Dichos factores se pueden intervenir con un adecuado abordaje por parte del prestador de servicios del dispositivo.
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Human metapneumovirus (hMPV) is one of the main pathogens responsible for acute respiratory infections in children up to 5 years of age, contributing substantially to health burden. The worldwide economic and social impact of this virus is significant and must be addressed. The structural components of hMPV (either proteins or genetic material) can be detected by several receptors expressed by host cells through the engagement of pattern recognition receptors. The recognition of the structural components of hMPV can promote the signaling of the immune response to clear the infection, leading to the activation of several pathways, such as those related to the interferon response. Even so, several intrinsic factors are capable of modulating the immune response or directly inhibiting the replication of hMPV. This article will discuss the current knowledge regarding the innate and adaptive immune response during hMPV infections. Accordingly, the host intrinsic components capable of modulating the immune response and the elements capable of restricting viral replication during hMPV infections will be examined.
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Inmunidad Adaptativa , Inmunidad Innata , Metapneumovirus/inmunología , Infecciones por Paramyxoviridae/inmunología , Preescolar , Interacciones Microbiota-Huesped , HumanosRESUMEN
Clinical studies suggest that diabetes is a risk factor in the development of pulmonary arterial hypertension. The increase in blood pressure in the pulmonary area is characterized by the increase in the afterload and hypertrophy of the right ventricle. The objective of this study was to conduct a longitudinal follow-up of the morphological and functional changes in the right ventricle in a rat model with pulmonary arterial hypertension secondary to diabetes. Male Sprague Dawley rats were randomly divided into a control group (saline solution) and a diabetic group (60 mg/kg with streptozotocin). For 12 weeks, an echocardiography for longitudinal (in vivo) image analysis of the pulmonary pressure was performed at the same time as the evaluation of myocardial remodeling and right ventricular. After this period, the pulmonary pressure was measured by means of a pulmonary artery catheterization, and the presence of hypertrophy was determined by means of the Fulton index. The plasma concentration of brain natriuretic peptide was measured by means of the ELISA technique. It was found that the diabetic rats showed an increase in pressure in the pulmonary arteries, an increase in the Fulton index, and an increase in brain natriuretic peptide. The echocardiographic follow-up showed that the diabetic rats presented an increase in the pulmonary artery from the fourth week, while hypertrophy and right ventricular systolic dysfunction occurred until the twelfth week. In conclusion, pulmonary arterial hypertension induced by experimental diabetes generated hypertrophy and systolic dysfunction of the right ventricle.
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Ecocardiografía , Ventrículos Cardíacos/diagnóstico por imagen , Hipertensión Pulmonar/diagnóstico por imagen , Animales , Glucemia/metabolismo , Presión Sanguínea/fisiología , Peso Corporal , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Experimental/fisiopatología , Diástole/fisiología , Estudios de Seguimiento , Insuficiencia Cardíaca/fisiopatología , Frecuencia Cardíaca/fisiología , Ventrículos Cardíacos/fisiopatología , Hipertensión Pulmonar/sangre , Hipertensión Pulmonar/fisiopatología , Masculino , Péptido Natriurético Encefálico/metabolismo , Ratas Sprague-Dawley , Factores de Riesgo , Estreptozocina , Sístole/fisiología , Remodelación Vascular/fisiologíaRESUMEN
BACKGROUND: Group B Streptococcus (GBS) is the leading cause of invasive neonatal infection. In this study, we aimed to evaluate the analytical validation of qualitative real-time polymerase chain reaction (qPCR) as a means to detect GBS. METHODS: Genomic DNA (gDNA) was purified from 12 ATCC bacterial strains, two belonging to GBS and the remainder acting as negative controls. Additionally, gDNA was isolated from 21 strains of GBS from various serotypes (Ia, Ib and II-VIII). All gDNA was used to evaluate the analytical validation of the qPCR method employing a specific Taqman probe. Inclusivity, exclusivity, anticipated reportable range, the limit of detection and robustness were evaluated. The methods used are described in international guidelines and other existing reports. The performance of this qPCR method for detecting GBS was compared to other microbiological methods used with vaginal-rectal samples from pregnant women. RESULTS: Our qPCR method for detecting GBS was analytically validated. It has a limit of detection of 0.7 GE/µL and 100% analytical specificity. It detects all strains of GBS with the same level of performance as microbiological methods. CONCLUSION: Data suggest that this qPCR method performs adequately as a means to detect GBS in vaginal-rectal swabs from pregnant women.
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Complicaciones Infecciosas del Embarazo/microbiología , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Infecciones Estreptocócicas/microbiología , Streptococcus agalactiae/aislamiento & purificación , ADN Bacteriano/aislamiento & purificación , Femenino , Humanos , Embarazo , Recto/microbiología , Sensibilidad y Especificidad , Streptococcus agalactiae/genética , Vagina/microbiologíaRESUMEN
Group B Streptococcus (GBS) is the primary etiological agent of sepsis and meningitis in newborns and is associated with premature birth and stillbirth. The development of a licensed vaccine is one of the pending challenges for the World Health Organization. Previously, we showed that oral immunization with surface immune protein (SIP) decreases vaginal colonization of GBS and generates functional opsonizing antibodies, which was determined by opsonophagocytic assays (OPA) in vitro. We also showed that the protein has an adjuvant vaccine profile. Therefore, an oral vaccine based on SIP may be an attractive alternative to employ in the development of new vaccines against GBS. Lactococcus lactis is a highlighted oral vaccine probiotic inducer of the mucosal immune response. This bacterium could serve as an antigen-delivering vehicle for the development of an edible vaccine and has been used in clinical trials. In this study, we showed that an oral vaccine with a recombinant L. lactis strain secreting SIP from GBS (rL. lactis-SIP) can induce protective humoral and cellular immunity in an experimental model of GBS vaginal colonization in C57BL/6 mice. Mice immunized with rL. lactis-SIP were protected against clinical symptoms and bacterial colonization after GBS vaginal colonization. Our rL. lactis-SIP vaccine also induces an increase of immunoglobulin G (IgG) and immunoglobulin A (IgA) specifically against SIP. The adoptive transfer of serum from vaccinated mice to naïve mice generated protection against GBS vaginal colonization. Moreover, the rL. lactis-SIP strain induces the activation of SIP-specific T cells, which could decrease GBS vaginal colonization and generate protective antibodies when transferred to other mice. Our experimental observations strongly support the notion that rL. lactis-SIP induces protective humoral and cellular immunity and could be considered as a novel alternative in the development of vaccines for GBS.
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Vaccine-induced protection against pathogens, especially subunit-based vaccines, are related to antigen properties but mainly in their ability to stimulate the immune system by the use of an adjuvant. Modern vaccines are formulated with a high level of antigen purity, where an efficient adjuvant is necessary. In this context, the use of protein Toll-Like Receptor (TLR) agonists as vaccine adjuvants has been highlighted because of their optimal immunogenicity and minimal toxicity. The Surface Immunogenic Protein (SIP) from Group B Streptococcus (GBS) has gained importance as a new potential protein-based vaccine. Recently, we reported that recombinant SIP (rSIP) expressed by E. coli and purified by High Performance Liquid Chromatography (HPLC) alone induces a protective humoral immune response. In this study, we present the immunomodulatory properties of rSIP as a protein-based adjuvant, as an agonist of TLR. To this end, we showed that C57BL/6 bone marrow-derived dendritic cells pulsed by rSIP resulted in enhanced CD40, CD80, CD86, and Major Histocompatibility Complex (MHC) class II as well as increased secretion proinflammatory cytokines Interleukin (IL)-6, Interferon (IFN)-γ, Tumor Necrosis Factor (TNF)-α, and IL-10. Next, we investigated the in vivo effect of rSIP in the absence or presence of ovalbumin (OVA) on antigen-specific antibody secretion in C57BL/6 mice. Immunization with rSIP plus OVA showed that anti-OVA IgG2a and IgG1a increased significantly compared with OVA alone in C57BL/6 mice. Also, the immunization of rSIP plus OVA generates increased serum cytokines levels characterized by IL-12p70, IL-10, IL-4, and IFN-γ. Interestingly, we observed that rSIP stimulate Toll Like Receptor (TLR)2 and TLR4, individually expressed by Human embryonic kidney (HEK) 293-derived TLR reporter cells. These findings suggest that rSIP is a new potential protein TLR agonist adjuvant and may be employed in the development of new vaccines.
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The Bacillus Calmette-Guérin (BCG) is a live attenuated tuberculosis vaccine that has the ability to induce non-specific cross-protection against pathogens that might be unrelated to the target disease. Vaccination with BCG reduces mortality in newborns and induces an improved innate immune response against microorganisms other than Mycobacterium tuberculosis, such as Candida albicans and Staphylococcus aureus. Innate immune cells, including monocytes and natural killer (NK) cells, contribute to this non-specific immune protection in a way that is independent of memory T or B cells. This phenomenon associated with a memory-like response in innate immune cells is known as "trained immunity." Epigenetic reprogramming through histone modification in the regulatory elements of particular genes has been reported as one of the mechanisms associated with the induction of trained immunity in both, humans and mice. Indeed, it has been shown that BCG vaccination induces changes in the methylation pattern of histones associated with specific genes in circulating monocytes leading to a "trained" state. Importantly, these modifications can lead to the expression and/or repression of genes that are related to increased protection against secondary infections after vaccination, with improved pathogen recognition and faster inflammatory responses. In this review, we discuss BCG-induced cross-protection and acquisition of trained immunity and potential heterologous effects of recombinant BCG vaccines.
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Inmunidad Adaptativa , Vacuna BCG/inmunología , Protección Cruzada/inmunología , Mycobacterium tuberculosis/inmunología , Tuberculosis/inmunología , Tuberculosis/prevención & control , Animales , Vacuna BCG/administración & dosificación , Interacciones Huésped-Patógeno , Humanos , Inmunomodulación , Mycobacterium bovis/inmunología , Vacunación , Vacunología/métodosRESUMEN
Group B Streptococcus (GBS) represents one of the most common causes of bacterial infection in neonates; it is also associated with premature childbirth and stillbirth. A vaccine against GBS is needed, but no approved vaccines are yet available. The Surface Immunogenic Protein (SIP) of GBS is conserved in all serotypes and had been reported to be a good vaccine prototype in a mouse model of GBS infection. Also, we have previously shown that both subcutaneous and oral immunization with rSIP can induce an efficient immune response that decreases GBS vaginal colonization in mice. In this study, we show that a vaccine based on a mixture of rSIP and AbISCO-100 adjuvant reduces GBS vaginal colonization in mice and induces antibodies with opsonophagocytic activities. Moreover, the passive transfer of sera and total T-cells from mice immunized with rSIP mixed with AbISCO-100 to unvaccinated mice decreases vaginal GBS colonization in an infected mouse. This is the first report of cellular immunity associated with rSIP-based vaccine testing in a mouse model of GBS infection.
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Formación de Anticuerpos/inmunología , Inmunidad Celular/inmunología , Infecciones Estreptocócicas/inmunología , Streptococcus/crecimiento & desarrollo , Adyuvantes Inmunológicos/farmacología , Animales , Anticuerpos Antibacterianos/inmunología , Vacunas Bacterianas/inmunología , Femenino , Inmunización/métodos , Ratones , Ratones Endogámicos C57BL , Vacunación/métodosRESUMEN
The human respiratory syncytial virus (hRSV) is the main etiologic agent of severe lower respiratory tract infections that affect young children throughout the world, associated with significant morbidity and mortality, becoming a serious public health problem globally. Up to date, no licensed vaccines are available to prevent severe hRSV-induced disease, and the generation of safe-effective vaccines has been a challenging task, requiring constant biomedical research aimed to overcome this ailment. Among the difficulties presented by the study of this pathogen, it arises the fact that there is no single animal model that resembles all aspects of the human pathology, which is due to the specificity that this pathogen has for the human host. Thus, for the study of hRSV, different animal models might be employed, depending on the goal of the study. Of all the existing models, the murine model has been the most frequent model of choice for biomedical studies worldwide and has been of great importance at contributing to the development and understanding of vaccines and therapies against hRSV. The most notable use of the murine model is that it is very useful as a first approach in the development of vaccines or therapies such as monoclonal antibodies, suggesting in this way the direction that research could have in other preclinical models that have higher maintenance costs and more complex requirements in its management. However, several additional different models for studying hRSV, such as other rodents, mustelids, ruminants, and non-human primates, have been explored, offering advantages over the murine model. In this review, we discuss the various applications of animal models to the study of hRSV-induced disease and the advantages and disadvantages of each model, highlighting the potential of each model to elucidate different features of the pathology caused by the hRSV infection.
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OBJECTIVE: To analyze the emergency hospitalizations trend for ambulatory care sensitive conditions between 2011 and 2015 in a health insureance company of the Colombian Social Security General System. METHODS: A log-linear analysis based on age-adjusted hospitalization rates for ambulatory care sensitive conditions in the Entidad Promotora de Salud Sanitas was used to estimate the annual percentage change in these rates and to identify joinponts of the rates. Data was collected from administrative sources. RESULTS: There were 38,530 hospitalizations for ambulatory care sensitive conditions in 26,501 Entidad Promotora de Salud Sanitas enrollees, with a significant decrease in hospitalization rates. The annual percentage change estimated for the period was -9.5% with no significant joinpoints throughout the time interval. CONCLUSIONS: A significant reduction in hospital admissions due to ambulatory care sensitive conditions in Entidad Promotora de Salud Sanitas enrollees were reported for the last five years in this study.
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Atención Ambulatoria/estadística & datos numéricos , Tratamiento de Urgencia/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Enfermedad Aguda , Adolescente , Adulto , Distribución por Edad , Anciano , Atención Ambulatoria/tendencias , Niño , Enfermedad Crónica , Colombia/epidemiología , Tratamiento de Urgencia/tendencias , Femenino , Hospitalización/tendencias , Humanos , Masculino , Persona de Mediana Edad , Atención Primaria de Salud/estadística & datos numéricos , Atención Primaria de Salud/tendencias , Estudios Retrospectivos , Factores de Tiempo , Adulto JovenRESUMEN
The aim of this study was to evaluate the cost derived from the hospitalization of people living with HIV (PLHIV) in Colombia between 2011 and 2015. This is an analysis of the direct cost of PLHIV hospitalization from the perspective of an insurer of the Colombian General Social Security System. The costs were calculated in Colombian pesos and corrected for inflation on the basis of the 2017 Consumer Price Index of the Bank of the Republic of Colombia. It was converted to US dollars at the Market Representative Exchange Rate of the same year. We analyzed 1129 hospitalizations in 612 PLHIV, of which 12% started with a diagnosis of HIV during the same hospitalization, with the majority in the AIDS stage (63%). The median overall cost of hospitalizations was US$1509 (25th and 75th percentiles: US$711-US$3254), being even higher in patients with AIDS and as the CD4 T lymphocyte count decreased. The cost derived from the medical care of PLHIV increases as the clinical control of the disease worsens, and it is a key indicator of the impact of the strategies implemented for the timely identification of the infection and subsequent management of the disease.
Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Infecciones por VIH/tratamiento farmacológico , Costos de la Atención en Salud/estadística & datos numéricos , Hospitalización/economía , Aseguradoras , Infecciones Oportunistas Relacionadas con el SIDA/economía , Infecciones Oportunistas Relacionadas con el SIDA/mortalidad , Adulto , Colombia/epidemiología , Costo de Enfermedad , Análisis Costo-Beneficio/estadística & datos numéricos , Costos y Análisis de Costo , Femenino , Infecciones por VIH/economía , Infecciones por VIH/mortalidad , Humanos , Masculino , Persona de Mediana EdadRESUMEN
ABSTRACT OBJECTIVE To analyze the emergency hospitalizations trend for ambulatory care sensitive conditions between 2011 and 2015 in a health insureance company of the Colombian Social Security General System. METHODS A log-linear analysis based on age-adjusted hospitalization rates for ambulatory care sensitive conditions in the Entidad Promotora de Salud Sanitas was used to estimate the annual percentage change in these rates and to identify joinponts of the rates. Data was collected from administrative sources. RESULTS There were 38,530 hospitalizations for ambulatory care sensitive conditions in 26,501 Entidad Promotora de Salud Sanitas enrollees, with a significant decrease in hospitalization rates. The annual percentage change estimated for the period was -9.5% with no significant joinpoints throughout the time interval. CONCLUSIONS A significant reduction in hospital admissions due to ambulatory care sensitive conditions in Entidad Promotora de Salud Sanitas enrollees were reported for the last five years in this study.