RESUMEN
Management of the exposure of pediatric oncology patients to varicella zoster virus (VZV) is controversial. We report the exposure of 56 patients to a single child with chicken pox at a pediatric cancer housing facility and describe our strategic approach for their management. We reviewed the immune and clinical status of 56 children with cancer receiving ongoing treatment at Memorial Sloan Kettering Cancer Center (MSK) who, while living at a pediatric cancer housing facility, were exposed to the index patient. The management of patients exposed included: (1) determination of immune status, (2) availability of vaccination history or VZV disease prophylaxis, (3) exposure status and subsequent isolation during the period of incubation, and (4) VZV disease prophylaxis. In addition to the 56 patients exposed to the index case, eight children with cancer treated at other facilities and 11 healthy siblings living in the facility were exposed. Of the 56 MSK patients, 21 were classified as immunosuppressed and received varicella zoster immune globulin (human), intravenous standard immune globulin, or acyclovir based on serostatus and immune function. The cohort was followed for 4 weeks after the exposure and no secondary infections were diagnosed. We performed a risk assessment and created a management plan to control and prevent further exposure and development of disease. No secondary cases developed. This strategic approach could serve as a model for the management of VZV exposure for other pediatric oncology centers.
Asunto(s)
Herpesvirus Humano 3 , Neoplasias , Humanos , Niño , Femenino , Masculino , Preescolar , Herpesvirus Humano 3/inmunología , Adolescente , Neoplasias/terapia , Lactante , Varicela/prevención & control , Aciclovir/uso terapéutico , Huésped Inmunocomprometido , Antivirales/uso terapéutico , Sueros Inmunes/administración & dosificaciónRESUMEN
SUMMARY: In response to the threat posed by new variants of SARS-CoV-2 and the urgent need for effective treatments in the absence of vaccines, the aim of this study was to develop a rapid and cost-effective hyperimmune serum (HS) derived from sheep and assess its efficacy. The utilization of a halal-certified, easily maintained in certain geographic regions, easy-to-handle animal such as sheep could provide a viable alternative to the expensive option of horses. Sheep were immunized with a whole inactivated SARS-CoV- 2 antigen to produce HS, which was evaluated for neutralizing potency using the PRNT50 assay. K18-hACE2 transgenic mice (n=35) were divided into three groups: control, SARS-CoV-2 exposure through inhalation, and SARS-CoV-2 exposed mice treated with HS. HS efficacy was assessed through serum proinflammatory cytokine levels, qRT-PCR analysis, histopathological examination of lungs and hearts, and transmission electron microscopy. Purified HS exhibited significant neutralizing activity (1/24,576). The SARS-CoV-2+HS group showed lower levels of TNF-α, IL-10, and IL-6 (P<0.01) and relatively lower levels of MCP-1 compared to the SARS-CoV-2 group. HS prevented death, reduced viral RNA levels in the lungs and hearts, protected against severe interstitial pneumonia, preserved lung tissue integrity, and prevented myocyte damage, while the SARS-CoV-2 group exhibited viral presence in the lungs. This study successfully developed a sheep-derived HS against the entire SARS-CoV-2 virus, resulting in a significant reduction in infection severity, inflammation, and systemic cytokine production. The findings hold promise for treating severe COVID-19 cases, including emerging viral variants, and immunocompromised patients.
En respuesta a la amenaza que suponen las nuevas variantes del SARS-CoV-2 y la urgente necesidad de tratamientos eficaces en ausencia de vacunas, el objetivo de este estudio fue desarrollar un suero hiperinmune (HS) rápido y rentable derivado de ovejas. y evaluar su eficacia. La utilización de un animal con certificación halal, de fácil mantenimiento en determinadas regiones geográficas y de fácil manejo, como las ovejas, podría proporcionar una alternativa viable a la costosa opción de los caballos. Las ovejas fueron inmunizadas con un antígeno de SARS-CoV-2 completamente inactivado para producir HS, cuya potencia neutralizante se evaluó mediante el ensayo PRNT50. Los ratones transgénicos K18-hACE2 (n = 35) se dividieron en tres grupos: control, exposición al SARS-CoV-2 mediante inhalación y ratones expuestos al SARS-CoV-2 tratados con HS. La eficacia de HS se evaluó mediante niveles de citoquinas proinflamatorias en suero, análisis qRT-PCR, examen histopatológico de pulmones y corazones y microscopía electrónica de transmisión. El HS purificado exhibió una actividad neutralizante significativa (1/24,576). El grupo SARS-CoV-2+HS mostró niveles más bajos de TNF-α, IL-10 e IL-6 (P<0,01) y niveles relativamente más bajos de MCP-1 en comparación con el grupo SARS-CoV-2. HS evitó la muerte, redujo los niveles de ARN viral en los pulmones y el corazón, protegió contra la neumonía intersticial grave, preservó la integridad del tejido pulmonar y evitó el daño de los miocitos, mientras que el grupo SARS-CoV-2 exhibió presencia viral en los pulmones. Este estudio desarrolló con éxito un HS derivado de ovejas contra todo el virus SARS-CoV-2, lo que resultó en una reducción significativa de la gravedad de la infección, la inflamación y la producción sistémica de citocinas. Los hallazgos son prometedores para el tratamiento de casos graves de COVID- 19, incluidas las variantes virales emergentes y los pacientes inmunocomprometidos.
Asunto(s)
Animales , COVID-19/tratamiento farmacológico , Sueros Inmunes/administración & dosificación , Sistema Respiratorio/efectos de los fármacos , Sistema Respiratorio/ultraestructura , Ovinos , Vacunas de Productos Inactivados , Síndrome Respiratorio Agudo Grave/prevención & control , Microscopía Electrónica de Transmisión , Reacción en Cadena en Tiempo Real de la Polimerasa , Citometría de Flujo , SARS-CoV-2/efectos de los fármacos , COVID-19/inmunología , COVID-19/prevención & control , Corazón/efectos de los fármacos , Caballos , Inmunoterapia/métodos , Insuficiencia Multiorgánica/prevención & control , Miocardio/ultraestructuraRESUMEN
Reproductive techniques such as superovulation and in vitro fertilisation (IVF) have been widely used in generating genetically modified animals. The current gold standard for superovulation in mice is using coherent treatments of equine chorionic gonadotropin (eCG) and human chorionic gonadotropin (hCG). An alternative method using inhibin antiserum (IAS) instead of eCG has been recently reported. Here, we evaluate different superovulation strategies in C57BL/6J and B6D2F1 mice. Firstly, we found that using 5-week-old C57BL/6J and 4-week-old B6D2F1 donors could achieve better superovulation outcomes. Then, we compared eCG-hCG, IAS-hCG and eCG-IAS-hCG with different dosages in both mouse strains. Significantly increased numbers of oocytes were obtained by using IAS-hCG and eCG-IAS-hCG methods. However, low fertilisation rates (36.3-38.8%) were observed when natural mating was applied. We then confirmed that IVF could dramatically ameliorate the fertilisation rates up to 89.1%. Finally, we performed CRISPR-Cas9 mediated genome editing targeting Scn11a and Kcnh1 loci, and successfully obtained mutant pups using eCG-hCG and IAS-hCG induced zygotes, which were fertilised by either natural mating or IVF. Our results showed that IAS is a promising superovulation reagent, and the efficiency of genome editing is unlikely to be affected by using IAS-induced zygotes.
Asunto(s)
Proteína 9 Asociada a CRISPR , Edición Génica/métodos , Superovulación , Animales , Gonadotropina Coriónica/administración & dosificación , Canales de Potasio Éter-A-Go-Go/genética , Femenino , Fertilización In Vitro/métodos , Sueros Inmunes/administración & dosificación , Inhibinas/inmunología , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Canal de Sodio Activado por Voltaje NAV1.9/genéticaRESUMEN
As dogs experience oestrus only once or twice a year, it is necessary to establish an effective method of oestrous induction for efficient breeding. In the present study, we evaluated inhibin antiserum (IAS) on oestrous induction in anoestrous females. Bitches were administered 0.5 ml/kg IAS or a mixture of 50 IU/kg equine chorionic gonadotropin (eCG) and 0.5 ml/kg IAS and 500 IU human chorionic gonadotropin (hCG) administered 7 days after the mixture injection. As a control, bitches received 50 IU/kg eCG, with 500 IU hCG administered 7 days after eCG injection. Blood-tinged vaginal discharge, vulvar swelling, plasma progesterone concentrations and ovarian follicular development were assessed from day 0 to day 14. IAS alone injection did not induce oestrus in bitches at the anoestrous stage. Conversely, vulvar swelling, blood-tinged vaginal discharge and an estimated luteinizing hormone (LH) surge appeared on days 3-7, days 3-6 and days 7-9 after the IAS+eCG mixture injection, respectively, in all five bitches at the anoestrous stage. The average number of developing and ovulated follicles in bitches administered IAS+eCG was 8.8 and 9.6 respectively. A single eCG injection followed by hCG induced oestrous signs, with an average of 8.3 developing follicles and 4.5 ovulated follicles. This study revealed that IAS alone did not induce oestrus, but when IAS was used in combination with eCG, it induced oestrus and promoted a considerable number of ovulations in anoestrous dogs.
Asunto(s)
Gonadotropinas Equinas/farmacología , Sueros Inmunes/administración & dosificación , Inhibinas/inmunología , Inducción de la Ovulación/veterinaria , Animales , Gonadotropina Coriónica/farmacología , Perros , Estro/efectos de los fármacos , Femenino , Inducción de la Ovulación/métodosRESUMEN
The role of nontreponemal antibodies in the Treponema pallidum infection course is unclear. We investigated the effect of immunization with nontreponemal antigen on T. pallidum-challenged rabbits. Nontreponemal antigen was injected intravenously into rabbits in the nontreponemal group (n = 12) to elicit antibodies (≥1:64), and normal saline-injected rabbits were used as controls (n = 12). Then, rabbits were challenged with 106T. pallidum per site along their back. Lesion development was observed, and the injection sites were biopsied for mRNA analysis every week. Six rabbits from both groups were euthanized at 14 d and 28 d. The popliteal lymph nodes were extracted to assess infectivity using a rabbit infectivity test. The maximum lesion diameters were not different between the two groups (12.4 ± 0.9 mm in the nontreponemal group vs. 12.5 ± 1.0 mm in the control group, P = 0.386), but the time to maximum diameter appearance was delayed by approximately 4 d in the nontreponemal group (14.4 ± 1.6 d vs. 10.8 ± 1.9 d, P = 0.000). There were no significant differences in the proportions of lesions (58/60 (96.7%) vs. 59/60 (98.3%), P = 0.500) or ulcers (55/60 (91.7%) vs. 57/60 (95.0%), P = 0.359) between the two groups. An ulcer development delay of 5 d was observed in the nontreponemal group (19.3 ± 2.0 d vs. 14.0 ± 1.8 d, P = 0.000). IL-2 and IFN-γ mRNA expression in the nontreponemal group was significantly higher than that in the control group at 7 d and 14 d post-challenge. flaA mRNA expression and the rabbit infectivity test positive rate were not different between the two groups. Immunization with nontreponemal antigen altered the syphilis course in rabbits, resulting in delayed maximal lesion diameter and ulcer development, but it could not inhibit the spread of T. pallidum from primary lesion sites to viscera.
Asunto(s)
Antígenos Bacterianos/inmunología , Sueros Inmunes/inmunología , Inmunización/métodos , Sífilis/prevención & control , Treponema pallidum/inmunología , Administración Intravenosa , Animales , Anticuerpos Antibacterianos/biosíntesis , Antígenos Bacterianos/administración & dosificación , Citocinas/efectos de los fármacos , Citocinas/metabolismo , Modelos Animales de Enfermedad , Flagelina/sangre , Flagelina/efectos de los fármacos , Flagelina/genética , Humanos , Sueros Inmunes/administración & dosificación , Inyecciones Intradérmicas , Hígado/efectos de los fármacos , Hígado/microbiología , Ganglios Linfáticos/trasplante , Masculino , Conejos , Enfermedades Cutáneas Infecciosas/microbiología , Enfermedades Cutáneas Infecciosas/prevención & control , Bazo/efectos de los fármacos , Bazo/microbiología , Sífilis/sangre , Testículo/efectos de los fármacos , Testículo/microbiología , Treponema pallidum/efectos de los fármacos , Úlcera/microbiología , Úlcera/prevención & controlRESUMEN
Anti-CD20 monoclonal antibodies are widely used for the treatment of hematological malignancies or autoimmune disease but may be responsible for a secondary humoral deficiency. In the context of COVID-19 infection, this may prevent the elicitation of a specific SARS-CoV-2 antibody response. We report a series of 17 consecutive patients with profound B-cell lymphopenia and prolonged COVID-19 symptoms, negative immunoglobulin G (IgG)-IgM SARS-CoV-2 serology, and positive RNAemia measured by digital polymerase chain reaction who were treated with 4 units of COVID-19 convalescent plasma. Within 48 hours of transfusion, all but 1 patient experienced an improvement of clinical symptoms. The inflammatory syndrome abated within a week. Only 1 patient who needed mechanical ventilation for severe COVID-19 disease died of bacterial pneumonia. SARS-CoV-2 RNAemia decreased to below the sensitivity threshold in all 9 evaluated patients. In 3 patients, virus-specific T-cell responses were analyzed using T-cell enzyme-linked immunospot assay before convalescent plasma transfusion. All showed a maintained SARS-CoV-2 T-cell response and poor cross-response to other coronaviruses. No adverse event was reported. Convalescent plasma with anti-SARS-CoV-2 antibodies appears to be a very promising approach in the context of protracted COVID-19 symptoms in patients unable to mount a specific humoral response to SARS-CoV-2.
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Anticuerpos Antivirales/inmunología , Linfocitos B/patología , Betacoronavirus/inmunología , Infecciones por Coronavirus/inmunología , Sueros Inmunes/administración & dosificación , Linfopenia/terapia , Neumonía Viral/inmunología , Adulto , Anciano , Linfocitos B/inmunología , Transfusión de Componentes Sanguíneos , COVID-19 , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/terapia , Infecciones por Coronavirus/virología , Femenino , Francia , Neoplasias Hematológicas/complicaciones , Humanos , Inmunización Pasiva , Linfopenia/etiología , Linfopenia/patología , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/sangre , Neumonía Viral/terapia , Neumonía Viral/virología , SARS-CoV-2 , Sueroterapia para COVID-19RESUMEN
Post-exposure prophylaxis (PEP) with varicella zoster immunoglobulins (VZIG) should be administered as soon as possible after exposure to the virus, but always within ten days; in the previous guidelines this was within 96 hours. In cases of perinatal exposure, PEP with VZIG should be administered to neonates if the mother develops clinical chickenpox between seven days before delivery and seven days after delivery; in the previous guidelines this was between five days before delivery and two days after delivery. A new chapter on the treatment of chickenpox has been added to the guidelines.
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Varicela/prevención & control , Herpes Zóster/prevención & control , Sueros Inmunes/administración & dosificación , Profilaxis Posexposición/métodos , Varicela/transmisión , Femenino , Herpes Zóster/transmisión , Herpesvirus Humano 3 , Humanos , Recién Nacido , Masculino , Madres , Guías de Práctica Clínica como Asunto , Embarazo , Factores de RiesgoAsunto(s)
Infecciones por Coronavirus/terapia , Sueros Inmunes/administración & dosificación , Plasma/inmunología , Neumonía Viral/inmunología , Neumonía Viral/terapia , Betacoronavirus , COVID-19 , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/inmunología , Brotes de Enfermedades/prevención & control , Humanos , Inmunización Pasiva , Pandemias , Neumonía Viral/diagnóstico , Neumonía Viral/epidemiología , SARS-CoV-2 , Tratamiento Farmacológico de COVID-19 , Sueroterapia para COVID-19RESUMEN
Recently, Zika virus (ZIKV) has become more widespread, thus attracting global attention. The vaccine against Japanese encephalitis virus (JEV) is currently used in China, being included in planned immunisation regimes. Although ZIKV and JEV are closely related mosquito-borne Flaviviruses, and a complex cross-immune response within flaviviruses has been demonstrated, the effect of JEV vaccination on ZIKV infection has not been well described. Thus, this study aimed to explore the impact of different titres of anti-JEV antibodies (Abs) against ZIKV infection using sera from healthy human donors in Guangzhou and anti-JEV rabbit polyclonal antibodies (pAbs) in vitro and vivo. Human anti-JEV Ab titres were tested at decreasing concentrations as the age increased. A neutralising effect on ZIKV infection was observed when anti-JEV Ab titres in human sera or rabbit pAbs were high (the corresponding age was under 30 years). Even though a lower titre in human sera showed no apparent effect, whereas rabbit pAbs had an antibody-dependent enhancement(ADE)effect, we proved an ADE effect in vivo for the first time. This study suggests that individuals over 60 years of age are at high risk for JEV and ZIKV infection, and screening this age group for infection should strengthen. Furthermore, a deep exploration of the relationship between anti-JEV Abs and ZIKV infection is needed.
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Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Virus de la Encefalitis Japonesa (Especie)/inmunología , Encefalitis Japonesa/inmunología , Sueros Inmunes/inmunología , Infección por el Virus Zika/inmunología , Virus Zika/inmunología , Adolescente , Adulto , Animales , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Acrecentamiento Dependiente de Anticuerpo , Niño , Preescolar , Chlorocebus aethiops , Protección Cruzada , Reacciones Cruzadas , Encefalitis Japonesa/prevención & control , Femenino , Humanos , Sueros Inmunes/administración & dosificación , Sueros Inmunes/sangre , Lactante , Células K562 , Masculino , Ratones Endogámicos C57BL , Persona de Mediana Edad , Pruebas de Neutralización , Conejos , Vacunación , Células Vero , Adulto JovenRESUMEN
There are inconsistencies in how newborns are managed following exposure to varicella, ranging from reassurance and observation to administration of varicella zoster immunoglobulin (VZIG) and admission to hospital for varying length courses of intravenous aciclovir.Hospitalised preterm babies exposed to varicella should receive VZIG. Administration can otherwise be limited to pregnant non-immune women or to newborns if there is development of maternal chickenpox from 5 days prior to delivery up to 48 hours postdelivery. Intravenous aciclovir is only recommended in cases of newborn disease despite VZIG or in severe disease. The use of VZIG may not prevent varicella but may reduce severity of disease.In this article, we review the evidence for risk to non-immune mothers, the fetus and newborns who had different types of exposure to varicella, with recommendations for management and treatment of confirmed neonatal chickenpox.
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Aciclovir/administración & dosificación , Antivirales/administración & dosificación , Varicela/prevención & control , Sueros Inmunes/administración & dosificación , Complicaciones Infecciosas del Embarazo/prevención & control , Adulto , Femenino , Humanos , Recién Nacido , Recien Nacido Prematuro , EmbarazoRESUMEN
Rabies continues to poses serious threats to the public health in many countries. The development of novel inexpensive, safe and effective vaccines has become a high priority for rabies control worldwide. We previously generated a novel recombinant rabies vaccine by cloning rabies virus glycoprotein into a chimpanzee adenoviral vector, termed ChAd68-Gp. The present study evaluated the immune responses and protection afforded by this vaccine in beagle dogs. The results demonstrated that intramuscular immunization with both low-dose and high-dose of ChAd68-Gp induced strong immune responses and provided complete protection in beagles even at low-dose. However, when administered orally, high-dose vaccination was protective while low-dose vaccination was ineffective. Further investigation indicated that the low-pH value of gastric juice in the stomach of beagles might decompose the adenovirus. Therefore, suitable formulation for adenovirus-based oral vaccine should be considered and developed. The chimpanzee adenovirus-vectored rabies vaccine ChAd68-Gp warrants extensive test for clinical application.
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Adenovirus de los Simios/genética , Anticuerpos Neutralizantes/biosíntesis , Anticuerpos Antivirales/biosíntesis , Vacunas Antirrábicas/administración & dosificación , Virus de la Rabia/efectos de los fármacos , Rabia/prevención & control , Proteínas del Envoltorio Viral/administración & dosificación , Adenovirus de los Simios/inmunología , Administración Oral , Animales , Perros , Femenino , Vectores Genéticos/química , Vectores Genéticos/inmunología , Concentración de Iones de Hidrógeno , Sueros Inmunes/administración & dosificación , Inyecciones Intramusculares , Masculino , Ratones , Ratones Endogámicos BALB C , Rabia/mortalidad , Rabia/patología , Rabia/virología , Vacunas Antirrábicas/genética , Vacunas Antirrábicas/inmunología , Virus de la Rabia/genética , Virus de la Rabia/inmunología , Virus de la Rabia/patogenicidad , Análisis de Supervivencia , Vacunación/métodos , Vacunas Sintéticas , Proteínas del Envoltorio Viral/genética , Proteínas del Envoltorio Viral/inmunologíaRESUMEN
INTRODUCTION: Despite vaccination, there were more than 100,000 annual cases of varicella in the United States in 2013-2014. Individuals at highest risk of developing severe or complicated varicella include immunocompromised people, preterm infants, and pregnant women. Varicella zoster immune globulin (human) (VARIZIG) is recommended by the CDC for postexposure prophylaxis to prevent or attenuate varicella-zoster virus infection in high-risk individuals. Contemporary information on administration of VARIZIG is limited. METHODS: This open-label, expanded-access program provided VARIZIG to physician-identified, high-risk participants exposed to varicella. Participants included immunocompromised children/adults, infants (preterm, newborns whose mothers had varicella onset within 5 days before or 2 days after delivery, and those aged <1 year), and pregnant women. VARIZIG (125 IU/10 kg [up to 625 IU]) was administered intramuscularly, ideally within 96 hours, but up to 10 days, postexposure. Incidence of varicella rash and severity (>100 pox, pneumonia, or encephalitis) were assessed up to 42 days after administration. RESULTS: The varicella outcome population (n = 507) included 263 immunocompromised participants (32 adults, 231 children), 137 pregnant women, 105 infants, and 2 healthy adults with no history of varicella. Varicella incidence was 4.5% in immunocompromised participants, 7.3% in pregnant women, and 11.5% in infants. The incidence of varicella was similar when comparing VARIZIG administration ≤ 96 hours vs > 96 hours (up to 10 days) postexposure in the entire population (6.2% vs. 9.4%, respectively), and also in each subgroup. Of 34 participants with varicella, 5 developed > 100 pox and 1 developed pneumonia and encephalitis. There were no product-related deaths and only 1 serious adverse event (serum sickness) considered probably related to VARIZIG. CONCLUSION: Postexposure administration of VARIZIG was associated with low rates of varicella in high-risk participants, regardless of when administered within 10 days postexposure. VARIZIG was well-tolerated and safe in high-risk participants.
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Varicela/inmunología , Varicela/prevención & control , Sueros Inmunes/administración & dosificación , Huésped Inmunocomprometido , Recien Nacido Prematuro , Femenino , Humanos , Sueros Inmunes/efectos adversos , Lactante , Recién Nacido , Masculino , EmbarazoRESUMEN
Preexisting immunity against dengue virus or West Nile virus was previously reported to mediate antibody-dependent enhancement (ADE) of Zika virus (ZIKV) infection in a mouse model. We show here that ZIKV-immune plasma samples from both symptomatic and asymptomatic individuals mediated ZIKV ADE of infection in vitro and in mice. In a lethal infection model with a viral inoculum 10 times higher, both ADE and protection were observed, depending on the amount of infused immune plasma. In a vertical-transmission model, ZIKV-immune plasma infused to timed pregnant mice increased fetal demise and decreased the body weight of surviving fetuses. Depletion of IgG from an immune plasma abolished ADE of infection, and the presence of purified IgG alone mediated ADE of infection. Higher viral loads and proinflammatory cytokines were detected in mice treated with ZIKV-immune plasma samples compared to those receiving control plasma. Together, these data show that passive immunization with homotypic ZIKV antibodies, depending on the concentration, could either worsen or limit a subsequent ZIKV infection.IMPORTANCE Antibody-dependent enhancement (ADE) of virus infection is common to many viruses and is problematic when plasma antibody levels decline to subneutralizing concentrations. ADE of infection is especially important among flaviviruses, many of which are the cause of global health problems. Recently, human plasma samples immune to heterologous flaviviruses were shown to promote Zika virus (ZIKV) infection. Here we showed in immunocompromised mouse models that homologous immune plasma samples protect mice from subsequent infection at high antibody concentrations but that they mediate ADE of infection and increase ZIKV pathogenesis in adult mice and fetal demise during pregnancy at low concentrations.
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Acrecentamiento Dependiente de Anticuerpo , Sueros Inmunes/administración & dosificación , Sueros Inmunes/efectos adversos , Infección por el Virus Zika/inmunología , Infección por el Virus Zika/fisiopatología , Virus Zika/inmunología , Adulto , Animales , Anticuerpos Antivirales/administración & dosificación , Anticuerpos Antivirales/efectos adversos , Modelos Animales de Enfermedad , Humanos , Ratones , Modelos Teóricos , Carga Viral , Infección por el Virus Zika/prevención & controlRESUMEN
Superovulation technique is important to improve the efficiency of oocyte and animal production and reduce the number of oocyte donors. Previously, we have reported that the coadministration of inhibin antiserum (IAS) and equine chorionic gonadotropin (eCG) results in the production of >100 oocytes in a 4-week-old female C57BL/6 mice. It is well established that superovulation depends on the age of the female mice. However, detailed data regarding the ovulation of juvenile, mature, and aged female mice following the administration of IAS and eCG as well as the performance of reproductive technologies using oocytes have not yet been investigated. In the present study, we examined the effect of the age of female mice (3-50 weeks old) on the number of ovulated oocytes via the coadministration of IAS and eCG or eCG alone. Treatment with IAS plus eCG produced the maximum number of oocytes at 4 weeks of age. Moreover, IAS plus eCG produced more oocytes than eCG alone in mice aged between 3 and 5 weeks or 7 and 30 weeks. The fertilization and birth rates were similar between the two treatments at any age. Moreover, after vitrifying and warming the embryos, the survival and birth rates of two-cell embryos were similar between the two treatments. Subsequently, we examined the optimal ages of female mice (between 24 and 34 days) to obtain a high and stable number of oocytes. In mice aged between 24 and 32 days, IAS plus eCG induced the production of more eggs than eCG alone. Notably, the coadministration of IAS and eCG in mice aged between 25 and 31 days resulted in stable ovulation and high number of oocytes. Using the tip of the optimal female aged between 25 and 31 days old, we demonstrated an efficient production of embryos and offspring between homozygous knockout males and few females aged 26-28 days via in-vitro fertilization and embryo transfer. In summary, the coadministration of IAS and eCG resulted in a higher number of oocytes in juvenile, mature, and aged female mice. This treatment may be useful for the efficient production of homozygous mutant mice from a limited number of female mice.
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Gonadotropina Coriónica/farmacología , Sueros Inmunes/farmacología , Inhibinas/antagonistas & inhibidores , Superovulación/efectos de los fármacos , Envejecimiento , Animales , Gonadotropina Coriónica/administración & dosificación , Criopreservación , Quimioterapia Combinada , Técnicas de Cultivo de Embriones , Femenino , Fertilización In Vitro , Sueros Inmunes/administración & dosificación , Masculino , Ratones , Ratones Endogámicos C57BL , Oocitos/fisiologíaRESUMEN
Epstein-Barr virus (EBV) causes infectious mononucleosis and is associated with epithelial-cell cancers and B cell lymphomas. An effective EBV vaccine is not available. We found that antibodies to the EBV glycoprotein gH/gL complex were the principal components in human plasma that neutralized infection of epithelial cells and that antibodies to gH/gL and gp42 contributed to B cell neutralization. Immunization of mice and nonhuman primates with nanoparticle vaccines that displayed components of the viral-fusion machinery EBV gH/gL or gH/gL/gp42 elicited antibodies that potently neutralized both epithelial-cell and B cell infection. Immune serum from nonhuman primates inhibited EBV-glycoprotein-mediated fusion of epithelial cells and B cells and targeted an epitope critical for virus-cell fusion. Therefore, unlike the leading EBV gp350 vaccine candidate, which only protects B cells from infection, these EBV nanoparticle vaccines elicit antibodies that inhibit the virus-fusion apparatus and provide cell-type-independent protection from virus infection.
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Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Linfocitos B/inmunología , Células Epiteliales/inmunología , Infecciones por Virus de Epstein-Barr/prevención & control , Herpesvirus Humano 4/inmunología , Glicoproteínas de Membrana/inmunología , Proteínas del Envoltorio Viral/inmunología , Animales , Linfocitos B/virología , Células CHO , Fusión Celular , Línea Celular Tumoral , Cricetulus , Células Epiteliales/virología , Infecciones por Virus de Epstein-Barr/inmunología , Femenino , Células HEK293 , Células HeLa , Humanos , Sueros Inmunes/administración & dosificación , Macaca fascicularis , Masculino , Ratones , Ratones Endogámicos BALB C , Vacunas de Partículas Similares a Virus/inmunología , Vacunas Virales/inmunología , Acoplamiento ViralRESUMEN
Helicobacter pylori (H. pylori) urease is a key protein for persistent infection of the bacteria in the stomach. Although H. pylori generally induce anti-H. pylori-specific antibodies (Abs), these Abs do not usually work for eradication or prevention of the H. pylori infection. In our previous study, we identified a linear epitope composed of 19-mer peptides termed UB-33, CHHLDKSIKEDVQFADSRI, within the large subunit of H. pylori urease. Anti-UB-33-specific Abs neutralized the enzymatic activity of H. pylori urease in vitro. In the present study, we evaluated the effect of immunization of BALB/c mice with H. pylori UB-33 peptide. After confirming the production of anti-UB-33-specific Abs, mice were challenged orally with H. pylori Sydney Strain-1 (SS-1). Mice producing anti-UB-33-specific Abs were not infected with SS-1, and the amount of SS-1 isolate in their stomach was significantly reduced. Also, the urease-negative mutant of H. pylori, HPP1801, did not colonize in the stomach, indicating that H. pylori urease was a critical element for infection of H. pylori in the gastric mucosa. Moreover, mice producing UB-33-specific Abs apparently suppressed H. pylori infection in the stomach where anti-UB-33 Abs were secreted in the gastric juice, indicating that H. pylori colonization was inhibited in the presence of anti-UB-33 Abs. In addition, the neutralization activity of sera from mice immunized with purified urease was less potent than that in the sera from mice immunized with UB-33. Furthermore, the recognition of epitope UB-33 was mediated through Toll-like receptor 2 (TLR2) on the B-1 cells using TLR2-knockout BALB/c mice in vivo. These results indicate that liner peptide UB-33 should be used for immunization to induce neutralizing Abs instead of purified H. pylori urease to prevent H. pylori infection and their colonization in the stomach.
Asunto(s)
Anticuerpos Antibacterianos/biosíntesis , Anticuerpos Neutralizantes/biosíntesis , Proteínas Bacterianas/inmunología , Infecciones por Helicobacter/prevención & control , Inmunización/métodos , Péptidos/inmunología , Ureasa/inmunología , Secuencia de Aminoácidos , Animales , Proteínas Bacterianas/genética , Epítopos/química , Epítopos/inmunología , Femenino , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/inmunología , Mucosa Gástrica/microbiología , Eliminación de Gen , Expresión Génica , Infecciones por Helicobacter/genética , Infecciones por Helicobacter/inmunología , Infecciones por Helicobacter/microbiología , Helicobacter pylori/efectos de los fármacos , Helicobacter pylori/crecimiento & desarrollo , Helicobacter pylori/inmunología , Sueros Inmunes/administración & dosificación , Ratones , Ratones Endogámicos BALB C , Péptidos/administración & dosificación , Péptidos/síntesis química , Estómago/efectos de los fármacos , Estómago/inmunología , Estómago/microbiología , Receptor Toll-Like 2/genética , Receptor Toll-Like 2/inmunología , Ureasa/deficiencia , Ureasa/genéticaRESUMEN
Immunization of mice with recombinant IgA1 protease of Neisseria meningitidis or several structural derivatives thereof protects the animals infected with a variety of deadly pathogens, including N. meningitidis serogroups A, B, and C and 3 serotypes of Streptococcus pneumonia. In sera of rabbits immunized with inactivated pneumococcal cultures, antibodies binding IgA1-protease from N. meningitidis serogroup B were detected. Thus, the cross-reactive protection against meningococcal and pneumococcal infections has been demonstrated in vivo. Presumably it indicates the presence of common epitopes in the N. meningitidis IgA1 protease and S. pneumoniae surface proteins.
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Infecciones Meningocócicas/prevención & control , Vacunas Meningococicas/inmunología , Neisseria meningitidis/inmunología , Infecciones Neumocócicas/prevención & control , Proteínas Recombinantes/inmunología , Serina Endopeptidasas/inmunología , Streptococcus pneumoniae/inmunología , Animales , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Protección Cruzada , Femenino , Sueros Inmunes/administración & dosificación , Sueros Inmunes/inmunología , Infecciones Meningocócicas/inmunología , Vacunas Meningococicas/administración & dosificación , Ratones Endogámicos BALB C , Neisseria meningitidis/enzimología , Infecciones Neumocócicas/inmunología , Conejos , Serina Endopeptidasas/química , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/inmunologíaRESUMEN
Anthrax is primarily recognized as an affliction of herbivores with incubation period ranging from three to five days post-infection. Currently, the Sterne live-spore vaccine is the only vaccine approved for control of the disease in susceptible animals. While largely effective, the Sterne vaccine has several problems including adverse reactions in sensitive species, ineffectiveness in active outbreaks and incompatibility with antibiotics. These can be surmounted with the advent of recombinant peptides (non-living) next generation vaccines. The candidate vaccine antigens comprised of recombinant protective antigen (PA), spore-specific antigen (bacillus collagen-like protein of anthracis, BclA) and formaldehyde inactivated spores (FIS). Presently, little information exists on the protectivity of these novel vaccine candidates in susceptible ruminants. Thus, this study sought to assess the immunogenicity of these vaccine candidates in goats and evaluate their protectivity using an in vivo mouse model. Goats receiving a combination of PA, BclA and FIS yielded the highest antibody and toxin neutralizing titres compared to recombinant peptides alone. This was also reflected in the passive immunization experiment whereby mice receiving immune sera from goats vaccinated with the antigen combination had higher survival post-challenge. In conclusion, the current data indicate promising potential for further development of non-living anthrax vaccines in ruminants.
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Enfermedades de los Animales/prevención & control , Vacunas contra el Carbunco/inmunología , Carbunco/inmunología , Antígenos Bacterianos/inmunología , Sueros Inmunes/inmunología , Proteínas Recombinantes/inmunología , Animales , Vacunas contra el Carbunco/administración & dosificación , Anticuerpos Antibacterianos/inmunología , Cabras , Sueros Inmunes/administración & dosificación , Inmunidad Humoral/inmunología , Ratones , Esporas Bacterianas/inmunologíaRESUMEN
Visceral leishmaniasis, the most severe form of leishmaniasis, is caused by Leishmania donovani and L. infantum. Immunity to Leishmania infection has been shown to depend on the development of Th1 cells; however, the roles of B cells and antibodies during infection remain unclear. In the present study, we showed that AID and µs double-deficient mice (DKO), which have B cells but not circulating immunoglobulins (cIgs), became resistant to L. donovani infection, whereas µs or AID single-deficient mice did not. This resistance in DKO mice occurred in the liver from an early stage of the infection. The depletion of IFN-γ did not affect the rapid reduction of parasite burden, whereas NADPH oxidases was up-regulated in the livers of infected DKO mice. The inhibition of the reactive oxygen species pathway in vivo by apocynin, a NADPH oxidase inhibitor, resulted in a significant increase in the parasite burden in DKO mice. These results indicate that a circulating Ig deficiency induces a protective response against L. donovani infection by elevating IFN-γ-independent NADPH oxidase activity, and also that cIgs play a regulatory role in controlling L. donovani infection in mice.
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Citidina Desaminasa/genética , Resistencia a la Enfermedad/genética , Cadenas mu de Inmunoglobulina/genética , Leishmania donovani/inmunología , Leishmaniasis Visceral/inmunología , Especies Reactivas de Oxígeno/inmunología , Animales , Linfocitos B/inmunología , Linfocitos B/parasitología , Citidina Desaminasa/deficiencia , Citidina Desaminasa/inmunología , Activación Enzimática , Femenino , Regulación de la Expresión Génica , Genes Reporteros , Sueros Inmunes/administración & dosificación , Inmunización Pasiva/métodos , Cadenas mu de Inmunoglobulina/sangre , Cadenas mu de Inmunoglobulina/inmunología , Interferón gamma/genética , Interferón gamma/inmunología , Leishmania donovani/patogenicidad , Leishmaniasis Visceral/genética , Leishmaniasis Visceral/parasitología , Luciferasas/genética , Luciferasas/metabolismo , Ratones , Ratones Noqueados , NADPH Oxidasas/genética , NADPH Oxidasas/inmunología , Carga de Parásitos , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal , Células TH1/inmunología , Células TH1/parasitologíaRESUMEN
It is widely accepted that live vaccines elicit higher immune protection than inactivated vaccines. However, the mechanisms are largely unknown. Here, an array with 64 recombinant outer membrane proteins of Vibrio parahemolyticus was developed to explore antibody responses of live and inactivated V. parahemolyticus post immunization of the 8th, 12th, 16th and 20th day. Among the 64 outer membrane proteins, 28 elicited antibody generation. They were all detected in live vaccine-induced immunity but only 15 antibodies were found in inactivated vaccine-induced immunity. Passive immunization showed that higher percent survival was detected in live than inactivated vaccine-induced immunities. Active immunization indicated that out of 19 randomly selected outer membrane proteins, 5 stimulated immune protection against V. parahemolyticus infection. Among them, antibodies to VP2309 and VPA0526 were shared in mice immunized by live or inactivated vaccines, whereas antibodies to VPA0548, VPA1745, and VP1667 were only found in mice immunized by live vaccine. In addition, live V. parahemolyticus stimulated earlier antibody response than inactivated bacteria. These results indicate that not all of the outer membrane proteins elicited antibody responses when they work together in the form of live or inactivated bacteria; live vaccine elicits more protective antibodies, which contribute to higher immune protection in live vaccine than inactivated vaccine. Notably, the recombinant proteins might be different from those separated from live bacteria, and they might be different in their immunogenic potencies.