RESUMEN
Crohn's disease is a chronic inflammatory disease of the gastrointestinal tract. Immunosuppressive therapy is the main treatment modality in Crohn's disease. Herpes zoster (HZ), caused by Varicella-zoster virus, is a relatively common albeit burdensome clinical picture mainly affecting adult population with immunosuppressive status. In this paper, we aimed to report a Crohn's disease patient with HZ to raise awareness on vaccination. There are commercially available vaccines that are shown to be safe and effective against HZ reactivation. Crohn's disease patients should be evaluated and informed about preventive options against HZ to prevent unwanted HZ-related complications.
Asunto(s)
Enfermedad de Crohn , Herpes Zóster , Humanos , Herpes Zóster/prevención & control , Vacunación , Herpesvirus Humano 3/inmunología , Adulto , Vacuna contra el Herpes Zóster/administración & dosificación , Vacuna contra el Herpes Zóster/inmunología , Masculino , FemeninoRESUMEN
Vaccinations are effective in preventing infections; however, it is unknown if patients with chronic lymphocytic leukemia (CLL) who are treatment naïve (TN) or receiving Bruton tyrosine kinase inhibitors (BTKi's) respond to novel adjuvanted vaccines. Understanding the effect of BTKi's on humoral immunity is timely because BTKi's are widely used and vaccination against coronavirus disease 2019 is urgently needed. In 2 open-label, single-arm clinical trials, we measured the effect of BTKi's on de novo immune response against recombinant hepatitis B vaccine (HepB-CpG) and recall response against recombinant zoster vaccine (RZV) in CLL patients who were TN or on BTKi. The primary end point was serologic response to HepB-CpG (anti-hepatitis B surface antibodies ≥10 mIU/mL) and RZV (≥fourfold increase in anti-glycoprotein E). The response rate to HepB-CpG was lower in patients on BTKi (3.8%; 95% confidence interval [CI], 0.7-18.9) than patients who were TN (28.1%; 95% CI, 15.6-45.4; P = .017). In contrast, the response rate to RZV did not differ significantly between the BTKi (41.5%; 95% CI, 27.8-56.6) and TN cohorts (59.1%; 95% CI, 38.7-76.7; P = .2). BTKi's were associated with a decreased de novo immune response following HepB-CpG, whereas recall immune response following RZV was not significantly affected by BTKi therapy. These trials were registered at www.clinicaltrials.gov as #NCT03685708 (Hep-CpG) and #NCT03702231 (RZV).
Asunto(s)
Vacunas contra Hepatitis B/inmunología , Vacuna contra el Herpes Zóster/inmunología , Inmunidad , Leucemia Linfocítica Crónica de Células B/inmunología , Inhibidores de Proteínas Quinasas/efectos adversos , Vacunas Sintéticas/inmunología , Adyuvantes Inmunológicos , Agammaglobulinemia Tirosina Quinasa/antagonistas & inhibidores , Anciano , Femenino , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Evaluación del Resultado de la Atención al Paciente , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , VacunaciónRESUMEN
BACKGROUND: Vaccine adjuvants are compounds that significantly enhance/prolong the immune response to a co-administered antigen. The limitations of the use of aluminium salts that are unable to elicite cell responses against intracellular pathogens such as those causing malaria, tuberculosis, or AIDS, have driven the development of new alternative adjuvants such as QS-21, a triterpene saponin purified from Quillaja saponaria. PURPOSE: The aim of this review is to attempt to clarify the mechanism of action of QS-21 through either receptors or signaling pathways in vitro and in vivo with special emphasis on the co-administration with other immunostimulants in new adjuvant formulations, called adjuvant systems (AS). Furthermore, the most relevant clinical applications will be presented. METHODS: A literature search covering the period 2014-2018 was performed using electronic databases from Sci finder, Science direct, Medline/Pubmed, Scopus, Google scholar. RESULTS: Insights into the mechanism of action of QS-21 can be summarized as follows: 1) in vivo stimulation of Th2 humoral and Th1 cell-mediated immune responses through action on antigen presenting cells (APCs) and T cells, leading to release of Th1 cytokines participating in the elimination of intracellular pathogens. 2) activation of the NLRP3 inflammasome in mouse APCs with subsequent release of caspase-1 dependent cytokines, Il-1ß and Il-18, important for Th1 responses. 3) synthesis of nearly 50 QS-21 analogs, allowing structure/activity relationships and mechanistic studies. 4) unique synergy mechanism between monophosphoryl lipid A (MPL A) and QS-21, formulated in a liposome (AS01) in the early IFN-γ response, promoting vaccine immunogenicity. The second part of the review is related to phase I-III clinical trials of QS-21, mostly formulated in ASs, to evaluate efficacy, immunogenicity and safety of adjuvanted prophylactic vaccines against infectious diseases, e.g. malaria, herpes zoster, tuberculosis, AIDS and therapeutic vaccines against cancer and Alzheimer's disease. CONCLUSION: The most advanced phase III clinical applications led to the development of two vaccines containing QS-21 as part of the AS, the Herpes Zoster vaccine (HZ/su) (Shingrix™) which received a license in 2017 from the FDA and a marketing authorization in the EU in 2018 and the RTS,S/AS01 vaccine (Mosquirix™) against malaria, which was approved by the EMA in 2015 for further implementation in Sub-Saharan countries for routine use.
Asunto(s)
Adyuvantes Inmunológicos/farmacología , Vacuna contra el Herpes Zóster/inmunología , Inmunidad Celular/efectos de los fármacos , Lípido A/análogos & derivados , Vacunas contra la Malaria/inmunología , Saponinas/farmacología , Vacunas Sintéticas/inmunología , Adyuvantes Inmunológicos/administración & dosificación , Animales , Células Presentadoras de Antígenos/inmunología , Citocinas/inmunología , Inflamasomas/efectos de los fármacos , Lípido A/administración & dosificación , Lípido A/farmacología , Liposomas/administración & dosificación , Ratones , Saponinas/administración & dosificación , Linfocitos T/inmunologíaRESUMEN
HZ/Su, branded as 'Shingrix', is one of the newest vaccines to be submitted for multi-national regulatory approval. It is targeted to prevent shingles, a global concern with aging populations. A live attenuated vaccine for shingles has been available for over a decade, however it is contraindicated in specific subgroups of people, and there are added concerns regarding long-term immunogenicity. HZ/Su is the first subunit vaccine developed to protect against shingles. This paper provides a critical appraisal of current evidence regarding HZ/Su.
Asunto(s)
Vacuna contra el Herpes Zóster/efectos adversos , Vacuna contra el Herpes Zóster/inmunología , Herpes Zóster/prevención & control , Herpesvirus Humano 3/inmunología , Factores de Edad , Animales , Ensayos Clínicos como Asunto , Evaluación Preclínica de Medicamentos , Herpes Zóster/complicaciones , Herpes Zóster/inmunología , Vacuna contra el Herpes Zóster/química , Humanos , Inmunidad Celular , Inmunogenicidad Vacunal , Salud Pública , Vacunación , Vacunas de Subunidad/administración & dosificación , Vacunas de Subunidad/efectos adversos , Vacunas de Subunidad/inmunologíaRESUMEN
HZ/su is an investigational recombinant subunit vaccine for the prevention of shingles, a disease resulting from the reactivation of varicella zoster virus. The vaccine is composed of recombinant varicella zoster virus glycoprotein E (gE), and liposome-based Adjuvant System AS01. To evaluate the potential local and systemic effects of this vaccine, three studies were performed in rabbits. In the first two studies, rabbits received a single intramuscular (IM; study 1) or subcutaneous (SC; study 2) dose of gE/AS01, AS01 alone (in study 2 only) or saline, and the local tolerance was evaluated up to 3 days after administration. Under these conditions, only local inflammatory reactions at the injection sites were detected by microscopic evaluation. In the third study, gE/AS01, AS01 alone or saline, were injected SC or IM on four occasions at 2 week intervals. General health status, local tolerance, ophthalmology, haematology and blood chemistry parameters were monitored. Macroscopic and microscopic evaluations were performed after termination of the study. The only treatment-related changes included a transient increase in neutrophils, C-reactive protein and fibrinogen levels and microscopic signs of inflammation at the injection sites, which are expected observations related to the elicited inflammatory reaction. The SC and IM routes of administration produced similar systemic effects. However, microscopic findings at the injection sites differed. One month after the last injection, recovery was complete in all groups. In conclusion, the single and repeated SC and IM administration of the gE/AS01 vaccine were locally and systemically well-tolerated in rabbits and support the clinical development of the vaccine. Copyright © 2016 John Wiley & Sons, Ltd.
Asunto(s)
Vacuna contra el Herpes Zóster/administración & dosificación , Vacuna contra el Herpes Zóster/efectos adversos , Herpes Zóster/prevención & control , Animales , Anticuerpos Antivirales/sangre , Evaluación Preclínica de Medicamentos , Femenino , Herpes Zóster/inmunología , Vacuna contra el Herpes Zóster/inmunología , Reacción en el Punto de Inyección/etiología , Inyecciones Intramusculares , Inyecciones Subcutáneas , Masculino , Conejos , Pruebas de Toxicidad Aguda , Pruebas de Toxicidad Subaguda , Vacunas de Subunidad/administración & dosificación , Vacunas de Subunidad/efectos adversos , Vacunas de Subunidad/inmunología , Proteínas del Envoltorio Viral/administración & dosificación , Proteínas del Envoltorio Viral/inmunologíaRESUMEN
The candidate vaccine HZ/su is being developed to prevent herpes-zoster disease (HZ). HZ occurrence is attributed to declines in varicella-zoster virus (VZV) specific T-cell immunity. HZ/su contains VZV antigen, gE, and Adjuvant System AS01B (liposome-based formulation of MPL and QS-21). In clinical trials, AS01B enhances CD4+ T-cell responses to gE. In clinical trials of other vaccines, Adjuvant Systems AS03 and AS04 also enhance antigen-specific CD4+ T-cell responses. Hence the purpose of this study was to evaluate gE formulated with AS01B, AS01E (50% less MPL and QS-21 than AS01B), AS03 or AS04 in C57BL6 mice primed with live-attenuated VZV. Four-weeks post-vaccination, the gE-specific CD4+ T-cell response to gE/AS01B was 5.4, 2.8 and 2.2-fold greater than those to gE/AS03, gE/AS04 and gE/AS03, respectively (p<0.001). Therefore in the VZV-primed mouse model, CD4+ T-cell responses to gE appeared most enhanced by AS01B, and adds further support for the use of AS01B in the HZ/su formulation.