RESUMEN
Breast cancer is a worldwide health problem, and the complexity of the disease, as well as the lack of treatment specificity, generates an urgent need for developing prophylactic and therapeutic measures. Searching for novel epitope-based approaches able to induce tumour immunity, we designed virus-like particles (VLPs) derived from Human parvovirus B19 assembled of chimeric VP2 proteins displaying two epitopes from the insulin-like growth factor-1 receptor (IGF-1R). Here, we present the generation of two chimeric VP2s that retain the stability, solubility and conditions of purification and assembly of the native VP2. We generated versatile chimeric multiepitope anti-cancer vaccine candidates, which prevented and delayed tumour growth when used in a prophylactic scheme of 4 weekly immunizations prior to 4T1 cell inoculation in female BALB/c mice. The presence of specific antibodies against the displayed epitopes suggests their participation in the protective effect; in contrast, no significant proliferative T-cell responses were recorded following stimulation by specific epitopes. The results comprise an approach whereby fusing desired epitopes from cancer to the N-terminus of B19 VP2 protein can generate a library of chimeric VP2-desired epitopes for further assembly in a designed and personalized epitope delivery system.
Asunto(s)
Neoplasias de la Mama/prevención & control , Epítopos/metabolismo , Parvovirus B19 Humano/metabolismo , Receptor IGF Tipo 1/inmunología , Vacunas de Partículas Similares a Virus/administración & dosificación , Animales , Apoptosis , Neoplasias de la Mama/inmunología , Vacunas contra el Cáncer/administración & dosificación , Vacunas contra el Cáncer/inmunología , Proteínas de la Cápside/genética , Proteínas de la Cápside/metabolismo , Línea Celular Tumoral , Supervivencia Celular , Epítopos/genética , Femenino , Humanos , Inmunización , Ratones , Ratones Endogámicos BALB C , Trasplante de Neoplasias , Parvovirus B19 Humano/genética , Resultado del Tratamiento , Vacunas de Partículas Similares a Virus/genética , Vacunas de Partículas Similares a Virus/inmunologíaRESUMEN
Mucosal vaccines constitute an advantageous immunization approach to achieve broad immunization against widespread diseases; however, improvements in this field are still required to expand their exploitation. As gold nanoparticles are biocompatible and can be easily functionalized with antigens, they have been proposed as carriers for the delivery of vaccines. The study of gold nanoparticles (AuNPs) in vaccinology has been of interest for a number of research groups in recent years and important advances have been made. This review provides a summary of the AuNPs synthesis methodologies and an updated overview of the current AuNPs-based vaccines under development. The implications of these advances for the development of new mucosal vaccines as well as future prospects for the field are discussed.
Asunto(s)
Portadores de Fármacos , Oro , Nanopartículas , Vacunas/administración & dosificación , Vacunas/inmunología , Administración a través de la Mucosa , Animales , Descubrimiento de Drogas/tendencias , Humanos , Tecnología Farmacéutica/tendenciasRESUMEN
In an effort to initiate the development of a plant-based vaccination model against atherosclerosis, a cholera toxin B subunit (CTB)-based chimeric protein was designed to target both ApoB100 and CETP epitopes associated with immunotherapeutic effects in atherosclerosis. Epitopes were fused at the C-terminus of CTB to yield a protein called CTB:p210:CETPe. A synthetic gene coding for CTB:p210:CETPe was successfully transferred to tobacco plants with no phenotypic alterations. Plant-derived CTB:p210:CETPe was expressed and assembled in the pentameric form. This protein retained the target antigenic determinants, as revealed by GM1-ELISA and Western blot analyses. Higher expresser lines reached recombinant protein accumulation levels up to 10 µg/g fresh weight in leaf tissues and these lines carry a single insertion of the transgene as determined by qPCR. Moreover, when subcutaneously administered, the biomass from these CTB:p210:CETPe-producing plants was able to elicit humoral responses in mice against both ApoB100 and CETP epitopes and human serum proteins. These findings evidenced for the first time that atherosclerosis-related epitopes can be expressed in plants retaining immunogenicity, which opens a new path in the molecular farming field for the development of vaccines against atherosclerosis.
Asunto(s)
Apolipoproteína B-100/inmunología , Toxina del Cólera/genética , Toxina del Cólera/inmunología , Proteínas de Transferencia de Ésteres de Colesterol/inmunología , Nicotiana/genética , Animales , Aterosclerosis/prevención & control , Toxina del Cólera/biosíntesis , Epítopos/inmunología , Ratones , Plantas Modificadas Genéticamente/genética , Proteínas Recombinantes de Fusión/biosíntesis , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/inmunología , Vacunas/inmunologíaRESUMEN
Alternatives to pharmacological treatments for atherosclerosis are highly desirable in terms of cost and compliance. During the last two decades several vaccination strategies have been reported as an effort to develop immunotherapeutic treatments. This approach consists on eliciting immune responses able to modulate either the atherosclerosis-associated inflammatory processes or the activity of some physiological mechanisms that are up-regulated under this pathologic condition. In particular, the apolipoprotein B100 (ApoB100) and the cholesterilester transferase protein (CETP) have been targeted in these strategies. It is considered that recent progress in the development of experimental models of oral vaccines against atherosclerosis has opened a new avenue in the field: as plant-based vaccines are considered a viable platform for vaccine production and delivery at low costs, they could serve as an oral-delivered therapeutic approach for atherosclerosis in an economical and patient-friendly manner. The rationale of the design, development and evaluation of possible plant-based vaccines against atherosclerosis is discussed in this review. We identify within this approach a significant trend that will positively impact the field of atherosclerosis vaccination.