Human prophylactic vaccine adjuvants and their determinant role in new vaccine formulations

Adjuvants have been considered for a long time to be an accessory and empirical component of vaccine formulations. However, accumulating evidence of their crucial role in initiating and directing the immune response has increased our awareness of the importance of adjuvant research in the past decade. Nevertheless, the importance of adjuvants still is not fully realized by many researchers working in the vaccine field, who are involved mostly in the search for better target antigens. The choice of a proper adjuvant can be determinant for obtaining the best results for a given vaccine candidate, but it is restricted due to intellectual property and know-how issues. Consequently, in most cases the selected adjuvant continues to be the aluminum salt, which has a record of safety, but predominantly constitutes a delivery system (DS). Ideally, new strategies should combine immune potentiators (IP) and DS by mixing both compounds or by obtaining structures that contain both IP and DS. In addition, the term immune polarizer has been introduced as an essential concept in the vaccine design strategies. Here, we review the theme, with emphasis on the discussion of the few licensed new adjuvants, the need for safe mucosal adjuvants and the adjuvant/immunopotentiating activity of conjugation. A summary of toxicology and regulatory issues will also be discussed, and the Finlay Adjuvant Platform is briefly summarized.

Respuesta inmune sistémica y mucosal contra Neisseria meningitidis B inducida por estrategia de vacunación simultànea mucosal y parental

Immunization is one of the most successful and cost-effective health interventions ever. Immunization have been helping to reduce child mortality, improving maternal health and combating infectious diseases. In spite of its, undisputed past success and promising future, however, immunization remains an unfinished agenda because of them inadequate coverage. Several factors have been largely responsible of a difficulty to attain immunization coverage and have been recognized as a problems of current vaccines, such as: the number of dose, excessive use of parenteral route, a small number of adjuvants approve for use in human, higher reactogenicity and unavailability against intracellular pathogens, infected or altered cells and scanty feasibility to combined more than one antigen in the same formulation. For bacterial meningitis WHO estimates that 1,2 million cases occur annually and Neisseria meningitidis is the etiological agent in more than 40 percent of these cases although some meningococcal vaccines are available. To bear in mind these principals problems, a novel protocol for vaccination against N meningitidis called Single Time Vaccination Strategy (SinTimVaS) is proposed. Using female BALB/c mice, we induce systemic and mucosal immune responses against N meningitidis with only one parenteral and one mucosal dose at the same time, employing the Finlay Adjuvants derivate from N meningitidis, AFPL1 and AFCo1, respectively. In conclusion, SinTimVaS could increase the vaccination coverage and reduce the time-cost of vaccine campaigns, adding the possibility to increase the herd immunity by mucosal specific response induction(AU)

Enfoques mucosales en vacunologia de Neisseria

Meningococcal B strains accounts for some 72 percent and 28 percent of meningococcal diseases in infants and toddlers in Europe and the USA, respectively. Nevertheless, meningococcal diseases are rare in Cuba owing to the wide spread program on antimeningococcal vaccination in the country. Finlay Institute is one of the pioneering organizations in Neisseria Vaccinology mainly by its contribution to N. meningitidis serogroup B outer membrane-based bivalent vaccine, VA-MENGOC-BC™. This vaccine was given intramuscularly in more than 60 million doses corresponding 10,7 millions of them to Cuban young adults, children, and infants. However, most dangerous or commensally Neisseria strains enter and establish in the mucosa, where the secretory (S) IgA is the main specific guardian and is mainly induced by mucosal routes. However, few mucosal vaccines exist principally due to the absent of mucosal adjuvants. We develop a Finlay Adjuvant (AF) platform based in outer membrane vesicles (Proteoliposome, PL) and its derivate Cochleate (Co). AFPL1 derived from serogroup B N meningitidis is a potent Th1/CTL driving parenteral adjuvant. AFCo1 is a potent mucosal adjuvant. Therefore, we sought to go deeper in the possible mucosal cross recognition between N. meningitidis serogroups and Neisseria species and explore a concurrent mucosal and parenteral immunization strategy (SinTimVaS) in order to develop suitable mucosal vaccines. Experiments were conducted in Balb/c or C57Bl6 mice with mucosal and systemic immunization using AFCo1 and AFPL1. Human sera and saliva were also analyzed for cross cognition. Mucosal cross recognition at SIgA level in human saliva between N. meningitidis serogroups B, A, C, Y, and W135 were observed. This SIgA cross recognition response was also observed between pathogenic (N meningitidis serogroup B, N gonorrhoeae) and non-pathogenic strains (N flava, N lactamica). The possible influence of meningococcal vaccination ...(AU)

Recidiva local y afectación metastásica única de tumor renal. Factores pronósticos y supervivencia / Local relapse and single site of metastatic involvement of renal tumour. Prognostic factors and survival

Objetivo: Valorar las características clínicas y patológicas y la supervivencia de los tumores renales que presentaron recidiva local o metástasis única y fueron tratadas quirúrgicamente. Material y método: Estudio retrospectivo de 321 nefrectomías valorando las variables clínicas y patológicas de aquellos pacientes que presentaron recidiva local o metástasis única y fueron tratados quirúrgicamente. Estudio y comparación de la supervivencia en los diferentes grupos. Resultados: El único factor influyente de forma independiente en la presentación de recidivalocal es el estadio patológico. La recidiva local y la presencia de metástasis única tienen una supervivencia similar, estadísticamente peor que el resto de pacientes no metastásicos al diagnóstico, pero mejor que los pacientes con presencia de metástasis al diagnóstico. Conclusiones: La presencia de recidiva local tiene el mismo pronóstico que la progresión en forma de una única metástasis resecable, pero mejor pronóstico que los pacientes inicialmente metastásicos a los que se realiza nefrectomía previa al tratamiento sistémico (AU)

Objective: To evaluate the clinical and pathological characteristics and survival in patients surgically treated for renal tumours that had local recurrence or metastasis to a single site. Material and Methods: A retrospective study of 321 nephrectomies, evaluating the clinical and pathological variables in patients having local recurrence or metastasis to a single site, and who were treated surgically. Study and comparison of survival in the different groups. Results: The only factor found to have an independent influence on local recurrence is pathological stage. Local recurrence and the presence of metastasis to a single site have similar survival rates, both being statistically worse than in patients without metastasis at diagnosis, but better than in those having metastasis at diagnosis. Conclusions: The presence of local recurrence has the same prognosis as a single excisable metastatic site, the prognosis being better than those initially with metastasis subjected to nephrectomy before receiving systemic treatment (AU)

Feocromocitoma con trombo en cava / Pheochromocytoma with thrombus in cava

El feocromocitoma, paraganglioma de localización suprarrenal, es un tumor cromafín secretor de catecolaminas. La extensión de éstos tumores a vena cava es rara y que el trombo alcance la aurícula derecha es excepcional. Presentamos el caso de una paciente que, sin clínica previa, presentó un cuadro de disfunción multiorgánica como primera manifestación de un tumor suprarrenal con extensión vascular hasta la aurícula derecha y afectación de la vena suprahepática derecha (AU)

Pheochromocytoma, a paraganglioma of suprarenal location, is a catecholamine-secreting chromaffin cell tumour. Spread of these tumours to the vena cava is rare and the thrombus only reaches the right atrium in exceptional cases. We present the case of a patient who, without previous symptomatology, presented with a clinical picture of multiorganic dysfunction with primary manifestation of a suprarenal tumour with vascular spread to the right atrium affecting the right suprahepatic vein (AU)

Utilidad del pet en el diagnóstico y respuesta al tratamiento en un tumor germinal extragonadal de presentación atípica / Pet utility in the diagnostic and follow up in atipic presentation of extragonadal germ cell tumour

Los tumores primarios de origen extragonadal son raros, con menos de 1.000 casos descritos en la literatura. Aunque la incidencia de los TGE (tumores germinales extragonadales) es desconocida, datos clínicos sugieren que constituyen alrededor del 3-5 por ciento de todos los tumores de células germinales. Presentamos un caso clínico de TGE con una presentación clínica atípica. Exponemos nuestra experiencia diagnóstica y terapéutica en este tipo de lesiones (AU)

Primary tumors of extragonadal origin are rare, with fewer than 1000 cases described in the literature. Although the exact incidence of EGTs is unknown, clinical data suggest that roughly 3% to 5% of all germ cell tumors. We expouse a case report of EGT with unusually clinic presentation. We present our diagnostic and terapeutic experience in this injuries (AU)