Risk-and-resistance models identify factors that predict psychosocial adjustment to pediatric chronic illness, including sickle cell disease (SCD), but have not been applied to understand health outcomes. The study objectives were to examine prospectively the relationship of coping and family functioning with health outcomes for adolescents with SCD, accounting for sociodemographic and psychosocial risk. Forty-one adolescents and their families (41 primary caregivers, 9 second caregivers, and 15 healthy siblings) completed paper-and-pencil measures of coping and family functioning at a baseline assessment (time 1). At both time 1 and time 2 (1 y later), disease severity, SCD complications, healthcare utilization, and average hemoglobin level were derived from medical file reviews. Time 1 disease-related parenting stress predicted time 2 health outcomes; however, there were no significant associations for coping. Families concordant in reporting lower family functioning had teens with increased disease severity and greater healthcare utilization. Examination of moderation of disease-related parenting stress by a risk index showed main effects for risk and for disease-related parenting stress for time 2 disease severity and time 2 healthcare utilization. Interaction effects were not significant. Efforts to explore specific mechanisms by which adaptive family functioning contributes to health outcomes for adolescents with SCD should continue, with particular attention to addressing the potential role of multiple sociodemographic and psychosocial risk variables.
The development of effective vaccines against neglected diseases, especially those associated with poverty and social deprivation, is urgently needed. Modern vaccine technologies and a better understanding of the immune response have provided scientists with the tools for rational and safer design of subunit vaccines. Often, however, subunit vaccines do not elicit strong immune responses, highlighting the need to incorporate better adjuvants; this step therefore becomes a key factor for vaccine development. In this review we outline some key features of modern vaccinology that are linked with the development of better adjuvants. In line with the increased desire to obtain novel adjuvants for future vaccines, the Finlay Adjuvant Platform offers a novel approach for the development of new and effective adjuvants. The Finlay Adjuvants (AFs), AFPL (proteoliposome), and AFCo (cochleate), were initially designed for parenteral and mucosal applications, and constitute potent adjuvants for the induction of Th1 responses against several antigens. This review summarizes the status of the Finlay technology in producing promising adjuvants for unsolved-vaccine diseases including mucosal approaches and therapeutic vaccines. Ideas related to adjuvant classification, adjuvant selection, and their possible influence on innate recognition via multiple toll-like receptors are also discussed.
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.
Neisseria meningitidis B proteoliposome (AFPL1 when used as adjuvant) and its derivative‐Cochleate (AFCo1) contain immunopotentiating and immunomodulating properties and delivery system capacities required for a good adjuvant. Additionally, they contain meningococcal protective antigens and permit packaging of other antigens and pathogen‐associated molecular patterns (PAMP). Consequently, we hypothesized that they would function as good vaccine adjuvants for their own antigens and also for non‐related antigens. AFPL1 is a detergent‐extracted outer membrane vesicle of N. meningitidis B transformed into AFCo1 in calcium environment. Both are produced at Finlay Institute under good manufacture practices (GMP) conditions. We show their exceptional characteristics: combining in the same structure, the potentiator activity, polarizing agents and delivery system capacities; presenting multimeric protein copies; containing multiprotein composition and multi and synergistic PAMP components; acting with incorporated or co‐administrated antigens; inducing type I IFN‐γ and IL‐12 cytokines suggesting the stimulation of human plasmocytoid precursor and conventional dendritic cells, respectively, inducing a preferential Th1 immune response with TCD4+, TCD8+, cross‐presentation and cytotoxic T‐lymphocyte (CTL) in vivo responses; and functioning by parenteral and mucosal routes. AFPL1–AFCo1 protective protein constitutions permit per se their function as a vaccine. In addition to Phase IV Men BC vaccine, AFPL1 has ended the preclinical stage in an allergy vaccine and is concluding the preclinical stage of a nasal meningococcal vaccine. In conclusion, AFPL1 and AFCo1 induced signal 1, 2 and 3 polarizing to a Th1 (including CTL) response when they acted directly as vaccines or were used as adjuvants with incorporated or co‐administered antigens by parenteral or mucosal routes. Both are very promising adjuvants.
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