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

Abstract

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 lactamicaantigens complexed with a novel cationic adjuvant

“…27 Aluminum compounds, which were identified as having immunostimulatory properties more than 70 y ago, remain the only adjuvant that is licensed worldwide. 28 However, this adjuvant exhibits low colloid stability. 23 In the present work, cationic nanoparticles formed by DDA-BF and N. lactamica OMV (OMV-DDA-BF) were tested as an immunogen against N. meningitidis for the first time.…”

Post-operative unadjuvanted therapeutic xenovaccination with chicken whole embryo vaccine suppresses distant micrometastases and prolongs survival in a murine Lewis lung carcinoma model

“…Various preventive and therapeutic vaccines are generally used with vaccine adjuvants that shape and potentiate the induced immune responses, thereby increasing the efficacy of vaccination (45,46). In a previously investigated metastatic LLC model, where B. subtilis was used as an adjuvant for an autologous tumour lysate-based vaccine, it failed to demonstrate satisfactory clinical benefits (39); an underperformance repeated in the present study.…”

“…In addition, distinct spectrum of TAAs in B16 melanoma and LCC lung cancer cells may be responsible for the xeno rat vaccine exhibiting (39), and this underperformance was repeated in the present study. Various vaccines (preventive and therapeutic) are generally used with vaccine adjuvants that shape and potentiate the induced immune responses, thereby increasing the efficacy of vaccination (45,46). The present study, however, demonstrates that a unadjuvanted xenogeneic vaccine (xeno chicken) can be successfully applied, and the xenogeneic component of the vaccine can serve as sufficient adjuvant on in its own right.…”

Mucosal and systemic immune responses induced by a single time vaccination strategy in mice

“…p values of <0.001, <0.01, and <0.05 are considered statistically significant and are represented by the letters a, b, and c, respectively, above the bars. tiating effect through MyD88-dependent and MyD88-independent TIR-domain-containing adaptor-inducing interferon-␤ based pathways (Pérez et al 2012).…”