Adjuvants: Classification,Modus Operandi, and Licensing

Abstract

Vaccination is one of the most efficient strategies for the prevention of infectious diseases. Although safer, subunit vaccines are poorly immunogenic and for this reason the use of adjuvants is strongly recommended. Since their discovery in the beginning of the 20th century, adjuvants have been used to improve immune responses that ultimately lead to protection against disease. The choice of the adjuvant is of utmost importance as it can stimulate protective immunity. Their mechanisms of action have now been revealed. Our increasing understanding of the immune system, and of correlates of protection, is helping in the development of new vaccine formulations for global infections. Nevertheless, few adjuvants are licensed for human vaccines and several formulations are now being evaluated in clinical trials. In this review, we briefly describe the most well known adjuvants used in experimental and clinical settings based on their main mechanisms of action and also highlight the requirements for licensing new vaccine formulations.

A self-aggregating peptide: implications for the development of thermostable vaccine candidates

“…5d). To further confirm that the vaccination with PH (1-110) GFP particles induce also cellular immunity, we conducted a cell proliferation experiment (see the Additional file 6) comparing the PH (1-110) GFP particles against Freund's adjuvant that generates a strong cellular response [31]. As illustrated in the figure, the PH (1-110) GFP particles induced a moderate cellular proliferation, characteristic of cellular immunity.…”

“…F5506) were used. We decided to use the CFA and IFA in this experiment because, unlike Alum, broader stimulation of the cellular response has been previously observed [31,42]. Blood samples were taken for 6 weeks at 14-day intervals (Additional file 6A).…”

Old and new adjuvants

“…Muramyl dipeptide expressed by MTb in CFA activates NOD2 receptors [67,68]. Incomplete Freund’s adjuvant (IFA) composed of just the mineral oil component of CFA, was used in influenza vaccines in the 1950s to enhance antibody responses [69], and due to significant side effects [70] has only been studied in clinical trials of HIV and some cancer vaccines [71]. It enhances accumulation of APCs, antigen uptake and cytokine production and a non-polarized TH1/TH2 response with enhanced IgG1/IgG2a antibody responses [72–76].…”

Total Leishmania antigens with Poly(I:C) induce Th1 protective response

“…Natural and synthetic double‐stranded RNA (dsRNA), such as the synthetic Poly(I:C) adjuvant, act as toll‐like receptor 3 agonist and induce the production of type I interferons (IFN) and other cytokines . Poly(I:C) and other synthetic derivatives have been evaluated in animal and human clinical trials, demonstrating good efficacy and safety profiles …”