SWISS MEDICAL WEEKLY : VACCINE ADJUVANTS

Vaccine adjuvants Aluminium was the first commercial vaccine adjuvant, used to improve the immunogenicity of diphtheria vaccine. Until recently, oil-in-water emulsions were the only other compounds added to the list of adjuvants. In recent years, many potential new classes of adjuvants have been discovered and have undergone testing for efficacy and safety in humans. This review discusses the different mechanisms of action of the available adjuvants and appraises new approaches using “vaccine-omics” to discover novel types of adjuvants. Abstract The purpose of vaccination is to prime a naïve immune system and establish a pathogen-specific protective immunological memory. Essentially, vaccination induces two important immune phenotypes: (i.) a virus-specific B-cell response with production of neutralising anti­bodies with the help of a T helper cell type 2 (Th2) memory and/or (ii.) a virus-specific cytotoxic T cell and T helper cell type 1 (Th1) memory. Currently, most commercially available vaccines target the induction of neutralising antibodies. The vaccine-induced immune response is influenced by: (i.) vaccine factors, i.e., type and composition of the antigen(s), (ii.) host factors i.e., genetic differences in immune-signalling or senescence, and (iii.) external factors such as immunosuppressive drugs or diseases. Adjuvanted vaccines ­offer the potential to compensate for a lack of stimulation and improve pathogen-specific protection. A large amount of data regarding adjuvanted vaccines concerns their safety and tolerability. Prevention of ­infection compared with nonadjuvanted vaccines is rarely examined. The best immune biomarker indicative of protection and prevention of infection is debated: most research has considered antibody titres, which are easy to measure, but T-cell responses, especially Th2 ­cytokine release and measurement B-cell activation directly might correlate better with protection. The adjuvant potential of aluminium salts was discovered in 1926, but their mechanism of action is complex and still not fully understood. In the last decade, new data on their mechanism of action have emerged, but most studies on vaccine efficacy have been performed in mice. MF59 and AS03 are squalene-based oil-in-water emulsions. Experiments with nanoparticle adjuvants suggest that the particle size may be a key factor for their activity: microspheres with diameters of <10 nm seem to ­activate antigen presenting cells, whereas particles with diameters of 30–100 nm show a slow release of antigen. MF59 has a droplet size of approximately 130 nm. ­Although the immunogenicity of MF59- and AS03-adjuvanted vaccines has been demonstrated in terms of antibody responses, the increased protective effect has only been shown in two studies and one study, respectively. New small molecules may help to significantly increase vaccine responses. Emerging technology such as in-­silico modelling of adjuvant receptor interactions using super-computers; combined with RNA sequencing and microarray single nucleotide polymorphisma discovery, uncovering critical steps in vaccine responses, will bring about the design of novel classes of adjuvants. Read the article This is a summary of a paper that was published on www.smw.ch. Must be cited as: Egli A, Santer D, Barakat K, Zand M, Levin A, Vollmer M, Weisser M, Khanna N, Kumar D, Tyrrell L, Houghton M, Battegay M, O’Shea D. Vaccine adjuvants – understanding molecular mechanisms to improve vaccines. Swiss Med Wkly. 2014;144:w13940.

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