New adjuvants must aim to drive the immune response that is associated with lifelong protection. New adjuvants and adjuvant combinations will play many roles in future vaccines as illustrated in Figure 6.2. Adjuvants will need to be individually PD98059 cost selected

for specific vaccine targets in order to achieve the desired goal (ie enhanced immunogenicity, induction of specific immune profile etc). To deliver this aim, some adjuvants will be mixed with free antigens, while others will need to be covalently linked to the antigenic moiety as part of a complex molecule. Some examples of new adjuvants that have been evaluated in humans or that are in clinical trials are listed in Table 6.1 (also see Chapter 4 – Vaccine learn more adjuvants). Examples of new adjuvants are the nanoemulsions developed by NanoBio Corporation. Nanoemulsions are oil-in-water emulsions manufactured in various sizes ≤400 nm and stabilised by a surfactant. These technologies are amenable to topical and mucosal administration and can be used to deliver antigens or used alone to physically disrupt the outer membrane of pathogenic organisms. When administered as a vaccine, the nanoemulsion enhances vaccine antigen uptake by antigen-presenting cells, which then carry the antigen to the lymph nodes – the site of adaptive immune response initiation. Nanoemulsion

vaccines administered intranasally elicit both mucosal immunity and a systemic immune response. Modern approaches to antigen design tend to eschew classical trial and error techniques in favour of identifying the type of pathogenic structures (ie antigens) that are most likely to be important immunogens based on their structural signature

or physical location within the pathogen ( Table 6.2) (see Chapter 3 – Vaccine antigens). The T or B cell immune responses to an antigen are targeted to precise regions of the antigen (ie epitopes – either linear or three-dimensional conformational structures; in the case of protein antigens these are specific peptide epitopes). Historically, simple, linear, synthetic peptide epitope vaccines have been poorly immunogenic because they lack a specific conformation and are easily P-type ATPase degraded by a variety of extracellular and cell-surface proteases that serve to limit epitope presentation to T cells and/or result in destruction of the B-cell epitope. Peptide vaccines need to survive this environment in order to participate in successful major histocompatibility complex (MHC) class II presentation (see Chapter 2 – Vaccine immunology). Subunit and individual epitope vaccines need to be optimised to ensure adequate immunogenicity. Novel strategies are being developed and exploited in order to identify antigens recognised by T and B cells, thus facilitating a more knowledge-based vaccine design.