Experimental infection and protection against ... - TI Pharma

220 Chapter 11
the PfAMA1[25-545] FVO vaccine (Chapters 2, 3). Our work on AMA1 antibody
avidity illustrates that the AS02A adjuvant directs the balance of antibody
quantity and quality towards high titre antibody of lower avidity when compared
to a conventional adjuvant such as Alhydrogel (Chapter 4).
Recent advances in adjuvant research have led to the availability of many new
adjuvants [42]. With the increased understanding of host/pathogen interactions
new classes of adjuvants follow more rational design, such as Toll-like receptor
agonists or cytokines. In addition, delivery platforms have been developed to
ensure a specific presentation of the antigen to the immune system. For
example, viral platforms are designed to direct the immune response from a
classical humoral response following protein immunization to CD4+ or CD8+
responses induced by, for example, adenovirus, fowlpox or modified vaccinia
viruses [43]. Also bacterium-like particles or nanoparticles have shown to
provide benefit as carriers to potential malaria vaccines [44, 45]. Heterologous
prime-boost strategies utilizing two different adjuvants with one antigen is
another recent development that has shown to increase efficacy [46]. In
addition to adjuvants and delivery platforms, which are co-administrated with
the vaccine and designed to boost or direct the immune response, research has
focussed on the development of especially designed delivery systems, aimed at
the specific delivery of an antigen at a certain anatomical site. Nasal delivery,
needle free jet devices and intrabuccal delivery systems are examples of the
most recent developments (for example [47, 48]). Their specific advantages are
yet to be investigated.
Also AMA1 has been subjected to the addition of new adjuvants in an attempt to
increase immunogenicity [49]. Thorough adjuvant research will be required in
order to delineate the properties and optimal combination of antigen, adjuvant,
delivery platform and delivery system, a complex task requiring huge effort and
funds [42]. Direct comparisons of different adjuvants with one antigen, as we
have described (Chapter 2), will prove to be instrumental to these
developments. Unfortunately, the limited availability of newly developed
adjuvants in the public domain has restricted the number of comparative trials
so far.
In conclusion, in vitro and animal studies have raised high hopes for AMA1
vaccines, which could not be met in human efficacy trials. In addition, the phase
III clinical development of RTS,S has set high standards for the development of
any malaria vaccine, a challenge that also AMA1 has to face. The versatility of