Experimental infection and protection against ... - TI Pharma

232 Chapter 11
immunoglobulins has never been tried in malaria research. Such experiments
are difficult to perform nowadays because of increased safety requirements
associated with the transfer of blood products. Once proof of principle for AMA1
is established, diversity covering [20, 21] or combination vaccines with the blood
stage antigen MSP1 [135, 136], Circumsporozoite protein [137, 138] or a mix of
more than two antigens [139], have better chances for success and the search
for effective adjuvants, delivery platforms and delivery systems can be guided by
a comparison of antibody responses.
The inoculation of whole sporozoites is a very potent and efficient way of
inducing protection against Pf malaria. However, the translation of this approach
into a whole sporozoite vaccine faces several safety issues. In order to ensure
safety the development of an in vitro sporozoite potency test will be of vital
importance. Recent results with multiply-attenuated parasite lines leading to
blood-infection, are a signal to scientists to take a prudent approach before
administering live vaccine products to large populations.
In conclusion, immunological research elucidating mechanisms of protection and
enhancing efficacy through antigen-adjuvant combinations may be warranted
for the subunit AMA1 vaccine candidate, whereas the promising efficacy results
of the CPS immunisation strategy might stimulate a more pragmatic approach to
develop an implementable whole-organism based vaccine. This thesis shows
that clinical infection trials in small numbers of healthy human volunteers,
although subject to rigorous ethical procedures, can provide valuable insight for
the development of any type of malaria vaccine that would not have been
acquired otherwise. Such tools may prove to be essential to meet the ambitious
goals of the Malaria Vaccine Technology Roadmap by 2015–2025.