In 2013 there were an estimated 584,000 deaths and 198 million clinical illnesses
due to malaria, the majority in sub-Saharan Africa. Vaccines would be the ideal addition
to the existing armamentarium of anti-malaria tools. However, malaria is caused by
parasites, and parasites are much more complex in terms of their biology than the
viruses and bacteria for which we have vaccines, passing through multiple stages of
development in the human host, each stage expressing hundreds of unique antigens.
This complexity makes it more difficult to develop a vaccine for parasites than for
viruses and bacteria, since an immune response targeting one stage may not offer protection
against a later stage, because different antigens are the targets of protective immunity
at different stages. Furthermore, depending on the life cycle stage and whether the
parasite is extra- or intra-cellular, antibody and/or cellular immune responses provide
protection. It is thus not surprising that there is no vaccine on the market for prevention
of malaria, or any human parasitic infection. In fact, no vaccine for any disease
with this breadth of targets and immune responses exists. In this limited review,
we focus on four approaches to malaria vaccines, (1) a recombinant protein with adjuvant
vaccine aimed at Plasmodium falciparum (Pf) pre-erythrocytic stages of the parasite cycle (RTS,S/AS01), (2) whole sporozoite
vaccines aimed at Pf pre-erythrocytic stages (PfSPZ Vaccine and PfSPZ-CVac), (3) prime
boost vaccines that include recombinant DNA, viruses and bacteria, and protein with
adjuvant aimed primarily at Pf pre-erythrocytic, but also asexual erythrocytic stages,
and (4) recombinant protein with adjuvant vaccines aimed at Pf and Plasmodium vivax sexual erythrocytic and mosquito stages. We recognize that we are not covering all
approaches to malaria vaccine development, or most of the critically important work
on development of vaccines against P. vivax, the second most important cause of malaria. Progress during the last few years has
been significant, and a first generation malaria candidate vaccine, RTS,S/AS01, is
under review by the European Medicines Agency (EMA) for its quality, safety and efficacy
under article 58, which allows the EMA to give a scientific opinion about products
intended exclusively for markets outside of the European Union. However, much work
is in progress to optimize malaria vaccines in regard to magnitude and durability
of protective efficacy and the financing and practicality of delivery. Thus, we are
hopeful that anti-malaria vaccines will soon be important tools in the battle against
malaria.
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