Malaria vaccines and human immune responses

CA Long, F Zavala - Current opinion in microbiology, 2016 - Elsevier
CA Long, F Zavala
Current opinion in microbiology, 2016Elsevier
Highlights•Efficacy of RTS, S vaccine in children supports the concept of a malaria
vaccine.•RTS, S efficacy is limited and life-span is short so improvements are
necessary.•Asexual stage vaccine trials have been disappointing; TBV are in early
stages.•Antigen combinations and markers of protective immunity should be sought.•Studies
of sexual stages and vectors may provide new ways to reduce transmission.Despite
reductions in malaria episodes and deaths over the past decade, there is still significant …
Highlights
  • Efficacy of RTS, S vaccine in children supports the concept of a malaria vaccine.
  • RTS, S efficacy is limited and life-span is short so improvements are necessary.
  • Asexual stage vaccine trials have been disappointing; TBV are in early stages.
  • Antigen combinations and markers of protective immunity should be sought.
  • Studies of sexual stages and vectors may provide new ways to reduce transmission.
Despite reductions in malaria episodes and deaths over the past decade, there is still significant need for more effective tools to combat this serious global disease. The positive results with the Phase III trial of RTS, S directed to the circumsporozoite protein of Plasmodium falciparum have established that a vaccine against malaria can provide partial protection to children in endemic areas, but its limited efficacy and relatively short window of protection mandate that new generations of more efficacious vaccines must be sought. Evidence shows that anti-parasite immune responses can control infection against other stages as well, but translating these experimental findings into vaccines for blood stages has been disappointing and clinical efforts to test a transmission blocking vaccine are just beginning. Difficulties include the biological complexity of the organism with a large array of stage-specific genes many of which in the erythrocytic stages are antigenically diverse. In addition, it appears necessary to elicit high and long-lasting antibody titers, address the redundant pathways of merozoite invasion, and still seek surrogate markers of protective immunity. Most vaccine studies have focused on a single or a few antigens with an apparent functional role, but this is likely to be too restrictive, and broad, multi-antigen, multi-stage vaccines need further investigation. Finally, novel tools and biological insights involving parasite sexual stages and the mosquito vector will provide new avenues for reducing or blocking malaria transmission.
Elsevier