TLR9 and endogenous adjuvants of the whole blood-stage malaria vaccine

Abstract

Vaccination has been a successful tool in the protection against many infectious diseases, and recent advances in biotechnology have created new techniques and strategies to produce safe and efficacious vaccines for human use. However, developing a protective vaccine against malaria has been a challenge. In this article, we focus on an old approach with some new modifications, the so-called whole-parasite vaccination strategy against blood-stage Plasmodium falciparum, the deadliest human malarial agent. In addition, we discuss recent developments in our understanding of how the endogenous adjuvant activity in the parasites, which functions via Toll-like receptor 9, acts as a double-edged sword between protective vaccination and pathological responses against malaria infection.

Keywords::

• adaptive immunity
• adjuvant
• hemozoin
• innate immunity
• malaria
• TLR9

Acknowledgements

The authors thank members of the Akira Laboratory and the Horii Laboratory for discussions and valuable comments and R Culleton for critical reading of the manuscript.

Financial & competing interests disclosures

Cevayir Coban, Toshihiro Horii, Shizuo Akira and Ken J Ishii were supported by Japan Science and Technology as well as by grants from the Ministry of Education, Culture, Sports, Science and Technology in Japan, the RT Fund for Technology Development and Core Research for Evolutional Science and Technology (CREST). Cevayir Coban is also supported by the Bill and Melinda Gates Foundation (round 1 recipient of the Grand Challenges and Explorations grant) and the Osaka University Career Design Laboratory for Women. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.