Obi Nnedu MD, MPH is an Infectious Disease Fellow at the University of Washington and has received a scholarship as a NIH Fogarty International Clinical Research Fellow to work in Kenya. He recently attended the MIM conference in Nairobi and shares some of his impressions here.

The 5^th Multilateral Initiative on Malaria (MIM) Pan-African conference was recently held in Nairobi. The world’s leading malaria scientists converged on the Kenyan capital to discuss strategies to eradicate malaria. Topics discussed were broad and ranged from treatment to drug resistance, from bed net use to malaria in pregnancy.  Perhaps one of the most discussed topics was malaria immunology and vaccines.

For several years, vaccines have been touted as being a great strategy for controlling and possibly eradicating malaria. Despite decades of research, an effective malaria vaccine has still not been identified.  The biggest challenge has been our lack of understanding of the correlates of immunity associated with malaria.  We are yet to understand why adults in malaria endemic areas are protected from death and severe disease associated to malaria.  At the conference there was no shortage of presentations on malaria immunology and vaccine candidates.

The most advanced malaria vaccine candidate is the RTS,S.  This vaccine was invented by Dr. Joe Cohen, vice president of Glaxo-SmithKline biologicals.  During the conference, Dr. Cohen addressed a team of journalists about the recently commenced Phase III clinical trials involving this vaccine.  16,000 children will be recruited in 7 countries namely Kenya, Tanzania, Gabon, Ghana, Burkina Faso, Malawi and Mozambique.  Dr. Cohen stressed the importance of various partners including PATH, the Bill and Melinda Gates Foundation and local in-country partners in the successful start of this vaccine trial.

The RTS,S vaccine is a combination of a malaria antigen, Circumsporozoite protein and a Hepatitis B antigen.  The proteins are combined and suspended in a liquid adjuvant system called AS01.  The combination of protein and adjuvant system, often referred to as RTS,S/AS01 will be evaluated in this Phase III trial.   RTS,S is the culmination of about 20 years of research according to Dr. Cohen.  This research started in the laboratory and is now at an advanced stage of field testing.  Dr. Cohen outlined the various steps the vaccine had undertaken to get to this current state, from phase I trials that proved the vaccine was safe to phase II trials that not only confirmed the safety of the vaccine but also showed that the vaccine had some efficacy.  In phase II trials vaccine efficacy against clinical malaria was found to be 35% to 53% and vaccine efficacy against severe malaria was 50%.  The phase III trial hopes to determine the true efficacy and safety of this vaccine by using a much larger study population.

There is great anticipation for the results of the ongoing phase III trial.  However, while the RTS,S vaccine is very promising, there are still a number of hurdles to be overcome if we are to develop a very effective vaccine.  A vaccine efficacy of around 50% as was reported in phase II trials is a step in the right direction, but a much more effective vaccine will be needed to stem the scourge of Malaria. Our inability to understand what constitutes an effective immune response to malaria means that we still don’t know how RTS,S works and what immunologic correlates can be measured to determine vaccine efficacy.  Priority areas of research include understanding malaria immunology better and identifying new malaria antigens that can be studied as vaccine candidates.  Hence, while there has been great progress, we are still years away from a truly effective malaria vaccine.