The RTS,S malaria vaccine candidate, the result of a collaboration between the Walter Reed Army Institute of Research and public-private partners, was recently recognized by Time magazine as the second most momentous medical breakthrough of 2011. Time magazine specifically cites the early results of a Phase III efficacy trial for this groundbreaking vaccine, recently published in the New England Journal of Medicine. The trial, conducted in 15,460 infants and children, at 11 study sites across Africa, demonstrated that the RTS,S vaccine was 56% effective in protecting children 5 to 17 months of age from malaria infection and was 47% effective in preventing severe cases of malaria. The final trial data, to include data pertaining to 6- to 12-week-old infants, will be available in 2014 when the trial is completed. The RTS,S Phase III field trial, which is the largest malaria vaccine trial ever conducted, represents an astounding achievement and emphasizes the global public health benefit of the U.S. Army's effort to protect the warfighter.
As a major worldwide problem, malaria affects regions of strategic importance to the United States, such as tropical Africa, Asia, Oceania, and Latin America. Approximately 300 million cases of malaria occur annually, with an estimated 1 million deaths. While infected pregnant women and children are prone to severe disease, U.S. military personnel and other individuals from non-endemic regions are also extremely susceptible to severe disease and/or death from malaria. Consequently, this high-risk medical threat has a substantial impact on operational effectiveness in deployed U.S. military forces serving in malaria-endemic areas. Malaria has been a leading cause of non-battle injury through every major U.S. conflict, including the Revolutionary War, the Civil War, World Wars I and II, the Korean Conflict, and Vietnam. Recent outbreaks have been reported among U.S. and allied troops returning from locations such as Somalia, South Korea, Liberia, French Guiana, Sierra Leone, Cote d'Ivoire, and Afghanistan. Malaria also exacts an extraordinary worldwide cost in terms of human morbidity, mortality, and economic investment.
As the most advanced malaria vaccine ever created, the RTS,S vaccine represents over two decades of collaboration between the WRAIR and key civilian partners, such as GlaxoSmithKline. The U.S. Army's role in co-development and advancement of the RTS,S vaccine has been nothing short of pivotal. The WRAIR Malaria Vaccine Development Program has executed clinical testing of over a dozen prototypes leading up to the RTS,S particle. Utilizing the WRAIR malaria challenge model, whereby humans are experimentally inoculated with malaria after vaccination, the U.S. Army conducted the first proof-of-concept clinical trial demonstrating the protective efficacy of RTS,S. U.S. Army malaria vaccine researchers also conducted the first RTS,S clinical trial in Africa. Multiple clinical trials have been executed at WRAIR to optimize vaccine presentation and safety. Critical field-site testing for the current phase III study is ongoing in Western Kenya at the U.S. Army Medical Research Unit-Kenya, an overseas laboratory of WRAIR.
Research and development of second-generation vaccine strategies has already begun. Individuals vaccinated with the current RTS,S formulation, although highly successful, would still be at risk of malaria infection and disease after prolonged exposure in malaria-endemic areas since the level of efficacy does not meet the threshold required to protect the warfighter. The second-generation malaria vaccine must achieve 80% or greater efficacy. WRAIR is continuing to develop and test improvements to the RTS,S malaria vaccine in the clinic, and it is partnering with public-private partners such as GSK, Crucell, and the PATH Malaria Vaccine Initiative for an innovative trial aimed towards achieving increased protective efficacy by "boosting" the immunogenicity of RTS,S particle after "priming" immunity with an attenuated viral platform carrying a fragment of the malaria parasite surface coat protein. The study volunteers will be malaria-naïve adults, a target population that parallels deployable U.S. military personnel.
The military malaria vaccine development effort follows a key paradigm, in that the shared goal of an optimal malaria vaccine engenders synergistic partnerships between the civilian sector and the U.S. military: the contribution of each giving genesis to a greater whole. The success of the RTS,S vaccine is a testament to this approach. As a scientific leader in the field, the U.S. military malaria vaccine community is uniquely positioned to make a critical contribution at the crossroads of force protection and global public health. Given an increasing trend in global malaria drug resistance, the staggering worldwide morbidity and mortality of malaria, and the difficulties inherent to protecting the fighting force from this threat, the development of an optimal malaria vaccine is a clear priority for the U.S. military medical research effort and our global health partners.