It has been said that Ifakara scientists are best known by their constant desire to identify and address priority health needs of the disenfranchised. In the past 15 years, perhaps IHI’s most significant contribution in the fight against malaria has been our work on the malaria vaccine, RTS,S/ASO1. Our scientists have participated in these trials through both Phase II and Phase III studies. Today, as we begin the new year, 2017, IHI is now firmly established as a dependable site for ground-breaking developments and evaluation of high-value, life-saving products including drugs, diagnostics and vaccines, with potential to save millions of lives. in the years ahead.
In mid 2000s, we evaluated the safety and immunogenicity of an earlier version, RTS,S/AS02D in infants in Tanzania, including feasibility of incorporating this vaccine into the standard WHO Expanded Program of Immunization, in a Phase 2B trial, led by veteran clinical epidemiologist, Dr. Salim Abdulla. The conclusions of these early studies were unequivocal; that the use of RTS,S/AS02D vaccine in infants had a good safety profile, did not interfere with the other EPI vaccines and also reduced malaria infection in the infants. In later studies, in which IHI also partnered as a member of a network of 11 other African sites, the vaccine candidate prevented a substantial number of clinical malaria cases in young infants and children, when administered with and without a booster. It is now considered as having great potential for malaria control when used in combination with other effective control measures, especially in areas of high malaria transmission. The RTS, S/AOS1 is now widely accepted to provide moderate to significant protection against both clinical and severe malaria in African children, and has been very favorably evaluated by the European Medicines Agency and also by the WHO Global Malaria Advisory Policy team, which recently proposed the first pilot studies to monitor the vaccine through Phase IV studies. It is now expected that this will be the first ever malaria vaccine to be used in African children, and will initially be manufactured by GSK.
In the 2013, malaria vaccines road map, a new target was set to achieve at least one vaccine with 75% efficacy by 2030. Ahead of this curve, IHI scientists and partners had already began working on second generation malaria vaccines, relying on live sporozoites injected in humans to prevent new infections. In 2014, the institute completed the first ever controlled human malaria infections (CHMIs), where healthy adult Tanzanian were injected intradermally with aseptic, purified cryopreserved Plasmodium falciparum sporozoites (PfSPZ), the infective stage of malaria parasites.
These studies set forth a new wave of malaria vaccine studies. From the time these initial CHMIs were completed, we knew that we could expect even greater protection and possibly provide more realistic options for eventual malaria elimination. In the early CHMIs, she scientists injected healthy male volunteers with 10,000 or 25,000 sporozoites to assess whether this PfSPZ challenge was safe and/or well tolerated. In a 2014 publication, the scientists reported that nearly all the injected participants developed parasitaemia, thus they concluded these PfSPZ challenge was indeed safe, well tolerated in Tanzanian adults and also infectious.
These trials opened new ways to assess innovative vaccine candidates and also demonstrated improving capacity of institute in the fight against infectious diseases. IHI is now firmly established as a dependable site where such studies could be conducted in the future. More importantly, the work demonstrated the value of partnerships, with local and international colleagues to address specific problems effectively. Dr. Salim Abdulla, formerly the Director of IHI and arguably Africa’s most preeminent malaria vaccine trialist, has high hopes for this program of work. Having spent many years developing the program with not so much resources at hand, he believes that the role of IHI must now also include supporting other African countries to build capacity for such clinical trials. Already, IHI’s malaria vaccines work is conducted in two African countries; Tanzania and Equatorial Guinea.
Overview of work on second generation malaria vaccines at Ifakara Health Institute: This program of work is led by a clinical team at the Ifakara Health Institute Clinical Trial Facility at Kingani, Bagamoyo (IHI – CTF) which is conducting a series of studies to evaluate the potential impact of whole sporozoite malaria vaccine candidates to prevent malaria infection and thereby block transmission with the goal of achieving malaria elimination in Sub-Sahara Africa. Studies and major contributions of the work to date include:
BSPZC1 (NCT01540903): This was the first ever Controlled Human Malaria Infection (CHMI) study using purified fully infectious malaria sporozoites in an African country was conducted at IHI-CTF at Kingani, Bagamoyo in 2012. This trial demonstrated the safety and infectivity of the fully infectious purified sporozoites (PfSPZ Challenge) leading to the establishment of the CHMI model for testing new malaria vaccines and drugs in Africa
BSPZV1 (NCT02132299): Study conducted in IHI-CTF at Kingani, Bagamoyo between 2014-2015. This was the first PfSPZ Vaccine (radiation attenuated sporozoites) trial to be conducted in Africa. The trial established a very good safety and tolerability profile for the PfSPZ vaccine and was the basis for further studies in Mali and Equatorial Guinea.
BSPZV2 (NCT02613520): Study conducted in IHI-CTF at Kingani, Bagamoyo between 2015- 2016. Worldwide, this was the first PfSPZ Vaccine (radiation attenuated sporozoites) trial in adolescents and children. The trial established a very good safety and tolerability profile for PFSPZ vaccine in younger age groups and well as better immune responses in younger children. This work was the basis for further studies in Equatorial Guinea, Kenya and other African countries.