Malaria is caused by a parasite called Plasmodium, which is transmitted via the bites of infected mosquitoes. In the human body, the parasites multiply in the liver, and then infect red blood cells. For the year 2010, WHO estimated that approximately 655 000 deaths per year were attributable to malaria (range 537,000 – 907,000), with the vast majority of these deaths occurring in sub-Saharan Africa and the majority of the remaining cases occurring in South-East Asia, the Indian subcontinent and South America. Most of the deaths in Africa are in children under the age of five years and in primigravid females. The annual number of new cases of clinical malaria episodes was estimated in 2010 to be 216 million (range 149 – 274 million).
Although immunization may make a substantial contribution, malaria control efforts are unlikely to rely primarily on vaccination in the near to mid term. Therefore it is within this context of a significant disease burden, highly concentrated on children under five years of age, and multipronged approaches to malaria disease control that evaluation of malaria vaccines will be considered.
Malaria Vaccines
Six identified species of the Plasmodium protozoan parasite can infect and cause disease in humans (P. falciparum, P. vivax, P. ovale curtisi, P. ovale wallikeri, P. malariae and P. knowlesi). P. falciparum accounts for over 90% of all malaria-attributable deaths. Vaccine development efforts to date have focused on P. falciparum and to a lesser extent on P. vivax vaccines. Over 20 P. falciparum malaria vaccine projects are currently at either advanced pre-clinical or clinical stages of evaluation. Various approaches to the development of malaria vaccines are currently under investigation. These approaches employ different production platforms and target different stages of the life-cycle of the malaria parasites.
Malaria Vaccine Standardization
Written Standards
WHO developed new guidelines on the quality, safety and efficacy of malaria vaccines targeting the pre-erythrocytic and blood stages of P. falciparum. The Expert Committee on Biological Standardization adopted the Guidelines in October 2012.
Guidelines on the quality, safety and efficacy of recombinant malaria vaccines targeting the pre-erythrocytic and blood stages of Plasmodium falciparum, Technical Report Series 980, 2012
At the time of development of these guidelines only one candidate vaccine – RTS,S/AS01, a recombinant P. falciparum malaria vaccine produced in yeast that targets the pre-erythrocytic stage – was currently under evaluation in Phase III clinical trials. The developed guidelines consist of three technical sections, namely: Part A: Guidelines on the manufacturing process and control issues relevant to recombinant antigens; Part B and Part C: Guidelines on nonclinical and clinical evaluation which may be applicable to the evaluation of other pre-erythrocytic or blood-stage P. falciparum recombinant subunit malaria vaccines.
Selected details regarding the production and testing of RTS,S/AS01 vaccine are provided as additional guidance for national regulatory authorities that may be asked to review this vaccine in the future. Comments or examples for the additional guidance are provided in small print in the Part A of the Guidelines, and appendices are also provided as examples to illustrate the current thinking/assay method at the time of guidelines adoption. Therefore, they should not be considered as final procedures, but evolving approaches.
Methodological considerations: Potency tests for recombinant adjuvanted RTS,S vaccine
The information on the methods used by the manufacturer of RTS,S/AS01 is provided separately to illustrate the nature of the manufacturing and testing procedures. These methods are subject to further development and the information on that matter will be periodically updated.
Methodological considerations: Potency tests for recombinant adjuvanted RTS,S vaccine
