Study reveals why malaria vaccine only partially protected children, infants
- Date:
- October 22, 2015
- Source:
- NIH/National Institute of Allergy and Infectious Diseases
- Summary:
- Using new, highly sensitive genomic sequencing technology, an international team of researchers has found new biological evidence to help explain why the malaria vaccine candidate RTS,S/AS01 (called RTS,S) provided only moderate protection among vaccinated children during clinical testing. The researchers found that genetic variability in the surface protein targeted by the RTS,S vaccine likely played a significant role.
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Using new, highly sensitive genomic sequencing technology, an international team of researchers has found new biological evidence to help explain why the malaria vaccine candidate RTS,S/AS01 (called RTS,S) provided only moderate protection among vaccinated children during clinical testing. The researchers, funded in part by the National Institute of Allergy and Infectious Diseases at the National Institutes of Health, found that genetic variability in the surface protein targeted by the RTS,S vaccine likely played a significant role. The findings are published online today in the New England Journal of Medicine.
The RTS,S vaccine was designed to target the circumsporozoite (CS) protein found on the surface of malaria-causing Plasmodium parasites. However, while the CS protein is genetically diverse, meaning that it has different variants, the RTS,S vaccine incorporates only one variant. In an evaluation of blood samples from nearly 5,000 of the infants and children who participated in Phase 3 clinical testing of the vaccine, the researchers found that the RTS,S vaccine was most effective at preventing malaria in children ages 5 to 17 months infected with parasites with the same protein variant as the RTS,S vaccine, while a mismatch corresponded with a lesser degree of protection. This differential effect was not seen in blood samples from vaccinated infants ages 6 to 12 weeks.
Previous studies that have looked at the genetic variations in the CS protein did not suggest that these variations may limit or restrict vaccine protection. This new study included a larger sample size and used advanced, more sensitive genomic sequencing technology than previously available. The findings will inform future malaria vaccine development, and the genomics approach used could be applied to other infectious diseases with changing vaccine targets, according to the authors.
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Materials provided by NIH/National Institute of Allergy and Infectious Diseases. Note: Content may be edited for style and length.
Journal Reference:
- Daniel E. Neafsey, Michal Juraska, Trevor Bedford, David Benkeser, Clarissa Valim, Allison Griggs, Marc Lievens, Salim Abdulla, Samuel Adjei, Tsiri Agbenyega, Selidji T. Agnandji, Pedro Aide, Scott Anderson, Daniel Ansong, John J. Aponte, Kwaku Poku Asante, Philip Bejon, Ashley J. Birkett, Myriam Bruls, Kristen M. Connolly, Umberto D’Alessandro, Carlota Dobaño, Samwel Gesase, Brian Greenwood, Jonna Grimsby, Halidou Tinto, Mary J. Hamel, Irving Hoffman, Portia Kamthunzi, Simon Kariuki, Peter G. Kremsner, Amanda Leach, Bertrand Lell, Niall J. Lennon, John Lusingu, Kevin Marsh, Francis Martinson, Jackson T. Molel, Eli L. Moss, Patricia Njuguna, Christian F. Ockenhouse, Bernhards Ragama Ogutu, Walter Otieno, Lucas Otieno, Kephas Otieno, Seth Owusu-Agyei, Daniel J. Park, Karell Pellé, Dana Robbins, Carsten Russ, Elizabeth M. Ryan, Jahit Sacarlal, Brian Sogoloff, Hermann Sorgho, Marcel Tanner, Thor Theander, Innocent Valea, Sarah K. Volkman, Qing Yu, Didier Lapierre, Bruce W. Birren, Peter B. Gilbert, Dyann F. Wirth. Genetic Diversity and Protective Efficacy of the RTS,S/AS01 Malaria Vaccine. New England Journal of Medicine, 2015; 151021140107004 DOI: 10.1056/NEJMoa1505819
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