R21 malaria vaccine is protective against intradermal but not intravenousPlasmodium falciparumsporozoites in a randomized controlled human malaria infection study in Kenyan adults
Author:
Kapulu Melissa CORCID, Orenge Francesca, Kimani Domtila, Kibwana Elizabeth, Kibet Hillary, Mutahi Mary, Datoo Mehreen S, Bellamy Duncan, Musembi Janet, Ngoto Omar, Rashid Hamisi, Akinyi Stellamaris, Mwatasa Mwaganyuma H, Nyamako Lydia, Keter Kelvias, Gatheru Rose, Mutiso Agnes, Musyoki Jennifer, Mwacharo Jedidah, Abebe Yonas, James Eric J, Billingsley Peter F, Ngetsa Caroline, Mosobo Moses, Makale Johnstone, Tawa Brian, Wamae Kevin, Ochola-Oyier Lynette I, Wambua Juliana, Lawrie Alison, Ramos-Lopez Fernando, Roberts Rachel, Richie Thomas L, Sim B. Kim Lee, Hoffman Stephen L, Ewer Katie J, Hill Adrian V S, Hamaluba Mainga, Bejon Philip
Abstract
AbstractFalciparum malaria is a substantial public health problem. Vaccines and monoclonal antibodies targeting thePlasmodium falciparum(Pf) circumsporozoite protein (CSP) are promising control strategies. The protective mechanisms of anti-PfCSP antibodies are incompletely understood, and levels of anti-PfCSP antibodies are inconsistently predictive of protection. We undertook controlled human malaria infections in volunteers vaccinated with the PfCSP-based vaccine R21/Matrix-M, using either intradermal injection (ID) or direct venous inoculation (DVI) ofP. falciparumsporozoites (PfSPZ Challenge). R21/Matrix-M was highly protective against intradermal inoculation of PfSPZ Challenge (i.e. 100%, 12 out of 12) but not protective against PfSPZ Challenge by DVI (i.e. 0%, 0 out of 5). These findings imply that the variable delivery of Pf sporozoites into capillaries rather than the subdermal layers by infectious mosquito bites can account for the inconsistent protection provided by anti-PfCSP antibodies.
Publisher
Cold Spring Harbor Laboratory
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