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CID EPISODE 1274 TRIAL

A significant difference in ADRB activity was seen between KCS volunteers with minimal and definite prior exposure to malaria and significant increases were seen in ADRB activity post-CHMI in Kenyan volunteers. Serum from volunteer 110 in KCS, who demonstrated a dramatically reduced PMR in vivo, had no in vitro GIA prior to CHMI but the highest level of ADRB activity. Antibodies to AMA1 and schizont extract correlated with parasite multiplication rate (PMR) post-CHMI in KCS. Results:Clear serological differences were observed pre- and post-CHMI by ELISA between malaria-naïve UK volunteers in VAC049, and Kenyan volunteers who had prior malaria exposure. We assessed antibody responses to three key blood-stage merozoite antigens and functional activity using two candidate measures of anti-merozoite immunity the growth inhibition activity (GIA) assay and the antibody-dependent respiratory burst activity (ADRB) assay.

Methods: We describe detailed serological and functional immunological responses pre- and post-CHMI for participants in the KCS and compare these with those from malaria-naïve UK volunteers who also underwent CHMI (VAC049) ( NCT01465048) using PfSPZ Challenge. This study used aseptic, cryopreserved, attenuated Plasmodium falciparum sporozoites administered by needle and syringe (PfSPZ Challenge) and was the first to evaluate parasite dynamics post-CHMI in individuals with varying degrees of prior exposure to malaria.

CID EPISODE 1274 TRIAL

The first Kenyan Challenge Study (KCS) (Pan African Clinical Trial Registry: PACTR20121100033272) was performed in 2013 with the aim of establishing the CHMI model in Kenya.

8Department of Tropical Medicine, University of Oxford, Oxford, UKīackground: The timing of infection is closely determined in controlled human malaria infection (CHMI) studies, and as such they provide a unique opportunity to dissect changes in immunological responses before and after a single infection.

6Division of Clinical Pharmacology, Hôpital Beaumont, Université de Lausanne, Lausanne, Switzerland.

5Centre for Research in Therapeutic Sciences, Strathmore University, Nairobi, Kenya.

4Centre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya.

3Centre for Geographical Medical Research (Coast), Kenya Medical Research Institute-Wellcome Trust, Kilifi, Kenya.

2Laboratory of Malaria and Vector Research, NIH-National Institute of Allergy and Infectious Diseases, Rockville, MD, USA.

1The Jenner Institute, University of Oxford, Oxford, UK.

Hoffman 7, Bernhards Ogutu 4,5, Adrian V. Longley 1 †, Thomas Mercier 6, Laurent Decosterd 6, Carole A. Juma 4,5, Charles Magiri 4, Alfred Muia 4, Jing Jin 1, Alexandra J. Elias 1, Kazutoyo Miura 2, Gathoni Kamuyu 3, Elizabeth A.