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SUMMARY:Blood-stage malaria vaccine development: the impact of vaccine pla
 tform and timing of booster dosing - Dr Carolyn Nielsen\; University of Ox
 ford
DTSTART:20221020T130000Z
DTEND:20221020T140000Z
UID:TALK176498@talks.cam.ac.uk
CONTACT:Bobbie Claxton
DESCRIPTION:The development of a highly effective vaccine remains a key st
 rategic goal to aid the control and eventual eradication of Plasmodium fal
 ciparum malaria. In recent years\, the reticulocyte-binding protein homolo
 g 5 (RH5) has emerged as the most promising blood-stage P. falciparum cand
 idate antigen to date\, capable of conferring protection against stringent
  challenge in Aotus monkeys. We first reported on a dose-escalation phase 
 Ia study in healthy\, malaria-naive adult volunteers using established vir
 al vectors\, the replication-deficient chimpanzee adenovirus serotype 63 (
 ChAd63)\, and the attenuated orthopoxvirus modified vaccinia virus Ankara 
 (MVA). Vaccine-induced anti-RH5 serum antibodies exhibited cross-strain fu
 nctional growth inhibition activity (GIA) in vitro\, targeted linear and c
 onformational epitopes within RH5\, and inhibited key interactions within 
 the RH5 invasion complex. Next\, we undertook a phase I/IIa clinical trial
  of the RH5.1 recombinant protein vaccine\, formulated in AS01B adjuvant. 
 We show that GIA strongly correlates with in vivo reduction of the parasit
 e growth rate in a controlled human blood-stage malaria infection model\, 
 establishing a crucial correlate of protection for blood-stage malaria vac
 cine development. We also demonstrate that the protein/AS01B platform indu
 ces a higher-magnitude antigen-specific circulating Tfh cell response and 
 that this correlates with peak anti-PfRH5 IgG concentrations (10-fold high
 er in protein/AS01B versus viral vector vaccinees)\, frequency of PfRH5-sp
 ecific memory B cells\, and antibody functionality. Also notable in the pr
 otein/AS01B trial is that a booster dosing regimen using a delayed and fra
 ctional third dose (DFx)\, in contrast to three doses given at monthly int
 ervals\, led to significantly improved serum antibody longevity over ∼2 
 years of follow-up. Subsequent analyses of RH5-specific B cells revealed e
 nriched plasma cell and Ig / protein export signals in the monthly dosing 
 group as compared to DFx vaccinees. Taken together\, our data provide a fr
 amework to guide rational design and delivery of next-generation vaccines 
 to protect against malaria disease.\n\nDr Carolyn Nielsen is a Senior Immu
 nologist working with Prof Simon Draper’s Blood-Stage Malaria Group in t
 he Department of Biochemistry (previously based at the Jenner Institute)\,
  University of Oxford. The focus of her current work and recent Sir Henry 
 Wellcome Postdoctoral Fellowship is on the impact of vaccine platform and 
 booster dosing regimen on the cellular drivers of humoral immunity. Dr Nie
 lsen is particularly interested in cytometry\, sequencing\, and systems ap
 proaches to understand heterogeneity in B cell immunogenicity. Prior to he
 r postdoctoral work in Oxford\, Dr Nielsen completed her PhD with Prof Ele
 anor Riley at the London School of Hygiene and Tropical Medicine.\n\n\n\n\
 n\n\nClick here to join live - https://us06web.zoom.us/j/89285037013 
LOCATION:Online via zoom &amp\; Kings Hedges Room 
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