scholarly journals Transcriptome profiling reveals functional variation in Plasmodium falciparum parasites from controlled human malaria infection studies

EBioMedicine ◽  
2019 ◽  
Vol 48 ◽  
pp. 442-452 ◽  
Author(s):  
Regina Hoo ◽  
Ellen Bruske ◽  
Sandra Dimonte ◽  
Lei Zhu ◽  
Benjamin Mordmüller ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Infection ◽  
Transcriptome Profiling ◽  
Functional Variation ◽  
Human Malaria ◽  
Controlled Human Malaria Infection

scholarly journals Multidose Priming and Delayed Boosting Improve PfSPZ Vaccine Efficacy against Heterologous P. falciparum Controlled Human Malaria Infection

2020 ◽  
Author(s):  
Kirsten E Lyke ◽  
Alexandra Singer ◽  
Andrea A Berry ◽  
Sharina Reyes ◽  
Sumana Chakravarty ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Vaccine Efficacy ◽  
Malaria Infection ◽  
Human Malaria ◽  
Group 4 ◽  
Controlled Human Malaria Infection ◽  
Group 3 ◽  
Group 2 ◽  
The Impact ◽  
Group 1

Abstract Background A live-attenuated Plasmodium falciparum (Pf) sporozoite (SPZ) vaccine (PfSPZ Vaccine) has shown up to 100% protection against controlled human malaria infection (CHMI) using homologous parasites (same Pf strain as in the vaccine). Using a more stringent CHMI, with heterologous parasites (different Pf strain), we assessed the impact of higher PfSPZ doses, a novel multi-dose prime regimen, and a delayed vaccine boost upon vaccine efficacy. Methods Four groups of 15 healthy, malaria-naïve adults were immunized. Group (Grp) 1 received five doses of 4.5x10 5 PfSPZ (days 1, 3, 5, 7; week 16). Grps 2, 3 and 4 received three doses (weeks 0, 8, 16) with Gp 2 receiving 9.0×10 5/dose, Grp 3 receiving 18.0×10 5/dose, and Grp 4 receiving 27.0×10 5 for dose 1 and 9.0×10 5 for doses 2 and 3. VE was assessed by heterologous CHMI after 12 or 24 weeks. Volunteers not protected at 12 weeks were boosted prior to repeat CHMI at 24 weeks. Results At 12-week CHMI, 6/15 (40%) Group 1 (P=0.04), 3/15 (20%) Group 2 vs. 0/8 controls remained aparasitemic. At 24-week CHMI, 3/13 (23%) Group 3, 3/14 (21%) Group 4 vs. 0/8 controls remained aparasitemic (Groups 2-4, VE not significant). Post-boost, 9/14 (64%) vs. 0/8 controls remained aparasitemic (3/6 Group 1, P=0.025; 6/8 Group 2, P=0.002). Conclusions Four stacked, priming injections (multi-dose priming) showed 40% VE against heterologous CHMI, while dose escalation of PfSPZ using single dose priming was not significantly protective. Boosting unprotected subjects improved VE at 24 weeks to 64%.

scholarly journals Controlled Human Malaria Infection of Tanzanians by Intradermal Injection of Aseptic, Purified, Cryopreserved Plasmodium falciparum Sporozoites

2014 ◽  
Vol 91 (3) ◽  
pp. 471-480 ◽  
Author(s):  
Seif Shekalaghe ◽  
Mastidia Rutaihwa ◽  
Peter F. Billingsley ◽  
Mwajuma Chemba ◽  
Claudia A. Daubenberger ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Infection ◽  
Intradermal Injection ◽  
Human Malaria ◽  
Controlled Human Malaria Infection

scholarly journals Controlled Human Malaria Infection in Semi-Immune Kenyan Adults (CHMI-SIKA): a study protocol to investigate in vivo Plasmodium falciparum malaria parasite growth in the context of pre-existing immunity

2018 ◽  
Vol 3 ◽  
pp. 155 ◽  
Author(s):  
Melissa C. Kapulu ◽  
Patricia Njuguna ◽  
Mainga M. Hamaluba ◽  
Keyword(s):  
Plasmodium Falciparum ◽  
Immune Responses ◽  
Malaria Infection ◽  
Malaria Vaccine ◽  
Parasite Growth ◽  
Host Immunity ◽  
Human Malaria ◽  
Controlled Human Malaria Infection ◽  
Adult Volunteers

Malaria remains a major public health burden despite approval for implementation of a partially effective pre-erythrocytic malaria vaccine. There is an urgent need to accelerate development of a more effective multi-stage vaccine. Adults in malaria endemic areas may have substantial immunity provided by responses to the blood stages of malaria parasites, but field trials conducted on several blood-stage vaccines have not shown high levels of efficacy.  We will use controlled human malaria infection (CHMI) studies with malaria-exposed volunteers to identify correlations between immune responses and parasite growth rates in vivo.  Immune responses more strongly associated with control of parasite growth should be prioritized to accelerate malaria vaccine development. We aim to recruit up to 200 healthy adult volunteers from areas of differing malaria transmission in Kenya, and after confirming their health status through clinical examination and routine haematology and biochemistry, we will comprehensively characterize immunity to malaria using >100 blood-stage antigens. We will administer 3,200 aseptic, purified, cryopreserved Plasmodium falciparum sporozoites (PfSPZ Challenge) by direct venous inoculation. Serial quantitative polymerase chain reaction to measure parasite growth rate in vivo will be undertaken. Clinical and laboratory monitoring will be undertaken to ensure volunteer safety. In addition, we will also explore the perceptions and experiences of volunteers and other stakeholders in participating in a malaria volunteer infection study. Serum, plasma, peripheral blood mononuclear cells and extracted DNA will be stored to allow a comprehensive assessment of adaptive and innate host immunity. We will use CHMI in semi-immune adult volunteers to relate parasite growth outcomes with antibody responses and other markers of host immunity. Registration: ClinicalTrials.gov identifier NCT02739763.

scholarly journals Direct venous inoculation of Plasmodium falciparum sporozoites for controlled human malaria infection: a dose-finding trial in two centres

2015 ◽  
Vol 14 (1) ◽  
Author(s):  
Benjamin Mordmüller ◽  
Christian Supan ◽  
Kim Lee Sim ◽  
Gloria P Gómez-Pérez ◽  
Carmen Lucelly Ospina Salazar ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Infection ◽  
Dose Finding ◽  
Human Malaria ◽  
Controlled Human Malaria Infection
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