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Whole sporozoite immunization with Plasmodium falciparum strain NF135 in a randomized trial.
van der Boor, Saskia C; Alkema, Manon; van Gemert, Geert-Jan; Teelen, Karina; van de Vegte-Bolmer, Marga; Walk, Jona; van Crevel, Reinout; de Mast, Quirijn; Ockenhouse, Christian F; Sauerwein, Robert W; McCall, Matthew B B.
  • van der Boor SC; Department of Medical Microbiology, Radboud Center for Infectious Diseases, Radboud University Medical Center, Geert Grooteplein Zuid 28, 6525 GA, Nijmegen, The Netherlands.
  • Alkema M; Department of Medical Microbiology, Radboud Center for Infectious Diseases, Radboud University Medical Center, Geert Grooteplein Zuid 28, 6525 GA, Nijmegen, The Netherlands.
  • van Gemert GJ; Department of Medical Microbiology, Radboud Center for Infectious Diseases, Radboud University Medical Center, Geert Grooteplein Zuid 28, 6525 GA, Nijmegen, The Netherlands.
  • Teelen K; Department of Medical Microbiology, Radboud Center for Infectious Diseases, Radboud University Medical Center, Geert Grooteplein Zuid 28, 6525 GA, Nijmegen, The Netherlands.
  • van de Vegte-Bolmer M; Department of Medical Microbiology, Radboud Center for Infectious Diseases, Radboud University Medical Center, Geert Grooteplein Zuid 28, 6525 GA, Nijmegen, The Netherlands.
  • Walk J; Department of Medical Microbiology, Radboud Center for Infectious Diseases, Radboud University Medical Center, Geert Grooteplein Zuid 28, 6525 GA, Nijmegen, The Netherlands.
  • van Crevel R; Present affiliation: TropIQ Health Sciences, Transistorweg 5-C02, 6534 AT, Nijmegen, The Netherlands.
  • de Mast Q; Department of Internal Medicine, Radboud Center for Infectious Diseases, Radboud University Medical Centre, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands.
  • Ockenhouse CF; Department of Internal Medicine, Radboud Center for Infectious Diseases, Radboud University Medical Centre, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands.
  • Sauerwein RW; PATH Malaria Vaccine Initiative, Washington, DC, 20001, USA.
  • McCall MBB; Department of Medical Microbiology, Radboud Center for Infectious Diseases, Radboud University Medical Center, Geert Grooteplein Zuid 28, 6525 GA, Nijmegen, The Netherlands. R.Sauerwein@tropiq.nl.
BMC Med ; 21(1): 137, 2023 04 07.
Article in English | MEDLINE | ID: covidwho-2303147
ABSTRACT

BACKGROUND:

Whole sporozoite immunization under chemoprophylaxis (CPS regime) induces long-lasting sterile homologous protection in the controlled human malaria infection model using Plasmodium falciparum strain NF54. The relative proficiency of liver-stage parasite development may be an important factor determining immunization efficacy. Previous studies show that Plasmodium falciparum strain NF135 produces relatively high numbers of large liver-stage schizonts in vitro. Here, we evaluate this strain for use in CPS immunization regimes.

METHODS:

In a partially randomized, open-label study conducted at the Radboudumc, Nijmegen, the Netherlands, healthy, malaria-naïve adults were immunized by three rounds of fifteen or five NF135-infected mosquito bites under mefloquine prophylaxis (cohort A) or fifteen NF135-infected mosquito bites and presumptive treatment with artemether/lumefantrine (cohort B). Cohort A participants were exposed to a homologous challenge 19 weeks after immunization. The primary objective of the study was to evaluate the safety and tolerability of CPS immunizations with NF135.

RESULTS:

Relatively high liver-to-blood inocula were observed during immunization with NF135 in both cohorts. Eighteen of 30 (60%) high-dose participants and 3/10 (30%) low-dose participants experienced grade 3 adverse events 7 to 21 days following their first immunization. All cohort A participants and two participants in cohort B developed breakthrough blood-stage malaria infections during immunizations requiring rescue treatment. The resulting compromised immunizations induced modest sterile protection against homologous challenge in cohort A (5/17; 29%).

CONCLUSIONS:

These CPS regimes using NF135 were relatively poorly tolerated and frequently required rescue treatment, thereby compromising immunization efficiency and protective efficacy. Consequently, the full potential of NF135 sporozoites for induction of immune protection remains inconclusive. Nonetheless, the high liver-stage burden achieved by this strain highlights it as an interesting potential candidate for novel whole sporozoite immunization approaches. TRIAL REGISTRATION The trial was registered at ClinicalTrials.gov under identifier NCT03813108.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Malaria Vaccines / Insect Bites and Stings / Malaria / Antimalarials Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Topics: Vaccines Limits: Adult / Animals / Humans Language: English Journal: BMC Med Journal subject: Medicine Year: 2023 Document Type: Article Affiliation country: S12916-023-02788-9

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Malaria Vaccines / Insect Bites and Stings / Malaria / Antimalarials Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Topics: Vaccines Limits: Adult / Animals / Humans Language: English Journal: BMC Med Journal subject: Medicine Year: 2023 Document Type: Article Affiliation country: S12916-023-02788-9