Whole sporozoite immunization with Plasmodium falciparum strain NF135 in a randomized trial
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 imp...
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| Format: | Article |
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BMC
2023-04-01
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| Series: | BMC Medicine |
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| Online Access: | https://doi.org/10.1186/s12916-023-02788-9 |
| _version_ | 1797850017911799808 |
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| author | Saskia C. van der Boor Manon Alkema Geert-Jan van Gemert Karina Teelen Marga van de Vegte-Bolmer Jona Walk Reinout van Crevel Quirijn de Mast Christian F. Ockenhouse Robert W. Sauerwein Matthew B. B. McCall |
| author_facet | Saskia C. van der Boor Manon Alkema Geert-Jan van Gemert Karina Teelen Marga van de Vegte-Bolmer Jona Walk Reinout van Crevel Quirijn de Mast Christian F. Ockenhouse Robert W. Sauerwein Matthew B. B. McCall |
| author_sort | Saskia C. van der Boor |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T18:53:34Z |
| format | Article |
| id | doaj.art-28495ce92cd3443cb2435728df4cd2f2 |
| institution | Directory Open Access Journal |
| issn | 1741-7015 |
| language | English |
| last_indexed | 2024-04-09T18:53:34Z |
| publishDate | 2023-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medicine |
| spelling | doaj.art-28495ce92cd3443cb2435728df4cd2f22023-04-09T11:18:41ZengBMCBMC Medicine1741-70152023-04-0121111410.1186/s12916-023-02788-9Whole sporozoite immunization with Plasmodium falciparum strain NF135 in a randomized trialSaskia C. van der Boor0Manon Alkema1Geert-Jan van Gemert2Karina Teelen3Marga van de Vegte-Bolmer4Jona Walk5Reinout van Crevel6Quirijn de Mast7Christian F. Ockenhouse8Robert W. Sauerwein9Matthew B. B. McCall10Department of Medical Microbiology, Radboud Center for Infectious Diseases, Radboud University Medical CenterDepartment of Medical Microbiology, Radboud Center for Infectious Diseases, Radboud University Medical CenterDepartment of Medical Microbiology, Radboud Center for Infectious Diseases, Radboud University Medical CenterDepartment of Medical Microbiology, Radboud Center for Infectious Diseases, Radboud University Medical CenterDepartment of Medical Microbiology, Radboud Center for Infectious Diseases, Radboud University Medical CenterDepartment of Medical Microbiology, Radboud Center for Infectious Diseases, Radboud University Medical CenterDepartment of Internal Medicine, Radboud Center for Infectious Diseases, Radboud University Medical CentreDepartment of Internal Medicine, Radboud Center for Infectious Diseases, Radboud University Medical CentrePATH Malaria Vaccine InitiativeDepartment of Medical Microbiology, Radboud Center for Infectious Diseases, Radboud University Medical CenterDepartment of Medical Microbiology, Radboud Center for Infectious Diseases, Radboud University Medical CenterAbstract 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.https://doi.org/10.1186/s12916-023-02788-9MalariaPlasmodium falciparumWhole sporozoite immunizationVaccine-induced protectionNF135 |
| spellingShingle | Saskia C. van der Boor Manon Alkema Geert-Jan van Gemert Karina Teelen Marga van de Vegte-Bolmer Jona Walk Reinout van Crevel Quirijn de Mast Christian F. Ockenhouse Robert W. Sauerwein Matthew B. B. McCall Whole sporozoite immunization with Plasmodium falciparum strain NF135 in a randomized trial BMC Medicine Malaria Plasmodium falciparum Whole sporozoite immunization Vaccine-induced protection NF135 |
| title | Whole sporozoite immunization with Plasmodium falciparum strain NF135 in a randomized trial |
| title_full | Whole sporozoite immunization with Plasmodium falciparum strain NF135 in a randomized trial |
| title_fullStr | Whole sporozoite immunization with Plasmodium falciparum strain NF135 in a randomized trial |
| title_full_unstemmed | Whole sporozoite immunization with Plasmodium falciparum strain NF135 in a randomized trial |
| title_short | Whole sporozoite immunization with Plasmodium falciparum strain NF135 in a randomized trial |
| title_sort | whole sporozoite immunization with plasmodium falciparum strain nf135 in a randomized trial |
| topic | Malaria Plasmodium falciparum Whole sporozoite immunization Vaccine-induced protection NF135 |
| url | https://doi.org/10.1186/s12916-023-02788-9 |
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