IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v595y2021i7866d10.1038_s41586-021-03684-z.html
   My bibliography  Save this article

Two chemoattenuated PfSPZ malaria vaccines induce sterile hepatic immunity

Author

Listed:
  • Agnes Mwakingwe-Omari

    (National Institutes of Health
    Center for Vaccine Research, GlaxoSmithKline)

  • Sara A. Healy

    (National Institutes of Health)

  • Jacquelyn Lane

    (National Institutes of Health)

  • David M. Cook

    (National Institutes of Health)

  • Sahand Kalhori

    (National Institutes of Health)

  • Charles Wyatt

    (National Institutes of Health)

  • Aarti Kolluri

    (National Institutes of Health)

  • Omely Marte-Salcedo

    (National Institutes of Health)

  • Alemush Imeru

    (National Institutes of Health)

  • Martha Nason

    (National Institute of Allergy and Infectious Diseases)

  • Lei K. Ding

    (National Institutes of Health)

  • Hope Decederfelt

    (National Institutes of Health)

  • Junhui Duan

    (National Institutes of Health)

  • Jillian Neal

    (National Institutes of Health)

  • Jacob Raiten

    (National Institutes of Health)

  • Grace Lee

    (National Institutes of Health)

  • Jen C. C. Hume

    (National Institutes of Health)

  • Jihyun E. Jeon

    (National Institutes of Health)

  • Ijeoma Ikpeama

    (Clinical Center, National Institutes of Health)

  • Natasha KC

    (Sanaria
    Protein Potential)

  • Sumana Chakravarty

    (Sanaria)

  • Tooba Murshedkar

    (Sanaria)

  • L. W. Preston Church

    (Sanaria)

  • Anita Manoj

    (Sanaria)

  • Anusha Gunasekera

    (Sanaria)

  • Charles Anderson

    (National Institutes of Health)

  • Sean C. Murphy

    (University of Washington
    University of Washington
    Fred Hutch Cancer Research Center
    University of Washington)

  • Sandra March

    (Massachusetts Institute of Technology)

  • Sangeeta N. Bhatia

    (Massachusetts Institute of Technology
    Koch Institute for Integrative Cancer Research
    Broad Institute
    Howard Hughes Medical Institute)

  • Eric R. James

    (Sanaria)

  • Peter F. Billingsley

    (Sanaria)

  • B. Kim Lee Sim

    (Sanaria
    Protein Potential)

  • Thomas L. Richie

    (Sanaria)

  • Irfan Zaidi

    (National Institutes of Health)

  • Stephen L. Hoffman

    (Sanaria)

  • Patrick E. Duffy

    (National Institutes of Health)

Abstract

The global decline in malaria has stalled1, emphasizing the need for vaccines that induce durable sterilizing immunity. Here we optimized regimens for chemoprophylaxis vaccination (CVac), for which aseptic, purified, cryopreserved, infectious Plasmodium falciparum sporozoites (PfSPZ) were inoculated under prophylactic cover with pyrimethamine (PYR) (Sanaria PfSPZ-CVac(PYR)) or chloroquine (CQ) (PfSPZ-CVac(CQ))—which kill liver-stage and blood-stage parasites, respectively—and we assessed vaccine efficacy against homologous (that is, the same strain as the vaccine) and heterologous (a different strain) controlled human malaria infection (CHMI) three months after immunization ( https://clinicaltrials.gov/ , NCT02511054 and NCT03083847). We report that a fourfold increase in the dose of PfSPZ-CVac(PYR) from 5.12 × 104 to 2 × 105 PfSPZs transformed a minimal vaccine efficacy (low dose, two out of nine (22.2%) participants protected against homologous CHMI), to a high-level vaccine efficacy with seven out of eight (87.5%) individuals protected against homologous and seven out of nine (77.8%) protected against heterologous CHMI. Increased protection was associated with Vδ2 γδ T cell and antibody responses. At the higher dose, PfSPZ-CVac(CQ) protected six out of six (100%) participants against heterologous CHMI three months after immunization. All homologous (four out of four) and heterologous (eight out of eight) infectivity control participants showed parasitaemia. PfSPZ-CVac(CQ) and PfSPZ-CVac(PYR) induced a durable, sterile vaccine efficacy against a heterologous South American strain of P. falciparum, which has a genome and predicted CD8 T cell immunome that differs more strongly from the African vaccine strain than other analysed African P. falciparum strains.

Suggested Citation

  • Agnes Mwakingwe-Omari & Sara A. Healy & Jacquelyn Lane & David M. Cook & Sahand Kalhori & Charles Wyatt & Aarti Kolluri & Omely Marte-Salcedo & Alemush Imeru & Martha Nason & Lei K. Ding & Hope Decede, 2021. "Two chemoattenuated PfSPZ malaria vaccines induce sterile hepatic immunity," Nature, Nature, vol. 595(7866), pages 289-294, July.
  • Handle: RePEc:nat:nature:v:595:y:2021:i:7866:d:10.1038_s41586-021-03684-z
    DOI: 10.1038/s41586-021-03684-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-021-03684-z
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.

    File URL: https://libkey.io/10.1038/s41586-021-03684-z?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Patricia Ferrer & Andrea A. Berry & Allison N. Bucsan & Surendra K. Prajapati & Karthik Krishnan & Michelle C. Barbeau & David M. Rickert & Sandra Mendoza Guerrero & Miho Usui & Yonas Abebe & Asha Pat, 2024. "Repeat controlled human Plasmodium falciparum infections delay bloodstream patency and reduce symptoms," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    2. Prasanna Jagannathan & Abel Kakuru, 2022. "Malaria in 2022: Increasing challenges, cautious optimism," Nature Communications, Nature, vol. 13(1), pages 1-3, December.
    3. Joana C. Silva & Ankit Dwivedi & Kara A. Moser & Mahamadou S. Sissoko & Judith E. Epstein & Sara A. Healy & Kirsten E. Lyke & Benjamin Mordmüller & Peter G. Kremsner & Patrick E. Duffy & Tooba Murshed, 2022. "Plasmodium falciparum 7G8 challenge provides conservative prediction of efficacy of PfNF54-based PfSPZ Vaccine in Africa," Nature Communications, Nature, vol. 13(1), pages 1-9, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:595:y:2021:i:7866:d:10.1038_s41586-021-03684-z. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.