IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-40878-7.html
   My bibliography  Save this article

Structure-based design of a strain transcending AMA1-RON2L malaria vaccine

Author

Listed:
  • Palak N. Patel

    (National Institutes of Health)

  • Thayne H. Dickey

    (National Institutes of Health)

  • Ababacar Diouf

    (National Institutes of Health)

  • Nichole D. Salinas

    (National Institutes of Health)

  • Holly McAleese

    (National Institutes of Health)

  • Tarik Ouahes

    (National Institutes of Health)

  • Carole A. Long

    (National Institutes of Health)

  • Kazutoyo Miura

    (National Institutes of Health)

  • Lynn E. Lambert

    (National Institutes of Health)

  • Niraj H. Tolia

    (National Institutes of Health)

Abstract

Apical membrane antigen 1 (AMA1) is a key malaria vaccine candidate and target of neutralizing antibodies. AMA1 binds to a loop in rhoptry neck protein 2 (RON2L) to form the moving junction during parasite invasion of host cells, and this complex is conserved among apicomplexan parasites. AMA1-RON2L complex immunization achieves higher growth inhibitory activity than AMA1 alone and protects mice against Plasmodium yoelii challenge. Here, three single-component AMA1-RON2L immunogens were designed that retain the structure of the two-component AMA1-RON2L complex: one structure-based design (SBD1) and two insertion fusions. All immunogens elicited high antibody titers with potent growth inhibitory activity, yet these antibodies did not block RON2L binding to AMA1. The SBD1 immunogen induced significantly more potent strain-transcending neutralizing antibody responses against diverse strains of Plasmodium falciparum than AMA1 or AMA1-RON2L complex vaccination. This indicates that SBD1 directs neutralizing antibody responses to strain-transcending epitopes in AMA1 that are independent of RON2L binding. This work underscores the importance of neutralization mechanisms that are distinct from RON2 blockade. The stable single-component SBD1 immunogen elicits potent strain-transcending protection that may drive the development of next-generation vaccines for improved malaria and apicomplexan parasite control.

Suggested Citation

  • Palak N. Patel & Thayne H. Dickey & Ababacar Diouf & Nichole D. Salinas & Holly McAleese & Tarik Ouahes & Carole A. Long & Kazutoyo Miura & Lynn E. Lambert & Niraj H. Tolia, 2023. "Structure-based design of a strain transcending AMA1-RON2L malaria vaccine," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40878-7
    DOI: 10.1038/s41467-023-40878-7
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-40878-7
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-40878-7?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
    ---><---

    References listed on IDEAS

    as
    1. Palak N. Patel & Thayne H. Dickey & Christine S. Hopp & Ababacar Diouf & Wai Kwan Tang & Carole A. Long & Kazutoyo Miura & Peter D. Crompton & Niraj H. Tolia, 2022. "Neutralizing and interfering human antibodies define the structural and mechanistic basis for antigenic diversion," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    2. Mauld H. Lamarque & Magali Roques & Marie Kong-Hap & Michelle L. Tonkin & George Rugarabamu & Jean-Baptiste Marq & Diana M. Penarete-Vargas & Martin J. Boulanger & Dominique Soldati-Favre & Maryse Leb, 2014. "Plasticity and redundancy among AMA–RON pairs ensure host cell entry of Toxoplasma parasites," Nature Communications, Nature, vol. 5(1), pages 1-13, September.
    Full references (including those not matched with items on IDEAS)

    Citations

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


    Cited by:

    1. Wai Kwan Tang & Nichole D. Salinas & Surendra Kumar Kolli & Shulin Xu & Darya V. Urusova & Hirdesh Kumar & John R. Jimah & Pradeep Annamalai Subramani & Madison M. Ogbondah & Samantha J. Barnes & John, 2024. "Multistage protective anti-CelTOS monoclonal antibodies with cross-species sterile protection against malaria," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Dimuthu Angage & Jill Chmielewski & Janesha C. Maddumage & Eva Hesping & Sabrina Caiazzo & Keng Heng Lai & Lee Ming Yeoh & Joseph Menassa & D. Herbert Opi & Callum Cairns & Hamsa Puthalakath & James G, 2024. "A broadly cross-reactive i-body to AMA1 potently inhibits blood and liver stages of Plasmodium parasites," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.

      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:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40878-7. 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.

      If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with 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.