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Multistage protective anti-CelTOS monoclonal antibodies with cross-species sterile protection against malaria

Author

Listed:
  • Wai Kwan Tang

    (National Institutes of Health)

  • Nichole D. Salinas

    (National Institutes of Health)

  • Surendra Kumar Kolli

    (University of South Florida)

  • Shulin Xu

    (University of South Florida)

  • Darya V. Urusova

    (Washington University School of Medicine)

  • Hirdesh Kumar

    (National Institutes of Health)

  • John R. Jimah

    (Washington University School of Medicine
    Princeton University)

  • Pradeep Annamalai Subramani

    (University of South Florida)

  • Madison M. Ogbondah

    (University of South Florida)

  • Samantha J. Barnes

    (University of South Florida)

  • John H. Adams

    (University of South Florida)

  • Niraj H. Tolia

    (National Institutes of Health)

Abstract

CelTOS is a malaria vaccine antigen that is conserved in Plasmodium and other apicomplexan parasites and plays a role in cell-traversal. The structural basis and mechanisms of CelTOS-induced protective immunity to parasites are unknown. Here, CelTOS-specific monoclonal antibodies (mAbs) 7g7 and 4h12 demonstrated multistage activity, protecting against liver infection and preventing parasite transmission to mosquitoes. Both mAbs demonstrated cross-species activity with sterile protection against in vivo challenge with transgenic parasites containing either P. falciparum or P. vivax CelTOS, and with transmission reducing activity against P. falciparum. The mAbs prevented CelTOS-mediated pore formation providing insight into the protective mechanisms. X-ray crystallography and mutant-library epitope mapping revealed two distinct broadly conserved neutralizing epitopes. 7g7 bound to a parallel dimer of CelTOS, while 4h12 bound to a novel antiparallel dimer architecture. These findings inform the design of antibody therapies and vaccines and raise the prospect of a single intervention to simultaneously combat P. falciparum and P. vivax malaria.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51701-2
    DOI: 10.1038/s41467-024-51701-2
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    References listed on IDEAS

    as
    1. Camila H. Coelho & Wai Kwan Tang & Martin Burkhardt & Jacob D. Galson & Olga Muratova & Nichole D. Salinas & Thiago Luiz Alves e Silva & Karine Reiter & Nicholas J. MacDonald & Vu Nguyen & Raul Herrer, 2021. "A human monoclonal antibody blocks malaria transmission and defines a highly conserved neutralizing epitope on gametes," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    2. 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.
    3. Stephen W. Scally & Brandon McLeod & Alexandre Bosch & Kazutoyo Miura & Qi Liang & Sean Carroll & Sini Reponen & Ngan Nguyen & Eldar Giladi & Sebastian Rämisch & Vidadi Yusibov & Allan Bradley & Franc, 2017. "Molecular definition of multiple sites of antibody inhibition of malaria transmission-blocking vaccine antigen Pfs25," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    4. Brandon McLeod & Kazutoyo Miura & Stephen W. Scally & Alexandre Bosch & Ngan Nguyen & Hanjun Shin & Dongkyoon Kim & Wayne Volkmuth & Sebastian Rämisch & Jessica A. Chichester & Stephen Streatfield & C, 2019. "Potent antibody lineage against malaria transmission elicited by human vaccination with Pfs25," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    5. Bruno E. Correia & John T. Bates & Rebecca J. Loomis & Gretchen Baneyx & Chris Carrico & Joseph G. Jardine & Peter Rupert & Colin Correnti & Oleksandr Kalyuzhniy & Vinayak Vittal & Mary J. Connell & E, 2014. "Proof of principle for epitope-focused vaccine design," Nature, Nature, vol. 507(7491), pages 201-206, March.
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