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Abstract

Pfs25 is a malaria transmission-blocking vaccine antigen candidate, but its apparently limited immunogenicity in humans has hindered clinical development. Here, we show that recombinant, polyhistidine-tagged (his-tagged) Pfs25 can be mixed at the time of immunization with pre-formed liposomes containing cobalt porphyrin–phospholipid, resulting in spontaneous nanoliposome antigen particleization (SNAP). Antigens are stably presented in uniformly orientated display via his-tag insertion in the cobalt porphyrin–phospholipid bilayer, without covalent modification or disruption of antigen conformation. SNAP immunization of mice and rabbits is well tolerated with minimal local reactogenicity, and results in orders-of-magnitude higher functional antibody generation compared with other ‘mix-and-inject’ adjuvants. Serum-stable antigen binding during transit to draining lymph nodes leads to enhanced antigen uptake by phagocytic antigen-presenting cells, with subsequent generation of long-lived, antigen-specific plasma cells. Seamless multiplexing with four additional his-tagged Plasmodium falciparum polypeptides induces strong and balanced antibody production, illustrating the simplicity of developing multistage particulate vaccines with SNAP immunization.

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Acknowledgements

This study was supported by PATH’s Malaria Vaccine Initiative, and grants from the National Institutes of Health (R21AI122964 and DP5OD017898) and the intramural programme of the National Institute of Allergy and Infectious Diseases/NIH. The authors acknowledge assistance from G. Mlambo and A. Tripathi with immunofluorescence assays, and input from C. Alving and A. Birkett.

Author information

Affiliations

  1. Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY, USA

    • Wei-Chiao Huang
    • , Cuiyan Lin
    • , Kevin A. Carter
    • , Jumin Geng
    • , Xuedan He
    • , Upendra Chitgupi
    • , Jasmin Federizon
    • , Boyang Sun
    •  & Jonathan F. Lovell
  2. Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA

    • Bingbing Deng
    • , Carole A. Long
    •  & Kazutoyo Miura
  3. Department of Anatomy and Cell Biology, McGill University Montreal, Quebec, Canada

    • Aida Razi
    •  & Joaquin Ortega
  4. Walter Reed Army Institute of Research, Silver Spring, MD, USA

    • Sheetij Dutta
  5. PATH’s Malaria Vaccine Initiative, Washington, DC, USA

    • C. Richter King
    •  & Shwu-Maan Lee

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Contributions

W.-C.H., C.R.K., S.-M.L. and J.F.L conceived the project. W.-C.H., K.M., S.-M.L. and J.F.L. designed most of the experiments. W.-C.H. and J.F.L. wrote the manuscript. W.-C.H., C.L. and J.G. performed the animal experiments. W.-C.H., C.L., B.D., C.A.L. and K.M. performed and interpreted the ELISA and SMFA experiments. A.R. and J.O. performed transmission electron cryomicroscopy. W.-C.H., K.A.C., C.L., X.H. and B.S. produced and characterized the liposomes. X.H. performed the splenocyte studies. U.C. and W.-C.H. produced fluorescently labelled antigens. J.F. performed the circular dichroism studies. S.D. and S.-M.L. produced the antigens.

Competing interests

W.-C.H., C.R.K., S.-M.L., J.G. and J.F.L are named inventors on a patent application describing this technology. All other authors declare no competing financial interests.

Corresponding author

Correspondence to Jonathan F. Lovell.

Supplementary information

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    Supplementary Methods, Supplementary Figures 1–20 and Supplementary Tables 1–5

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DOI

https://doi.org/10.1038/s41565-018-0271-3

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