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A combined designed CSP and Pfs48/45 infection and transmission blocking vaccine for malaria

  • WHO. World malaria report 2023. (2023).

  • Venkatesan, P. The 2023 WHO World malaria report. Lancet Microbe. https://doi.org/10.1016/S2666-5247(24)00016-8 (2024).

  • WHO. WHO prequalifies a second malaria vaccine, a significant milestone in prevention of the disease., https://www.who.int/news/item/21-12-2023-who-prequalifies-a-second-malaria-vaccine-a-significant-milestone-in-prevention-of-the-disease (2023).

  • Adepoju, P. Malaria community welcomes WHO vaccine approval. Lancet 402, 1316 (2023).

    Article 
    PubMed 

    Google Scholar
     

  • Moorthy, V., Hamel, M. J. & Smith, P. G. Malaria vaccines for children: and now there are two. Lancet 403, 504–505 (2024).

    Article 
    PubMed 

    Google Scholar
     

  • Menard, R. et al. Circumsporozoite protein is required for development of malaria sporozoites in mosquitoes. Nature 385, 336–340 (1997).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Tewari, R., Spaccapelo, R., Bistoni, F., Holder, A. A. & Crisanti, A. Function of region I and II adhesive motifs of Plasmodium falciparum circumsporozoite protein in sporozoite motility and infectivity. J. Biol. Chem. 277, 47613–47618 (2002).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Cerami, C. et al. The basolateral domain of the hepatocyte plasma membrane bears receptors for the circumsporozoite protein of Plasmodium falciparum sporozoites. Cell 70, 1021–1033 (1992).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Gordon, D. M. et al. Safety, immunogenicity, and efficacy of a recombinantly produced Plasmodium falciparum circumsporozoite protein-hepatitis B surface antigen subunit vaccine. J. Infect. Dis. 171, 1576–1585 (1995).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Collins, K. A. et al. Ultra-low dose immunization and multi-component vaccination strategies enhance protection against malaria in mice. Sci. Rep. 11, 10792 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kaba, S. A. et al. Self-assembling protein nanoparticles with built-in flagellin domains increases protective efficacy of a Plasmodium falciparum based vaccine. Vaccine 36, 906–914 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Mallory, K. L. et al. Messenger RNA expressing PfCSP induces functional, protective immune responses against malaria in mice. NPJ Vaccines. 6, 84 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hayashi, C. T. H. et al. mRNA-LNP expressing PfCSP and Pfs25 vaccine candidates targeting infection and transmission of Plasmodium falciparum. NPJ Vaccines. 7, 155 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • MacMillen, Z. et al. Accelerated prime-and-trap vaccine regimen in mice using repRNA-based CSP malaria vaccine. NPJ Vaccines. 9, 12 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cao, Y. et al. Effective Functional Immunogenicity of a DNA Vaccine Combination Delivered via In Vivo Electroporation Targeting Malaria Infection and Transmission. Vaccines (Basel). 12, https://doi.org/10.3390/vaccines12090994 (2024).

  • Langowski, M. D. et al. Optimization of a Plasmodium falciparum circumsporozoite protein repeat vaccine using the tobacco mosaic virus platform. Proc. Natl Acad. Sci. USA. 117, 3114–3122 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wang, L. T. et al. A Potent Anti-Malarial Human Monoclonal Antibody Targets Circumsporozoite Protein Minor Repeats and Neutralizes Sporozoites in the Liver. Immunity 53, 733–744.e738 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sherrard-Smith, E. et al. Synergy in anti-malarial pre-erythrocytic and transmission-blocking antibodies is achieved by reducing parasite density. Elife 7, https://doi.org/10.7554/eLife.35213 (2018).

  • Sauerwein, R. W., Plieskatt, J. & Theisen, M. 40 Years of Pfs48/45 Research as a Transmission-Blocking Vaccine Target of Plasmodium falciparum Malaria. Am. J. Trop. Med. Hyg. https://doi.org/10.4269/ajtmh.21-1320 (2022).

  • Van Dijk, M. R. et al. A central role for P48/45 in malaria parasite male gamete fertility. Cell 104, 153–164 (2001).

    Article 
    PubMed 

    Google Scholar
     

  • Fabra-Garcia, A. et al. Highly potent, naturally acquired human monoclonal antibodies against Pfs48/45 block Plasmodium falciparum transmission to mosquitoes. Immunity 56, 406–419.e407 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chowdhury, D. R., Angov, E., Kariuki, T. & Kumar, N. A potent malaria transmission blocking vaccine based on codon harmonized full length Pfs48/45 expressed in Escherichia coli. PLoS One 4, e6352 (2009).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lee, S. M. et al. A C-terminal Pfs48/45 malaria transmission-blocking vaccine candidate produced in the baculovirus expression system. Sci. Rep. 10, 395 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Milek, R. L. et al. Plasmodium falciparum: heterologous synthesis of the transmission-blocking vaccine candidate Pfs48/45 in recombinant vaccinia virus-infected cells. Exp. Parasitol. 90, 165–174 (1998).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Milek, R. L., Stunnenberg, H. G. & Konings, R. N. Assembly and expression of a synthetic gene encoding the antigen Pfs48/45 of the human malaria parasite Plasmodium falciparum in yeast. Vaccine 18, 1402–1411 (2000).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Jones, C. S. et al. Heterologous expression of the C-terminal antigenic domain of the malaria vaccine candidate Pfs48/45 in the green algae Chlamydomonas reinhardtii. Appl. Microbiol. Biotechnol. 97, 1987–1995 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Mamedov, T. et al. A Plant-Produced in vivo deglycosylated full-length Pfs48/45 as a Transmission-Blocking Vaccine Candidate against malaria. Sci. Rep. 9, 9868 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Theisen, M., Jore, M. M. & Sauerwein, R. Towards clinical development of a Pfs48/45-based transmission blocking malaria vaccine. Expert Rev. Vaccines. 16, 329–336 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lennartz, F. et al. Structural basis for recognition of the malaria vaccine candidate Pfs48/45 by a transmission blocking antibody. Nat. Commun. 9, 3822 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Roeffen, W. et al. Transmission-blocking activity of antibodies to Plasmodium falciparum GLURP.10C chimeric protein formulated in different adjuvants. Malar. J. 14, 443 (2015).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Singh, S. K. et al. A Plasmodium falciparum 48/45 single epitope R0.6C subunit protein elicits high levels of transmission blocking antibodies. Vaccine 33, 1981–1986 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Singh, S. K. et al. A Reproducible and Scalable Process for Manufacturing a Pfs48/45 Based Plasmodium falciparum Transmission-Blocking Vaccine. Front Immunol. 11, 606266 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Singh, S. K. et al. Preclinical development of a Pfs230-Pfs48/45 chimeric malaria transmission-blocking vaccine. NPJ Vaccines. 6, 120 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Naghizadeh, M. et al. Magnitude and durability of ProC6C-AlOH/Matrix-M(tm) vaccine-induced malaria transmission-blocking antibodies in Burkinabe adults from a Phase 1 randomized trial. Hum. Vaccin Immunother. 21, 2488075 (2025).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Alkema, M. et al. A Pfs48/45-based vaccine to block Plasmodium falciparum transmission: phase 1, open-label, clinical trial. BMC Med. 22, 170 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tiono, A. B. et al. A randomized first-in-human phase I trial of differentially adjuvanted Pfs48/45 malaria vaccines in Burkinabe adults. J. Clin. Invest. 134, https://doi.org/10.1172/JCI175707 (2024).

  • Dickey, T. H. et al. Design of the SARS-CoV-2 RBD vaccine antigen improves neutralizing antibody response. Sci. Adv. 8, eabq8276 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dickey, T. H. et al. Design of a stabilized non-glycosylated Pfs48/45 antigen enables a potent malaria transmission-blocking nanoparticle vaccine. NPJ Vaccines. 8, 20 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chakraborti, S. & Chakrabarti, P. Self-Assembly of Ferritin: Structure, Biological Function and Potential Applications in Nanotechnology. Adv. Exp. Med. Biol. 1174, 313–329 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Nguyen, B. & Tolia, N. H. Protein-based antigen presentation platforms for nanoparticle vaccines. NPJ Vaccines. 6, 70 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ludwig, J. et al. Glycosylated nanoparticle-based PfCSP vaccine confers long-lasting antibody responses and sterile protection in mouse malaria model. NPJ Vaccines. 8, 52 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rodrigues, M. Q., Alves, P. M. & Roldao, A. Functionalizing Ferritin Nanoparticles for Vaccine Development. Pharmaceutics 13, https://doi.org/10.3390/pharmaceutics13101621 (2021).

  • Houser, K. V. et al. Safety and immunogenicity of a ferritin nanoparticle H2 influenza vaccine in healthy adults: a phase 1 trial. Nat. Med. 28, 383–391 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Widge, A. T. et al. An influenza hemagglutinin stem nanoparticle vaccine induces cross-group 1 neutralizing antibodies in healthy adults. Sci. Transl. Med. 15, eade4790 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Andrews, S. F. et al. An influenza H1 hemagglutinin stem-only immunogen elicits a broadly cross-reactive B cell response in humans. Sci. Transl. Med. 15, eade4976 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ober Shepherd, B. L. et al. SARS-CoV-2 recombinant spike ferritin nanoparticle vaccine adjuvanted with Army Liposome Formulation containing monophosphoryl lipid A and QS-21: a phase 1, randomised, double-blind, placebo-controlled, first-in-human clinical trial. Lancet Microbe 5, e581–e593 (2024).

    Article 
    PubMed 

    Google Scholar
     

  • Lu, C. et al. Design and assessment of TRAP-CSP fusion antigens as effective malaria vaccines. PLoS One 15, e0216260 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gao, W. et al. A dual-antigen malaria vaccine targeting Pb22 and Pbg37 was able to induce robust transmission-blocking activity. Parasit. Vectors 16, 455 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Huang, W. C. et al. Vaccine co-display of CSP and Pfs230 on liposomes targeting two Plasmodium falciparum differentiation stages. Commun. Biol. 5, 773 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yusuf, Y. et al. A Viral-Vectored Multi-Stage Malaria Vaccine Regimen With Protective and Transmission-Blocking Efficacies. Front Immunol. 10, 2412 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Baptista, B. O. et al. Naturally acquired antibody response to a Plasmodium falciparum chimeric vaccine candidate GMZ2.6c and its components (MSP-3, GLURP, and Pfs48/45) in individuals living in Brazilian malaria-endemic areas. Malar. J. 21, 6 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Le, C. T. Combination vaccines: choices or chaos? A practitioner’s perspective. Clin. Infect. Dis. 33, S367–S371 (2001).

    Article 
    PubMed 

    Google Scholar
     

  • Tafreshi, S. H. Efficacy, safety, and formulation issues of the combined vaccines. Expert Rev. Vaccines. 19, 949–958 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Geens, R. et al. Biophysical characterization of the Plasmodium falciparum circumsporozoite protein’s N-terminal domain. Protein Sci. 33, e4852 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Pendyala, G., Calvo-Calle, J. M., Moreno, A. & Kane, R. S. A multivalent Plasmodium falciparum circumsporozoite protein-based nanoparticle malaria vaccine elicits a robust and durable antibody response against the junctional epitope and the major repeats. Bioeng. Transl. Med. 8, e10514 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kundu, P. et al. Structural delineation of potent transmission-blocking epitope I on malaria antigen Pfs48/45. Nat. Commun. 9, 4458 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Van der Boor, S. C. et al. Safety, tolerability, and Plasmodium falciparum transmission-reducing activity of monoclonal antibody TB31F: a single-centre, open-label, first-in-human, dose-escalation, phase 1 trial in healthy malaria-naive adults. Lancet Infect. Dis. 22, 1596–1605 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kisalu, N. K. et al. A human monoclonal antibody prevents malaria infection by targeting a new site of vulnerability on the parasite. Nat. Med. 24, 408–416 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Langowski, M. D. et al. Elicitation of liver-stage immunity by nanoparticle immunogens displaying P. falciparum CSP-derived antigens. NPJ Vaccines. 10, 87 (2025).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Schneider, C. G. et al. Orientation of Antigen Display on Self-Assembling Protein Nanoparticles Influences Immunogenicity. Vaccines (Basel). 9, https://doi.org/10.3390/vaccines9020103 (2021).

  • Kanekiyo, M. et al. Rational Design of an Epstein-Barr Virus Vaccine Targeting the Receptor-Binding Site. Cell 162, 1090–1100 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Classen, S. et al. Implementation and performance of SIBYLS: a dual endstation small-angle X-ray scattering and macromolecular crystallography beamline at the Advanced Light Source. J. Appl Crystallogr. 46, 1–13 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hura, G. L. et al. Robust, high-throughput solution structural analyses by small angle X-ray scattering (SAXS). Nat. Methods 6, 606–612 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dyer, K. N. et al. High-throughput SAXS for the characterization of biomolecules in solution: a practical approach. Methods Mol. Biol. 1091, 245–258 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Manalastas-Cantos, K. et al. ATSAS 3.0: expanded functionality and new tools for small-angle scattering data analysis. J. Appl. Crystallogr. 54, 343–355 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zivanov, J. et al. New tools for automated high-resolution cryo-EM structure determination in RELION-3. Elife 7, https://doi.org/10.7554/eLife.42166 (2018).

  • Salman, A. M. et al. Generation of Transgenic Rodent Malaria Parasites Expressing Human Malaria Parasite Proteins. Methods Mol. Biol. 1325, 257–286 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Rodriguez-Galan, A. et al. An in vitro assay to measure antibody-mediated inhibition of P. berghei sporozoite invasion against P. falciparum antigens. Sci. Rep. 7, 17011 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Conteh, S. et al. Dynamics and Outcomes of Plasmodium Infections in Grammomys surdaster (Grammomys dolichurus) Thicket Rats versus Inbred Mice. Am. J. Trop. Med Hyg. 103, 1893–1901 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Miura, K. et al. Qualification of standard membrane-feeding assay with Plasmodium falciparum malaria and potential improvements for future assays. PLoS One 8, e57909 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

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