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).
Moorthy, V., Hamel, M. J. & Smith, P. G. Malaria vaccines for children: and now there are two. Lancet 403, 504–505 (2024).
Menard, R. et al. Circumsporozoite protein is required for development of malaria sporozoites in mosquitoes. Nature 385, 336–340 (1997).
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).
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).
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).
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).
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).
Mallory, K. L. et al. Messenger RNA expressing PfCSP induces functional, protective immune responses against malaria in mice. NPJ Vaccines. 6, 84 (2021).
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).
MacMillen, Z. et al. Accelerated prime-and-trap vaccine regimen in mice using repRNA-based CSP malaria vaccine. NPJ Vaccines. 9, 12 (2024).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
Singh, S. K. et al. Preclinical development of a Pfs230-Pfs48/45 chimeric malaria transmission-blocking vaccine. NPJ Vaccines. 6, 120 (2021).
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).
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).
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).
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).
Chakraborti, S. & Chakrabarti, P. Self-Assembly of Ferritin: Structure, Biological Function and Potential Applications in Nanotechnology. Adv. Exp. Med. Biol. 1174, 313–329 (2019).
Nguyen, B. & Tolia, N. H. Protein-based antigen presentation platforms for nanoparticle vaccines. NPJ Vaccines. 6, 70 (2021).
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).
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).
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).
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).
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).
Lu, C. et al. Design and assessment of TRAP-CSP fusion antigens as effective malaria vaccines. PLoS One 15, e0216260 (2020).
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).
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).
Yusuf, Y. et al. A Viral-Vectored Multi-Stage Malaria Vaccine Regimen With Protective and Transmission-Blocking Efficacies. Front Immunol. 10, 2412 (2019).
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).
Le, C. T. Combination vaccines: choices or chaos? A practitioner’s perspective. Clin. Infect. Dis. 33, S367–S371 (2001).
Tafreshi, S. H. Efficacy, safety, and formulation issues of the combined vaccines. Expert Rev. Vaccines. 19, 949–958 (2020).
Geens, R. et al. Biophysical characterization of the Plasmodium falciparum circumsporozoite protein’s N-terminal domain. Protein Sci. 33, e4852 (2024).
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).
Kundu, P. et al. Structural delineation of potent transmission-blocking epitope I on malaria antigen Pfs48/45. Nat. Commun. 9, 4458 (2018).
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).
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).
Langowski, M. D. et al. Elicitation of liver-stage immunity by nanoparticle immunogens displaying P. falciparum CSP-derived antigens. NPJ Vaccines. 10, 87 (2025).
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).
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).
Hura, G. L. et al. Robust, high-throughput solution structural analyses by small angle X-ray scattering (SAXS). Nat. Methods 6, 606–612 (2009).
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).
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).
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).
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).
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).
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).