{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T21:48:30Z","timestamp":1787003310961,"version":"build-2736575974"},"reference-count":55,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":66,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100030692","name":"Intramural Research Program","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100030692","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["npj Vaccines"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Repetitive display of the major repeats of the\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    circumsporozoite protein (PfCSP) is the basis for two WHO-recommended vaccines: RTS,S\/AS01 and R21\/Matrix-M. Recently, however, the CIS43 monoclonal antibody that preferentially targets the junctional region of PfCSP has been shown to be highly protective in humans, highlighting its junctional epitope as a key vaccine target. Here, we develop a vaccine based on tandem repeats of the junctional epitope displayed on a self-assembling nanoparticle and compare this CIS43-based junctional vaccine alone or in combination with the benchmark R21 vaccine, using both B cell analysis and monoclonal antibody isolation to define targeting of the immune response. Comparable reduction in liver burden was observed following vaccination with the best junctional vaccine and R21 at a dose of 1\u2009\u03bcg. At a dose of 0.25\u2009\u03bcg, a modest reduction of malaria liver burden with the junctional vaccine was observed compared to R21. Further, combining the junctional and R21 vaccines did not yield substantial improvement, although a modest trend was observed. While the R21 vaccine elicited antibodies primarily against the major repeats, the junctional vaccine elicited antibodies against both junctional and major repeat regions. In vivo B cell analysis and isolation of monoclonal antibodies confirmed differences in vaccine-induced antibody specificities. Altogether, these data suggest the nanoparticle-formatted tandem-repeated CIS43-junctional vaccine to be a promising approach to broaden immunity against malaria, either as a standalone intervention or in combination with R21.\n                  <\/jats:p>","DOI":"10.1038\/s41541-026-01455-3","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T13:05:13Z","timestamp":1777295113000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Protective immunity against malaria by a nanoparticle CIS43-based junctional vaccine alone or in combination with R21"],"prefix":"10.1038","volume":"11","author":[{"given":"Prabhanshu","family":"Tripathi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ja-Hyun","family":"Koo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lais Da","family":"Silva Pereira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlon","family":"Dillon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baoshan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariah","family":"Lofgren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katelyn T.","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I-Ting","family":"Teng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Bonilla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Kerscher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wing-Pui","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy R.","family":"Henry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler","family":"Stephens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaroslav","family":"Tsybovsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie R.","family":"Weldon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel C.","family":"Douek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore C.","family":"Pierson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Facundo D.","family":"Batista","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azza H.","family":"Idris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Seder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter D.","family":"Kwong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongqing","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,27]]},"reference":[{"key":"1455_CR1","unstructured":"World malaria report 2024. https:\/\/www.who.int\/publications\/i\/item\/9789240104440 (2024)."},{"key":"1455_CR2","doi-asserted-by":"publisher","first-page":"1947","DOI":"10.1084\/jem.157.6.1947","volume":"157","author":"F Zavala","year":"1983","unstructured":"Zavala, F., Cochrane, A. H., Nardin, E. H., Nussenzweig, R. S. & Nussenzweig, V. Circumsporozoite proteins of malaria parasites contain a single immunodominant region with two or more identical epitopes. J. Exp. Med. 157, 1947\u20131957 (1983).","journal-title":"J. Exp. Med."},{"key":"1455_CR3","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1126\/science.6204383","volume":"225","author":"JB Dame","year":"1984","unstructured":"Dame, J. B. et al. Structure of the gene encoding the immunodominant surface antigen on the sporozoite of the human malaria parasite Plasmodium falciparum. Science 225, 593\u2013599 (1984).","journal-title":"Science"},{"key":"1455_CR4","unstructured":"WHO review of malaria vaccine clinical development. https:\/\/www.who.int\/observatories\/global-observatory-on-health-research-and-development\/monitoring\/who-review-of-malaria-vaccine-clinical-development (2025)."},{"key":"1455_CR5","doi-asserted-by":"publisher","first-page":"1576","DOI":"10.1093\/infdis\/171.6.1576","volume":"171","author":"DM Gordon","year":"1995","unstructured":"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\u20131585 (1995).","journal-title":"J. Infect. Dis."},{"key":"1455_CR6","doi-asserted-by":"publisher","DOI":"10.1038\/srep46621","volume":"7","author":"KA Collins","year":"2017","unstructured":"Collins, K. A., Snaith, R., Cottingham, M. G., Gilbert, S. C. & Hill, A. V. S. Enhancing protective immunity to malaria with a highly immunogenic virus-like particle vaccine. Sci. Rep. 7, 46621 (2017).","journal-title":"Sci. Rep."},{"key":"1455_CR7","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/S0140-6736(15)60721-8","volume":"386","author":"SCTP Rts","year":"2015","unstructured":"Rts, S. C. T. P. Efficacy and safety of RTS,S\/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial. Lancet 386, 31\u201345 (2015).","journal-title":"Lancet"},{"key":"1455_CR8","unstructured":"Organization, W. H. Life-saving malaria vaccines reach children in 17 endemic countries in 2024. https:\/\/www.who.int\/news-room\/feature-stories\/detail\/life-saving-malaria-vaccines-reach-children-in-17-endemic-countries-in-2024 (2024)."},{"key":"1455_CR9","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1016\/S0140-6736(23)02511-4","volume":"403","author":"MS Datoo","year":"2024","unstructured":"Datoo, M. S. et al. Safety and efficacy of malaria vaccine candidate R21\/Matrix-M in African children: a multicentre, double-blind, randomised, phase 3 trial. Lancet 403, 533\u2013544 (2024).","journal-title":"Lancet"},{"key":"1455_CR10","doi-asserted-by":"publisher","first-page":"1728","DOI":"10.1016\/S1473-3099(22)00442-X","volume":"22","author":"MS Datoo","year":"2022","unstructured":"Datoo, M. S. et al. Efficacy and immunogenicity of R21\/Matrix-M vaccine against clinical malaria after 2 years\u2019 follow-up in children in Burkina Faso: a phase 1\/2b randomised controlled trial. Lancet Infect. Dis. 22, 1728\u20131736 (2022).","journal-title":"Lancet Infect. Dis."},{"key":"1455_CR11","doi-asserted-by":"publisher","first-page":"1809","DOI":"10.1016\/S0140-6736(21)00943-0","volume":"397","author":"MS Datoo","year":"2021","unstructured":"Datoo, M. S. et al. Efficacy of a low-dose candidate malaria vaccine, R21 in adjuvant Matrix-M, with seasonal administration to children in Burkina Faso: a randomised controlled trial. Lancet 397, 1809\u20131818 (2021).","journal-title":"Lancet"},{"key":"1455_CR12","doi-asserted-by":"publisher","first-page":"1450","DOI":"10.1016\/S1473-3099(15)00239-X","volume":"15","author":"MT White","year":"2015","unstructured":"White, M. T. et al. Immunogenicity of the RTS,S\/AS01 malaria vaccine and implications for duration of vaccine efficacy: secondary analysis of data from a phase 3 randomised controlled trial. Lancet Infect. Dis. 15, 1450\u20131458 (2015).","journal-title":"Lancet Infect. Dis."},{"key":"1455_CR13","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-014-0117-2","volume":"12","author":"MT White","year":"2014","unstructured":"White, M. T. et al. A combined analysis of immunogenicity, antibody kinetics and vaccine efficacy from phase 2 trials of the RTS,S malaria vaccine. BMC Med. 12, 117 (2014).","journal-title":"BMC Med."},{"key":"1455_CR14","doi-asserted-by":"publisher","unstructured":"Minsoko, P. A. et al. Efficacy and safety of the RTS,S\/AS01 malaria vaccine during 18 months after vaccination: a phase 3 randomized, controlled trial in children and young infants at 11 African sites. PLoS Med. 11, https:\/\/doi.org\/10.1371\/journal.pmed.1001685 (2014).","DOI":"10.1371\/journal.pmed.1001685"},{"key":"1455_CR15","doi-asserted-by":"publisher","first-page":"1833","DOI":"10.1056\/NEJMoa2206966","volume":"387","author":"K Kayentao","year":"2022","unstructured":"Kayentao, K. et al. Safety and efficacy of a monoclonal antibody against malaria in Mali. N. Engl. J. Med. 387, 1833\u20131842 (2022).","journal-title":"N. Engl. J. Med."},{"key":"1455_CR16","doi-asserted-by":"publisher","first-page":"1549","DOI":"10.1056\/NEJMoa2312775","volume":"390","author":"K Kayentao","year":"2024","unstructured":"Kayentao, K. et al. Subcutaneous administration of a monoclonal antibody to prevent malaria. N. Engl. J. Med. 390, 1549\u20131559 (2024).","journal-title":"N. Engl. J. Med."},{"key":"1455_CR17","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.csbj.2015.11.001","volume":"14","author":"J Lopez-Sagaseta","year":"2016","unstructured":"Lopez-Sagaseta, J., Malito, E., Rappuoli, R. & Bottomley, M. J. Self-assembling protein nanoparticles in the design of vaccines. Comput. Struct. Biotechnol. J. 14, 58\u201368 (2016).","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"1455_CR18","doi-asserted-by":"publisher","unstructured":"Morales-Hernandez, S., Ugidos-Damboriena, N. & Lopez-Sagaseta, J. Self-assembling protein nanoparticles in the design of vaccines: 2022 update. Vaccines 10, https:\/\/doi.org\/10.3390\/vaccines10091447 (2022).","DOI":"10.3390\/vaccines10091447"},{"key":"1455_CR19","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adf3309","volume":"15","author":"KW Cohen","year":"2023","unstructured":"Cohen, K. W. et al. A first-in-human germline-targeting HIV nanoparticle vaccine induced broad and publicly targeted helper T cell responses. Sci. Transl. Med. 15, eadf3309 (2023).","journal-title":"Sci. Transl. Med."},{"key":"1455_CR20","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-024-00959-0","volume":"9","author":"JP Casazza","year":"2024","unstructured":"Casazza, J. P. et al. Phase 1 dose-escalation trial evaluating a group 2 influenza hemagglutinin stabilized stem nanoparticle vaccine. NPJ Vaccines 9, 171 (2024).","journal-title":"NPJ Vaccines"},{"key":"1455_CR21","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.ade4790","volume":"15","author":"AT Widge","year":"2023","unstructured":"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).","journal-title":"Sci. Transl. Med."},{"key":"1455_CR22","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.110143","volume":"37","author":"MG Joyce","year":"2021","unstructured":"Joyce, M. G. et al. SARS-CoV-2 ferritin nanoparticle vaccines elicit broad SARS coronavirus immunogenicity. Cell Rep. 37, 110143 (2021).","journal-title":"Cell Rep."},{"key":"1455_CR23","doi-asserted-by":"publisher","first-page":"e581","DOI":"10.1016\/S2666-5247(23)00410-X","volume":"5","author":"BL Ober Shepherd","year":"2024","unstructured":"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\u2013e593 (2024).","journal-title":"Lancet Microbe"},{"key":"1455_CR24","doi-asserted-by":"publisher","unstructured":"Swanson, K. A. et al. A respiratory syncytial virus (RSV) F protein nanoparticle vaccine focuses antibody responses to a conserved neutralization domain. Sci. Immunol. 5, https:\/\/doi.org\/10.1126\/sciimmunol.aba6466 (2020).","DOI":"10.1126\/sciimmunol.aba6466"},{"key":"1455_CR25","doi-asserted-by":"publisher","first-page":"763","DOI":"10.2217\/fvl-2020-0174","volume":"15","author":"LM Stephens","year":"2020","unstructured":"Stephens, L. M. & Varga, S. M. Nanoparticle vaccines against respiratory syncytial virus. Future Virol. 15, 763\u2013778 (2020).","journal-title":"Future Virol."},{"key":"1455_CR26","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-020-00274-4","volume":"6","author":"L Jelinkova","year":"2021","unstructured":"Jelinkova, L. et al. An epitope-based malaria vaccine targeting the junctional region of circumsporozoite protein. NPJ Vaccines 6, 13 (2021).","journal-title":"NPJ Vaccines"},{"key":"1455_CR27","doi-asserted-by":"publisher","unstructured":"Francica, J. R. et al. Design of alphavirus virus-like particles presenting circumsporozoite junctional epitopes that elicit protection against malaria. Vaccines 9, https:\/\/doi.org\/10.3390\/vaccines9030272 (2021).","DOI":"10.3390\/vaccines9030272"},{"key":"1455_CR28","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-022-00457-1","volume":"7","author":"L Jelinkova","year":"2022","unstructured":"Jelinkova, L. et al. A vaccine targeting the L9 epitope of the malaria circumsporozoite protein confers protection from blood-stage infection in a mouse challenge model. NPJ Vaccines 7, 34 (2022).","journal-title":"NPJ Vaccines"},{"key":"1455_CR29","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-025-01241-7","volume":"10","author":"Y Nepal","year":"2025","unstructured":"Nepal, Y. et al. Virus-like particle vaccines targeting a key epitope in circumsporozoite protein provide sterilizing immunity against malaria. NPJ Vaccines 10, 176 (2025).","journal-title":"NPJ Vaccines"},{"key":"1455_CR30","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-023-00653-7","volume":"8","author":"J Ludwig","year":"2023","unstructured":"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).","journal-title":"NPJ Vaccines"},{"key":"1455_CR31","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-025-01140-x","volume":"10","author":"MD Langowski","year":"2025","unstructured":"Langowski, M. D. et al. Elicitation of liver-stage immunity by nanoparticle immunogens displaying P. falciparum CSP-derived antigens. NPJ Vaccines 10, 87 (2025).","journal-title":"NPJ Vaccines"},{"key":"1455_CR32","doi-asserted-by":"publisher","unstructured":"Sun, Z. W. et al. An immunogen containing four tandem 10E8 epitope repeats with exposed key residues induces antibodies that neutralize HIV-1 and activates an ADCC reporter gene. Emerg. Microbes Infect. 5, https:\/\/doi.org\/10.1038\/emi.2016.86 (2016).","DOI":"10.1038\/emi.2016.86"},{"key":"1455_CR33","doi-asserted-by":"publisher","first-page":"10722","DOI":"10.1021\/acsnano.1c04078","volume":"15","author":"S Kang","year":"2021","unstructured":"Kang, S., Kim, Y., Shin, Y., Song, J. J. & Jon, S. Antigen-presenting, self-assembled protein nanobarrels as an adjuvant-free vaccine platform against influenza virus. ACS Nano 15, 10722\u201310732 (2021).","journal-title":"ACS Nano"},{"key":"1455_CR34","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1038\/nm.4512","volume":"24","author":"NK Kisalu","year":"2018","unstructured":"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\u2013416 (2018).","journal-title":"Nat. Med."},{"key":"1455_CR35","doi-asserted-by":"publisher","first-page":"2859","DOI":"10.1016\/j.immuni.2021.10.017","volume":"54","author":"S Kratochvil","year":"2021","unstructured":"Kratochvil, S. et al. Vaccination in a humanized mouse model elicits highly protective PfCSP-targeting anti-malarial antibodies. Immunity 54, 2859\u20132876.e2857 (2021).","journal-title":"Immunity"},{"key":"1455_CR36","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2025.112903","volume":"28","author":"M Reveiz","year":"2025","unstructured":"Reveiz, M. et al. In silico improvement of affinity for highly protective anti-malarial antibodies. iScience 28, 112903 (2025).","journal-title":"iScience"},{"key":"1455_CR37","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1016\/j.immuni.2020.08.014","volume":"53","author":"LT Wang","year":"2020","unstructured":"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\u2013744.e738 (2020).","journal-title":"Immunity"},{"key":"1455_CR38","doi-asserted-by":"publisher","first-page":"E10438","DOI":"10.1073\/pnas.1715812114","volume":"114","author":"D Oyen","year":"2017","unstructured":"Oyen, D. et al. Structural basis for antibody recognition of the NANP repeats in Plasmodium falciparum circumsporozoite protein. Proc. Natl. Acad. Sci. USA 114, E10438\u2013E10445 (2017).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"1455_CR39","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-90290-8","volume":"11","author":"KA Collins","year":"2021","unstructured":"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).","journal-title":"Sci. Rep."},{"key":"1455_CR40","doi-asserted-by":"publisher","first-page":"27","DOI":"10.4103\/0976-0105.177703","volume":"7","author":"AB Nair","year":"2016","unstructured":"Nair, A. B. & Jacob, S. A simple practice guide for dose conversion between animals and human. J. Basic Clin. Pharm. 7, 27\u201331 (2016).","journal-title":"J. Basic Clin. Pharm."},{"key":"1455_CR41","doi-asserted-by":"publisher","first-page":"2555","DOI":"10.1002\/j.1460-2075.1988.tb03104.x","volume":"7","author":"M Guttinger","year":"1988","unstructured":"Guttinger, M. et al. Human T cells recognize polymorphic and non-polymorphic regions of the Plasmodium falciparum circumsporozoite protein. EMBO J. 7, 2555\u20132558 (1988).","journal-title":"EMBO J."},{"key":"1455_CR42","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1038\/334258a0","volume":"334","author":"S Kumar","year":"1988","unstructured":"Kumar, S. et al. Cytotoxic T cells specific for the circumsporozoite protein of Plasmodium falciparum. Nature 334, 258\u2013260 (1988).","journal-title":"Nature"},{"key":"1455_CR43","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1038\/336778a0","volume":"336","author":"F Sinigaglia","year":"1988","unstructured":"Sinigaglia, F. et al. A malaria T-cell epitope recognized in association with most mouse and human MHC class-II molecules. Nature 336, 778\u2013780 (1988).","journal-title":"Nature"},{"key":"1455_CR44","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1007\/BF02788751","volume":"18","author":"J Alexander","year":"1998","unstructured":"Alexander, J. et al. The optimization of helper T lymphocyte (HTL) function in vaccine development. Immunol. Res. 18, 79\u201392 (1998).","journal-title":"Immunol. Res."},{"key":"1455_CR45","doi-asserted-by":"publisher","first-page":"1038","DOI":"10.1093\/infdis\/jit282","volume":"208","author":"C Rosa","year":"2013","unstructured":"Rosa, C. et al. Clinical evaluation of safety and immunogenicity of PADRE-cytomegalovirus (CMV) and tetanus-CMV fusion peptide vaccines with or without PF03512676 adjuvant (vol 205, pg 1294, 2012). J. Infect. Dis. 208, 1038\u20131038 (2013).","journal-title":"J. Infect. Dis."},{"key":"1455_CR46","doi-asserted-by":"publisher","first-page":"4743","DOI":"10.1073\/pnas.1803457115","volume":"115","author":"P Dosenovic","year":"2018","unstructured":"Dosenovic, P. et al. Anti-HIV-1 B cell responses are dependent on B cell precursor frequency and antigen-binding affinity. Proc. Natl. Acad. Sci. USA 115, 4743\u20134748 (2018).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"1455_CR47","doi-asserted-by":"publisher","unstructured":"McDaniel, J. R. et al. Repertoire, function, and structure of serological antibodies induced by the R21\/Matrix-M malaria vaccine. J. Exp. Med. 222, https:\/\/doi.org\/10.1084\/jem.20241908 (2025).","DOI":"10.1084\/jem.20241908"},{"key":"1455_CR48","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.1038\/s41591-020-0881-9","volume":"26","author":"R Murugan","year":"2020","unstructured":"Murugan, R. et al. Evolution of protective human antibodies against Plasmodium falciparum circumsporozoite protein repeat motifs. Nat. Med. 26, 1135\u20131145 (2020).","journal-title":"Nat. Med."},{"key":"1455_CR49","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1038\/s41591-023-02659-z","volume":"30","author":"KL Williams","year":"2024","unstructured":"Williams, K. L. et al. A candidate antibody drug for prevention of malaria. Nat. Med. 30, 117\u2013129 (2024).","journal-title":"Nat. Med."},{"key":"1455_CR50","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.113330","volume":"42","author":"E Thai","year":"2023","unstructured":"Thai, E. et al. Molecular determinants of cross-reactivity and potency by VH3-33 antibodies against the Plasmodium falciparum circumsporozoite protein. Cell Rep. 42, 113330 (2023).","journal-title":"Cell Rep."},{"key":"1455_CR51","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1016\/j.cell.2010.10.032","volume":"143","author":"GD Victora","year":"2010","unstructured":"Victora, G. D. et al. Germinal center dynamics revealed by multiphoton microscopy with a photoactivatable fluorescent reporter. Cell 143, 592\u2013605 (2010).","journal-title":"Cell"},{"key":"1455_CR52","doi-asserted-by":"publisher","DOI":"10.1126\/science.abn8934","volume":"379","author":"A Aung","year":"2023","unstructured":"Aung, A. et al. Low protease activity in B cell follicles promotes retention of intact antigens after immunization. Science 379, eabn8934 (2023).","journal-title":"Science"},{"key":"1455_CR53","doi-asserted-by":"publisher","first-page":"e1010042","DOI":"10.1371\/journal.ppat.1010042","volume":"17","author":"Y Flores-Garcia","year":"2021","unstructured":"Flores-Garcia, Y. et al. The P. falciparum CSP repeat region contains three distinct epitopes required for protection by antibodies in vivo. PLoS Pathog. 17, e1010042 (2021).","journal-title":"PLoS Pathog."},{"key":"1455_CR54","doi-asserted-by":"crossref","unstructured":"Mastronarde DN. Automated electron microscope tomography using robust prediction of specimen movements. J Struct. Biol. 152, 36\u201351 (2005).","DOI":"10.1016\/j.jsb.2005.07.007"},{"key":"1455_CR55","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-35456-2","volume":"13","author":"NS Lima","year":"2022","unstructured":"Lima, N. S. et al. Primary exposure to SARS-CoV-2 variants elicits convergent epitope specificities, immunoglobulin V gene usage and public B cell clones. Nat. Commun. 13, 7733 (2022).","journal-title":"Nat. Commun."}],"container-title":["npj Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41541-026-01455-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41541-026-01455-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41541-026-01455-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T01:08:47Z","timestamp":1782954527000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41541-026-01455-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,27]]},"references-count":55,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1455"],"URL":"https:\/\/doi.org\/10.1038\/s41541-026-01455-3","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2025.09.05.665822","asserted-by":"object"}]},"ISSN":["2059-0105"],"issn-type":[{"value":"2059-0105","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,27]]},"assertion":[{"value":"1 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 April 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The NIH has submitted on behalf of R.A.S., P.D.K., P.T., and B.Z. a US Provisional Patent Application E-237-2024-0-US-01, filed on April 16th, 2025, describing the nanoparticle immunogens and their use. All other authors declare no competing interests. F.D.B. has consultancy relationships with Adimab, Third Rock Ventures, and The EMBO Journal and founded BliNK Therapeutics.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"133"}}