{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:14:31Z","timestamp":1787030071831,"version":"build-2736575974"},"reference-count":52,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T00:00:00Z","timestamp":1616025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016820","name":"Vaccine Research Center","doi-asserted-by":"publisher","award":["ZIA AI005024-19"],"award-info":[{"award-number":["ZIA AI005024-19"]}],"id":[{"id":"10.13039\/100016820","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>The most advanced malaria vaccine, RTS,S, includes the central repeat and C-terminal domains of the Plasmodium falciparum circumsporozoite protein (PfCSP). We have recently isolated human antibodies that target the junctional region between the N-terminal and repeat domains that are not included in RTS,S. Due to the fact that these antibodies protect against malaria challenge in mice, their epitopes could be effective vaccine targets. Here, we developed immunogens displaying PfCSP junctional epitopes by genetic fusion to either the N-terminus or B domain loop of the E2 protein from chikungunya (CHIK) alphavirus and produced CHIK virus-like particles (CHIK-VLPs). The structural integrity of these junctional-epitope\u2013CHIK-VLP immunogens was confirmed by negative-stain electron microscopy. Immunization of these CHIK-VLP immunogens reduced parasite liver load by up to 95% in a mouse model of malaria infection and elicited better protection than when displayed on keyhole limpet hemocyanin, a commonly used immunogenic carrier. Protection correlated with PfCSP serum titer. Of note, different junctional sequences elicited qualitatively different reactivities to overlapping PfCSP peptides. Overall, these results show that the junctional epitopes of PfCSP can induce protective responses when displayed on CHIK-VLP immunogens and provide a basis for the development of a next generation malaria vaccine to expand the breadth of anti-PfCSP immunity.<\/jats:p>","DOI":"10.3390\/vaccines9030272","type":"journal-article","created":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T22:19:36Z","timestamp":1616105976000},"page":"272","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Design of Alphavirus Virus-Like Particles Presenting Circumsporozoite Junctional Epitopes That Elicit Protection against Malaria"],"prefix":"10.3390","volume":"9","author":[{"given":"Joseph R.","family":"Francica","sequence":"first","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Shi","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwo-Yu","family":"Chuang","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven J.","family":"Chen","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lais","family":"Da Silva Pereira","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8785-8039","authenticated-orcid":false,"given":"S. Katie","family":"Farney","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara J.","family":"Flynn","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5653-8684","authenticated-orcid":false,"given":"Li","family":"Ou","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler","family":"Stephens","sequence":"additional","affiliation":[{"name":"Electron Microscopy Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research Sponsored by the National Cancer Institute, Frederick, MD 21701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaroslav","family":"Tsybovsky","sequence":"additional","affiliation":[{"name":"Electron Microscopy Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research Sponsored by the National Cancer Institute, Frederick, MD 21701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence T.","family":"Wang","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Anderson","sequence":"additional","affiliation":[{"name":"Laboratory of Adjuvant &amp; Antigen Research, US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoltan","family":"Beck","sequence":"additional","affiliation":[{"name":"Laboratory of Adjuvant &amp; Antigen Research, US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlon","family":"Dillon","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1847-5488","authenticated-orcid":false,"given":"Azza H.","family":"Idris","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9891-916X","authenticated-orcid":false,"given":"Nicholas","family":"Hurlburt","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy","family":"Liu","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baoshan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1913-3909","authenticated-orcid":false,"given":"Carl R.","family":"Alving","sequence":"additional","affiliation":[{"name":"Laboratory of Adjuvant &amp; Antigen Research, US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary R.","family":"Matyas","sequence":"additional","affiliation":[{"name":"Laboratory of Adjuvant &amp; Antigen Research, US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Pancera","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA"},{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Mascola","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3560-232X","authenticated-orcid":false,"given":"Peter D.","family":"Kwong","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Seder","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,18]]},"reference":[{"key":"ref_1","unstructured":"WHO (2020, November 24). Malaria. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/malaria."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1038\/nature03342","article-title":"The global distribution of clinical episodes of Plasmodium falciparum malaria","volume":"434","author":"Snow","year":"2005","journal-title":"Nature"},{"key":"ref_3","unstructured":"Programme, G.M. (2019). World Malria Report, World Health Organization."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Ciss\u00e9, B., Ba, E.H., Sokhna, C., NDiaye, J.L., Gomis, J.F., Dial, Y., Pitt, C., Ndiaye, M., Cairns, M., and Faye, E. (2016). Effectiveness of Seasonal Malaria Chemoprevention in Children under Ten Years of Age in Senegal: A Stepped-Wedge Cluster-Randomised Trial. PLoS Med., 13.","DOI":"10.1371\/journal.pmed.1002175"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1111\/j.1365-3156.2009.02287.x","article-title":"From malaria control to eradication: The WHO perspective","volume":"14","author":"Mendis","year":"2009","journal-title":"Trop. Med. Int. Health"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Strode, C., Donegan, S., Garner, P., Enayati, A.A., and Hemingway, J. (2014). The impact of pyrethroid resistance on the efficacy of insecticide-treated bed nets against African anopheline mosquitoes: Systematic review and meta-analysis. PLoS Med., 11.","DOI":"10.1371\/journal.pmed.1001619"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1038\/s41590-018-0228-6","article-title":"Malaria prevention: From immunological concepts to effective vaccines and protective antibodies","volume":"19","author":"Cockburn","year":"2018","journal-title":"Nat. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"46621","DOI":"10.1038\/srep46621","article-title":"Enhancing protective immunity to malaria with a highly immunogenic virus-like particle vaccine","volume":"7","author":"Collins","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1126\/science.1241800","article-title":"Protection against malaria by intravenous immunization with a nonreplicating sporozoite vaccine","volume":"341","author":"Seder","year":"2013","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Schwenk, R., DeBot, M., Porter, M., Nikki, J., Rein, L., Spaccapelo, R., Crisanti, A., Wightman, P.D., Ockenhouse, C.F., and Dutta, S. (2014). IgG2 antibodies against a clinical grade Plasmodium falciparum CSP vaccine antigen associate with protection against transgenic sporozoite challenge in mice. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0111020"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.3389\/fimmu.2019.01254","article-title":"Functional Comparison of Blood-Stage Plasmodium falciparum Malaria Vaccine Candidate Antigens","volume":"10","author":"Illingworth","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e96381","DOI":"10.1172\/jci.insight.96381","article-title":"Human vaccination against RH5 induces neutralizing antimalarial antibodies that inhibit RH5 invasion complex interactions","volume":"2","author":"Payne","year":"2017","journal-title":"JCI Insight"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1038\/nbt0594-494","article-title":"Production, purification and immunogenicity of a malaria transmission-blocking vaccine candidate: TBV25H expressed in yeast and purified using nickel-NTA agarose","volume":"12","author":"Kaslow","year":"1994","journal-title":"Biotechnology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2954","DOI":"10.1016\/j.vaccine.2013.04.034","article-title":"Development of a Pfs25-EPA malaria transmission blocking vaccine as a chemically conjugated nanoparticle","volume":"31","author":"Shimp","year":"2013","journal-title":"Vaccine"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"696","DOI":"10.4103\/0971-5916.191927","article-title":"Strategies & recent development of transmission-blocking vaccines against Plasmodium falciparum","volume":"143","author":"Chaturvedi","year":"2016","journal-title":"Indian J. Med. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e89154","DOI":"10.1172\/jci.insight.89154","article-title":"Protection against Plasmodium falciparum malaria by PfSPZ Vaccine","volume":"2","author":"Epstein","year":"2017","journal-title":"JCI Insight"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/S1473-3099(17)30104-4","article-title":"Safety and efficacy of PfSPZ Vaccine against Plasmodium falciparum via direct venous inoculation in healthy malaria-exposed adults in Mali: A randomised, double-blind phase 1 trial","volume":"17","author":"Sissoko","year":"2017","journal-title":"Lancet Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"338","DOI":"10.4269\/ajtmh.17-1014","article-title":"Safety, Immunogenicity, and Protective Efficacy against Controlled Human Malaria Infection of Plasmodium falciparum Sporozoite Vaccine in Tanzanian Adults","volume":"99","author":"Jongo","year":"2018","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1093\/infdis\/171.6.1576","article-title":"Safety, immunogenicity, and efficacy of a recombinantly produced Plasmodium falciparum circumsporozoite protein-hepatitis B surface antigen subunit vaccine","volume":"171","author":"Gordon","year":"1995","journal-title":"J. Infect. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1586\/erv.11.29","article-title":"Recent clinical experience with vaccines using MPL- and QS-21-containing adjuvant systems","volume":"10","author":"Garcon","year":"2011","journal-title":"Expert Rev. Vaccines"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0140-6736(15)60721-8","article-title":"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","volume":"386","author":"Rts","year":"2015","journal-title":"Lancet"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.1056\/NEJMoa1102287","article-title":"First results of phase 3 trial of RTS,S\/AS01 malaria vaccine in African children","volume":"365","author":"Rts","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"White, M.T., Bejon, P., Olotu, A., Griffin, J.T., Riley, E.M., Kester, K.E., Ockenhouse, C.F., and Ghani, A.C. (2013). The relationship between RTS,S vaccine-induced antibodies, CD4(+) T cell responses and protection against Plasmodium falciparum infection. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0061395"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"White, M.T., Bejon, P., Olotu, A., Griffin, J.T., Bojang, K., Lusingu, J., Salim, N., Abdulla, S., Otsyula, N., and Agnandji, S.T. (2014). A combined analysis of immunogenicity, antibody kinetics and vaccine efficacy from phase 2 trials of the RTS,S malaria vaccine. BMC Med., 12.","DOI":"10.1186\/s12916-014-0117-2"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1016\/S1473-3099(15)00239-X","article-title":"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","volume":"15","author":"White","year":"2015","journal-title":"Lancet Infect. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"E10438","DOI":"10.1073\/pnas.1715812114","article-title":"Structural basis for antibody recognition of the NANP repeats in Plasmodium falciparum circumsporozoite protein","volume":"114","author":"Oyen","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2174","DOI":"10.1038\/s41467-019-10195-z","article-title":"Concentration and avidity of antibodies to different circumsporozoite epitopes correlate with RTS,S\/AS01E malaria vaccine efficacy","volume":"10","author":"Dobano","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1186\/s12936-016-1348-9","article-title":"The biological function of antibodies induced by the RTS,S\/AS01 malaria vaccine candidate is determined by their fine specificity","volume":"15","author":"Chaudhury","year":"2016","journal-title":"Malar. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1093\/infdis\/jiw237","article-title":"Fractional Third and Fourth Dose of RTS,S\/AS01 Malaria Candidate Vaccine: A Phase 2a Controlled Human Malaria Parasite Infection and Immunogenicity Study","volume":"214","author":"Regules","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"7498","DOI":"10.1016\/j.vaccine.2020.09.069","article-title":"Modelling the roles of antibody titre and avidity in protection from Plasmodium falciparum malaria infection following RTS,S\/AS01 vaccination","volume":"38","author":"Thompson","year":"2020","journal-title":"Vaccine"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1038\/nm.4512","article-title":"A human monoclonal antibody prevents malaria infection by targeting a new site of vulnerability on the parasite","volume":"24","author":"Kisalu","year":"2018","journal-title":"Nat. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/nm.4513","article-title":"A public antibody lineage that potently inhibits malaria infection through dual binding to the circumsporozoite protein","volume":"24","author":"Tan","year":"2018","journal-title":"Nat. Med."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Oyen, D., Torres, J.L., Aoto, P.C., Flores-Garcia, Y., Binter, S., Pholcharee, T., Carroll, S., Reponen, S., Wash, R., and Liang, Q. (2020). Structure and mechanism of monoclonal antibody binding to the junctional epitope of Plasmodium falciparum circumsporozoite protein. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008373"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/j.immuni.2020.08.014","article-title":"A Potent Anti-Malarial Human Monoclonal Antibody Targets Circumsporozoite Protein Minor Repeats and Neutralizes Sporozoites in the Liver","volume":"53","author":"Wang","year":"2020","journal-title":"Immunity"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1038\/s41591-018-0042-6","article-title":"Epitope-based vaccine design yields fusion peptide-directed antibodies that neutralize diverse strains of HIV-1","volume":"24","author":"Xu","year":"2018","journal-title":"Nat. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/j.cell.2019.06.030","article-title":"Antibody Lineages with Vaccine-Induced Antigen-Binding Hotspots Develop Broad HIV Neutralization","volume":"178","author":"Kong","year":"2019","journal-title":"Cell"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Cheng, C., Xu, K., Kong, R., Chuang, G.Y., Corrigan, A.R., Geng, H., Hill, K.R., Jafari, A.J., O\u2019Dell, S., and Ou, L. (2019). Consistent elicitation of cross-clade HIV-neutralizing responses achieved in guinea pigs after fusion peptide priming by repetitive envelope trimer boosting. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0215163"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Chuang, G.Y., Lai, Y.T., Boyington, J.C., Cheng, C., Geng, H., Narpala, S., Rawi, R., Schmidt, S.D., Tsybovsky, Y., and Verardi, R. (2020). Development of a 3Mut-Apex-Stabilized Envelope Trimer That Expands HIV-1 Neutralization Breadth When Used To Boost Fusion Peptide-Directed Vaccine-Elicited Responses. J. Virol., 94.","DOI":"10.1128\/JVI.00074-20"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1038\/nm.2105","article-title":"A virus-like particle vaccine for epidemic Chikungunya virus protects nonhuman primates against infection","volume":"16","author":"Akahata","year":"2010","journal-title":"Nat. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1001\/jama.2020.2477","article-title":"Effect of a Chikungunya Virus-Like Particle Vaccine on Safety and Tolerability Outcomes: A Randomized Clinical Trial","volume":"323","author":"Chen","year":"2020","journal-title":"JAMA"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Urakami, A., Sakurai, A., Ishikawa, M., Yap, M.L., Flores-Garcia, Y., Haseda, Y., Aoshi, T., Zavala, F.P., Rossmann, M.G., and Kuno, S. (2017). Development of a Novel Virus-Like Particle Vaccine Platform That Mimics the Immature Form of Alphavirus. Clin. Vaccine Immunol., 24.","DOI":"10.1128\/CVI.00090-17"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.jsb.2006.05.009","article-title":"EMAN2: An extensible image processing suite for electron microscopy","volume":"157","author":"Tang","year":"2007","journal-title":"J. Struct. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1080\/14760584.2020.1745636","article-title":"Army Liposome Formulation (ALF) family of vaccine adjuvants","volume":"19","author":"Alving","year":"2020","journal-title":"Expert Rev. Vaccines"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1186\/s12936-019-3055-9","article-title":"Optimization of an in vivo model to study immunity to Plasmodium falciparum pre-erythrocytic stages","volume":"18","author":"Herrera","year":"2019","journal-title":"Malar. J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1038\/nature09555","article-title":"Glycoprotein organization of Chikungunya virus particles revealed by X-ray crystallography","volume":"468","author":"Voss","year":"2010","journal-title":"Nature"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3793","DOI":"10.1016\/j.vaccine.2019.05.059","article-title":"Safety, toxicity and immunogenicity of a malaria vaccine based on the circumsporozoite protein (FMP013) with the adjuvant army liposome formulation containing QS21 (ALFQ)","volume":"37","author":"Cawlfield","year":"2019","journal-title":"Vaccine"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3865","DOI":"10.1016\/j.vaccine.2017.05.070","article-title":"Liposomes containing monophosphoryl lipid A and QS-21 serve as an effective adjuvant for soluble circumsporozoite protein malaria vaccine FMP013","volume":"35","author":"Genito","year":"2017","journal-title":"Vaccine"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/s41541-020-00274-4","article-title":"An epitope-based malaria vaccine targeting the junctional region of circumsporozoite protein","volume":"6","author":"Jelinkova","year":"2021","journal-title":"NPJ Vaccines"},{"key":"ref_49","first-page":"1","article-title":"Identification of a neutralizing epitope within minor repeat region of Plasmodium falciparum CS protein","volume":"6","author":"Mitchell","year":"2021","journal-title":"NPJ Vaccines"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1038\/s41591-020-0881-9","article-title":"Evolution of protective human antibodies against Plasmodium falciparum circumsporozoite protein repeat motifs","volume":"26","author":"Murugan","year":"2020","journal-title":"Nat. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1016\/j.jmb.2019.12.029","article-title":"Diverse Antibody Responses to Conserved Structural Motifs in Plasmodium falciparum Circumsporozoite Protein","volume":"432","author":"Pholcharee","year":"2020","journal-title":"J. Mol. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3114","DOI":"10.1073\/pnas.1911792117","article-title":"Optimization of a Plasmodium falciparum circumsporozoite protein repeat vaccine using the tobacco mosaic virus platform","volume":"117","author":"Langowski","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/9\/3\/272\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:37:30Z","timestamp":1760161050000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/9\/3\/272"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,18]]},"references-count":52,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["vaccines9030272"],"URL":"https:\/\/doi.org\/10.3390\/vaccines9030272","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,18]]}}}