{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T21:16:34Z","timestamp":1789766194749,"version":"4.0.1"},"reference-count":86,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T00:00:00Z","timestamp":1663286400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Recombinant protein-based vaccines are a valid and safer alternative to traditional vaccines based on live-attenuated or killed pathogens. However, the immune response of subunit vaccines is generally lower compared to that elicited by traditional vaccines and usually requires the use of adjuvants. The use of self-assembling protein nanoparticles, as a platform for vaccine antigen presentation, is emerging as a promising approach to enhance the production of protective and functional antibodies. In this work we demonstrated the successful repetitive antigen display of the C-terminal \u03b2-barrel domain of factor H binding protein, derived from serogroup B Meningococcus on the surface of different self-assembling nanoparticles using genetic fusion. Six nanoparticle scaffolds were tested, including virus-like particles with different sizes, geometries, and physicochemical properties. Combining computational and structure-based rational design we were able generate antigen-fused scaffolds that closely aligned with three-dimensional structure predictions. The chimeric nanoparticles were produced as recombinant proteins in <jats:italic>Escherichia coli<\/jats:italic> and evaluated for solubility, stability, self-assembly, and antigen accessibility using a variety of biophysical methods. Several scaffolds were identified as being suitable for genetic fusion with the \u03b2-barrel from fHbp, including ferritin, a <jats:italic>de novo<\/jats:italic> designed aldolase from <jats:italic>Thermotoga maritima<\/jats:italic>, encapsulin, CP3 phage coat protein, and the Hepatitis B core antigen. In conclusion, a systematic screening of self-assembling nanoparticles has been applied for the repetitive surface display of a vaccine antigen. This work demonstrates the capacity of rational structure-based design to develop new chimeric nanoparticles and describes a strategy that can be utilized to discover new nanoparticle-based approaches in the search for vaccines against bacterial pathogens.<\/jats:p>","DOI":"10.1371\/journal.pone.0273322","type":"journal-article","created":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T17:35:31Z","timestamp":1663349731000},"page":"e0273322","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":27,"title":["Self-assembling protein nanoparticles and virus like particles correctly display \u03b2-barrel from meningococcal factor H-binding protein through genetic fusion"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3991-3611","authenticated-orcid":true,"given":"Luigia","family":"Cappelli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Cinelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiola","family":"Giusti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Ferlenghi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Utrio-Lanfaloni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Newton","family":"Wahome","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9734-5694","authenticated-orcid":true,"given":"Matthew James","family":"Bottomley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Maione","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7774-6167","authenticated-orcid":true,"given":"Roberta","family":"Cozzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,9,16]]},"reference":[{"key":"pone.0273322.ref001","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.csbj.2015.11.001","article-title":"Self-assembling protein nanoparticles in the design of vaccines","volume":"14","author":"J. Lopez-Sagaseta","year":"2016","journal-title":"Comput Struct Biotechnol J"},{"issue":"2","key":"pone.0273322.ref002","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1111\/mmi.13117","article-title":"Bacterial microcompartments: widespread prokaryotic organelles for isolation and optimization of metabolic pathways","volume":"98","author":"T.A. Bobik","year":"2015","journal-title":"Mol Microbiol"},{"issue":"6","key":"pone.0273322.ref003","doi-asserted-by":"crossref","DOI":"10.1038\/nmicrobiol.2017.29","article-title":"Widespread distribution of encapsulin nanocompartments reveals functional diversity","volume":"2","author":"T.W. Giessen","year":"2017","journal-title":"Nature Microbiology"},{"key":"pone.0273322.ref004","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/978-94-007-6552-8_2","article-title":"The basic architecture of viruses","volume":"68","author":"J.R. Caston","year":"2013","journal-title":"Subcell Biochem"},{"issue":"80","key":"pone.0273322.ref005","article-title":"Nanoscale assemblies and their biomedical applications","volume":"10","author":"T.A. Doll","year":"2013","journal-title":"J R Soc Interface"},{"issue":"10","key":"pone.0273322.ref006","doi-asserted-by":"crossref","DOI":"10.3390\/pharmaceutics13101621","article-title":"Functionalizing Ferritin Nanoparticles for Vaccine Development","volume":"13","author":"M.Q. Rodrigues","year":"2021","journal-title":"Pharmaceutics"},{"key":"pone.0273322.ref007","volume":"10","author":"S. Al-Halifa","year":"2019","journal-title":"Nanoparticle-Based Vaccines Against Respiratory Viruses"},{"issue":"1","key":"pone.0273322.ref008","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1038\/s41467-020-20251-8","article-title":"Capsid-like particles decorated with the SARS-CoV-2 receptor-binding domain elicit strong virus neutralization activity","volume":"12","author":"C. Fougeroux","year":"2021","journal-title":"Nat Commun"},{"key":"pone.0273322.ref009","article-title":"Efficacy of a Broadly Neutralizing SARS-CoV-2 Ferritin Nanoparticle Vaccine in Nonhuman Primates","author":"M.G. Joyce","year":"2021","journal-title":"bioRxiv"},{"issue":"5","key":"pone.0273322.ref010","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1016\/j.cell.2020.10.043","article-title":"Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2","volume":"183","author":"A.C. Walls","year":"2020","journal-title":"Cell"},{"issue":"1","key":"pone.0273322.ref011","doi-asserted-by":"crossref","first-page":"18149","DOI":"10.1038\/s41598-020-74949-2","article-title":"A platform incorporating trimeric antigens into self-assembling nanoparticles reveals SARS-CoV-2-spike nanoparticles to elicit substantially higher neutralizing responses than spike alone","volume":"10","author":"B. Zhang","year":"2020","journal-title":"Sci Rep"},{"key":"pone.0273322.ref012","unstructured":"Ljubojevi\u0107, S. The human papillomavirus vaccines. (1330-027X (Print))."},{"issue":"10","key":"pone.0273322.ref013","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.1080\/21645515.2016.1184806","article-title":"Hepatitis E virus: Current epidemiology and vaccine","volume":"12","author":"X. Wu","year":"2016","journal-title":"Human vaccines & immunotherapeutics"},{"key":"pone.0273322.ref014","unstructured":"Keating, G.M. and S. Noble. Recombinant hepatitis B vaccine (Engerix-B): a review of its immunogenicity and protective efficacy against hepatitis B. (0012\u20136667 (Print))."},{"issue":"8","key":"pone.0273322.ref015","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1586\/erv.12.70","article-title":"Virus-like particles as universal influenza vaccines","volume":"11","author":"S.-M. Kang","year":"2012","journal-title":"Expert review of vaccines"},{"issue":"13","key":"pone.0273322.ref016","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1056\/NEJMoa2107659","article-title":"Safety and Efficacy of NVX-CoV2373 Covid-19 Vaccine","volume":"385","author":"P.T. Heath","year":"2021","journal-title":"New England Journal of Medicine"},{"issue":"7456","key":"pone.0273322.ref017","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1038\/nature12202","article-title":"Self-assembling influenza nanoparticle vaccines elicit broadly neutralizing H1N1 antibodies","volume":"499","author":"M. Kanekiyo","year":"2013","journal-title":"Nature"},{"issue":"6","key":"pone.0273322.ref018","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1016\/j.cell.2019.01.046","article-title":"Induction of Potent Neutralizing Antibody Responses by a Designed Protein Nanoparticle Vaccine for Respiratory Syncytial Virus","volume":"176","author":"J. Marcandalli","year":"2019","journal-title":"Cell"},{"issue":"2","key":"pone.0273322.ref019","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.cell.2020.02.058","article-title":"Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein","volume":"181","author":"A.C. Walls","year":"2020","journal-title":"Cell"},{"issue":"3","key":"pone.0273322.ref020","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1038\/s41590-018-0305-x","article-title":"Mosaic nanoparticle display of diverse influenza virus hemagglutinins elicits broad B cell responses","volume":"20","author":"M. Kanekiyo","year":"2019","journal-title":"Nature immunology"},{"key":"pone.0273322.ref021","unstructured":"Govasli, M.L., Y. Diaz, and P. Puntervoll. Virus-like particle-display of the enterotoxigenic Escherichia coli heat-stable toxoid STh-A14T elicits neutralizing antibodies in mice. (1873\u20132518 (Electronic))."},{"issue":"16","key":"pone.0273322.ref022","doi-asserted-by":"crossref","first-page":"3201","DOI":"10.1016\/j.vaccine.2020.03.001","article-title":"An assessment of the use of Hepatitis B Virus core protein virus-like particles to display heterologous antigens from Neisseria meningitidis","volume":"38","author":"S. Aston-Deaville","year":"2020","journal-title":"Vaccine"},{"issue":"8","key":"pone.0273322.ref023","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1002\/2211-5463.12267","article-title":"Structure-based design of ferritin nanoparticle immunogens displaying antigenic loops of Neisseria gonorrhoeae","volume":"7","author":"L. Wang","year":"2017","journal-title":"FEBS Open Bio"},{"issue":"3","key":"pone.0273322.ref024","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1016\/j.immuni.2020.08.001","article-title":"Multifaceted Effects of Antigen Valency on B Cell Response Composition and Differentiation In Vivo","volume":"53","author":"Y. Kato","year":"2020","journal-title":"Immunity"},{"issue":"10","key":"pone.0273322.ref025","doi-asserted-by":"crossref","first-page":"3671","DOI":"10.1073\/pnas.73.10.3671","article-title":"Molecular determinants of immunogenicity: the immunon model of immune response","volume":"73","author":"H.M. Dintzis","year":"1976","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"1","key":"pone.0273322.ref026","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/s41541-021-00330-7","article-title":"Protein-based antigen presentation platforms for nanoparticle vaccines","volume":"6","author":"B. Nguyen","year":"2021","journal-title":"NPJ Vaccines"},{"issue":"5","key":"pone.0273322.ref027","doi-asserted-by":"crossref","first-page":"2174","DOI":"10.1021\/cr500399p","article-title":"Advances in Chemical Protein Modification","volume":"115","author":"O. Boutureira","year":"2015","journal-title":"Chemical Reviews"},{"issue":"3","key":"pone.0273322.ref028","doi-asserted-by":"crossref","first-page":"110256","DOI":"10.1016\/j.celrep.2021.110256","article-title":"A bivalent nanoparticle vaccine exhibits potent cross-protection against the variants of SARS-CoV-2","volume":"38","author":"Y. Yuan","year":"2022","journal-title":"Cell Rep"},{"issue":"12","key":"pone.0273322.ref029","doi-asserted-by":"crossref","first-page":"E690","DOI":"10.1073\/pnas.1115485109","article-title":"Peptide tag forming a rapid covalent bond to a protein, through engineering a bacterial adhesin","volume":"109","author":"B. Zakeri","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"pone.0273322.ref030","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.1038\/s41467-019-09678-w","article-title":"Spy&Go purification of SpyTag-proteins using pseudo-SpyCatcher to access an oligomerization toolbox","volume":"10","author":"I.N.A. Khairil Anuar","year":"2019","journal-title":"Nat Commun"},{"issue":"1","key":"pone.0273322.ref031","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.jmb.2009.04.078","article-title":"The crystal structure of ferritin from Helicobacter pylori reveals unusual conformational changes for iron uptake","volume":"390","author":"K.J. Cho","year":"2009","journal-title":"J Mol Biol"},{"issue":"9","key":"pone.0273322.ref032","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1038\/nsmb.1473","article-title":"Structural basis of enzyme encapsulation into a bacterial nanocompartment","volume":"15","author":"M. Sutter","year":"2008","journal-title":"Nat Struct Mol Biol"},{"key":"pone.0273322.ref033","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.nano.2019.01.012","article-title":"Attachment of flagellin enhances the immunostimulatory activity of a hemagglutinin-ferritin nano-cage","volume":"17","author":"E.B. Lee","year":"2019","journal-title":"Nanomedicine"},{"key":"pone.0273322.ref034","doi-asserted-by":"crossref","first-page":"12041","DOI":"10.1038\/ncomms12041","article-title":"Presenting native-like trimeric HIV-1 antigens with self-assembling nanoparticles","volume":"7","author":"L. He","year":"2016","journal-title":"Nat Commun"},{"issue":"7610","key":"pone.0273322.ref035","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1038\/nature18010","article-title":"Design of a hyperstable 60-subunit protein dodecahedron","volume":"535","author":"Y. Hsia","year":"2016","journal-title":"Nature"},{"issue":"9","key":"pone.0273322.ref036","doi-asserted-by":"crossref","first-page":"8855","DOI":"10.1021\/acsnano.8b02805","article-title":"Engineering a Rugged Nanoscaffold To Enhance Plug-and-Display Vaccination","volume":"12","author":"T.U.J. Bruun","year":"2018","journal-title":"ACS Nano"},{"key":"pone.0273322.ref037","doi-asserted-by":"crossref","first-page":"19234","DOI":"10.1038\/srep19234","article-title":"Plug-and-Display: decoration of Virus-Like Particles via isopeptide bonds for modular immunization","volume":"6","author":"K.D. Brune","year":"2016","journal-title":"Sci Rep"},{"issue":"21","key":"pone.0273322.ref038","doi-asserted-by":"crossref","first-page":"4267","DOI":"10.1016\/j.jmb.2016.08.025","article-title":"Structure of AP205 Coat Protein Reveals Circular Permutation in ssRNA Bacteriophages","volume":"428","author":"M. Shishovs","year":"2016","journal-title":"J Mol Biol"},{"issue":"3","key":"pone.0273322.ref039","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.jbiotec.2005.11.013","article-title":"Assembly of bacteriophage Qbeta virus-like particles in yeast Saccharomyces cerevisiae and Pichia pastoris","volume":"123","author":"J. Freivalds","year":"2006","journal-title":"J Biotechnol"},{"issue":"1","key":"pone.0273322.ref040","doi-asserted-by":"crossref","first-page":"3811","DOI":"10.1038\/s41598-017-03798-3","article-title":"Nanoassembly routes stimulate conflicting antibody quantity and quality for transmission-blocking malaria vaccines","volume":"7","author":"D.B. Leneghan","year":"2017","journal-title":"Sci Rep"},{"issue":"1\u20132","key":"pone.0273322.ref041","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1159\/000150469","article-title":"RNA phage Q beta coat protein as a carrier for foreign epitopes","volume":"39","author":"T.M. Kozlovska","year":"1996","journal-title":"Intervirology"},{"issue":"4","key":"pone.0273322.ref042","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1172\/JCI91192","article-title":"T cells control the generation of nanomolar-affinity anti-glycan antibodies","volume":"127","author":"Z. Polonskaya","year":"2017","journal-title":"J Clin Invest"},{"key":"pone.0273322.ref043","doi-asserted-by":"crossref","first-page":"6601","DOI":"10.2147\/IJN.S206210","article-title":"Chimeric hepatitis B virus core particles displaying Neisserial surface protein A confer protection against virulent Neisseria meningitidis serogroup B in BALB\/c mice","volume":"14","author":"Y. Hou","year":"2019","journal-title":"Int J Nanomedicine"},{"key":"pone.0273322.ref044","unstructured":"Maphis, N.M., et al. Q\u00df Virus-like particle-based vaccine induces robust immunity and protects against tauopathy. (2059\u20130105 (Electronic))."},{"issue":"2","key":"pone.0273322.ref045","doi-asserted-by":"crossref","first-page":"e1556","DOI":"10.1371\/journal.pone.0001556","article-title":"Phase I Trial of an Alhydrogel Adjuvanted Hepatitis B Core Virus-Like Particle Containing Epitopes of Plasmodium falciparum Circumsporozoite Protein","volume":"3","author":"A.L. Gregson","year":"2008","journal-title":"PLOS ONE"},{"key":"pone.0273322.ref046","doi-asserted-by":"crossref","first-page":"I46","DOI":"10.1016\/j.vaccine.2008.11.068","article-title":"Factor H-binding protein, a unique meningococcal vaccine antigen","volume":"26","author":"M. Pizza","year":"2008","journal-title":"Vaccine"},{"key":"pone.0273322.ref047","unstructured":"Cantini, F., et al. Solution structure of the factor H-binding protein, a survival factor and protective antigen of Neisseria meningitidis. (0021\u20139258 (Print))."},{"issue":"6","key":"pone.0273322.ref048","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1084\/jem.20021911","article-title":"Vaccination against Neisseria meningitidis using three variants of the lipoprotein GNA1870","volume":"197","author":"V. Masignani","year":"2003","journal-title":"The Journal of experimental medicine"},{"issue":"1","key":"pone.0273322.ref049","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1128\/IAI.01071-08","article-title":"Factor H-binding protein is important for meningococcal survival in human whole blood and serum and in the presence of the antimicrobial peptide LL-37","volume":"77","author":"K.L. Seib","year":"2009","journal-title":"Infect Immun"},{"issue":"11","key":"pone.0273322.ref050","doi-asserted-by":"crossref","first-page":"e0241793","DOI":"10.1371\/journal.pone.0241793","article-title":"Meningococcal B vaccine antigen FHbp variants among disease-causing Neisseria meningitidis B isolates, Italy, 2014\u20132017","volume":"15","author":"A. Carannante","year":"2020","journal-title":"PLoS One"},{"issue":"3","key":"pone.0273322.ref051","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.01231-19","article-title":"A Meningococcal Outer Membrane Vesicle Vaccine with Overexpressed Mutant FHbp Elicits Higher Protective Antibody Responses in Infant Rhesus Macaques than a Licensed Serogroup B Vaccine","volume":"10","author":"P.T. Beernink","year":"2019","journal-title":"mBio"},{"issue":"10","key":"pone.0273322.ref052","doi-asserted-by":"crossref","first-page":"e1002981","DOI":"10.1371\/journal.ppat.1002981","article-title":"Design and evaluation of meningococcal vaccines through structure-based modification of host and pathogen molecules","volume":"8","author":"S. Johnson","year":"2012","journal-title":"PLoS pathogens"},{"issue":"1","key":"pone.0273322.ref053","doi-asserted-by":"crossref","first-page":"3700","DOI":"10.1038\/s41598-018-22057-7","article-title":"Human protective response induced by meningococcus B vaccine is mediated by the synergy of multiple bactericidal epitopes","volume":"8","author":"M. Giuliani","year":"2018","journal-title":"Scientific Reports"},{"issue":"3","key":"pone.0273322.ref054","first-page":"e00842","article-title":"Functional Analysis of the Human Antibody Response to Meningococcal Factor H Binding Protein","volume":"6","author":"T. Beernink Peter","journal-title":"mBio"},{"issue":"11","key":"pone.0273322.ref055","doi-asserted-by":"crossref","first-page":"12099","DOI":"10.1096\/fj.201900374R","article-title":"Cocrystal structure of meningococcal factor H binding protein variant 3 reveals a new crossprotective epitope recognized by human mAb 1E6","volume":"33","author":"F. Bianchi","year":"2019","journal-title":"FASEB journal: official publication of the Federation of American Societies for Experimental Biology"},{"issue":"10","key":"pone.0273322.ref056","doi-asserted-by":"crossref","first-page":"e1008882","DOI":"10.1371\/journal.ppat.1008882","article-title":"4CMenB vaccine induces elite cross-protective human antibodies that compete with human factor H for binding to meningococcal fHbp","volume":"16","author":"D. Veggi","year":"2020","journal-title":"PLoS Pathog"},{"issue":"1","key":"pone.0273322.ref057","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1038\/s41467-018-02827-7","article-title":"Crystal structure reveals vaccine elicited bactericidal human antibody targeting a conserved epitope on meningococcal fHbp","volume":"9","author":"J. L\u00f3pez-Sagaseta","year":"2018","journal-title":"Nature Communications"},{"issue":"10","key":"pone.0273322.ref058","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1016\/j.str.2013.08.005","article-title":"High-resolution comparative modeling with RosettaCM","volume":"21","author":"Y. Song","year":"2013","journal-title":"Structure (London, England: 1993)"},{"issue":"Pt 5","key":"pone.0273322.ref059","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1107\/S1744309111006154","article-title":"Structure of the uncomplexed Neisseria meningitidis factor H-binding protein fHbp (rLP2086)","volume":"67","author":"L. Cendron","year":"2011","journal-title":"Acta crystallographica. Section F, Structural biology and crystallization communications"},{"issue":"8","key":"pone.0273322.ref060","doi-asserted-by":"crossref","first-page":"2380","DOI":"10.1002\/prot.23046","article-title":"Incorporation of evolutionary information into Rosetta comparative modeling","volume":"79","author":"J. Thompson","year":"2011","journal-title":"Proteins"},{"issue":"5742","key":"pone.0273322.ref061","doi-asserted-by":"crossref","first-page":"1868","DOI":"10.1126\/science.1113801","article-title":"Toward high-resolution de novo structure prediction for small proteins","volume":"309","author":"P. Bradley","year":"2005","journal-title":"Science"},{"key":"pone.0273322.ref062","unstructured":"Schrodinger, LLC. The PyMOL Molecular Graphics System, Version 1.8. 2015."},{"issue":"1","key":"pone.0273322.ref063","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1002\/pro.3943","article-title":"UCSF ChimeraX: Structure visualization for researchers, educators, and developers","volume":"30","author":"E.F. Pettersen","year":"2021","journal-title":"Protein science: a publication of the Protein Society"},{"key":"pone.0273322.ref064","unstructured":"Karlsson, R., et al. Analyzing a kinetic titration series using affinity biosensors. (0003\u20132697 (Print))."},{"issue":"5","key":"pone.0273322.ref065","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/S0969-2126(96)00060-3","article-title":"The crystal structure of bacteriophage Q\u03b2 at 3.5 \u00e5 resolution","volume":"4","author":"R. Golmohammadi","year":"1996","journal-title":"Structure"},{"issue":"6","key":"pone.0273322.ref066","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/S1097-2765(01)80009-5","article-title":"The Crystal Structure of the Human Hepatitis B Virus Capsid","volume":"3","author":"S.A. Wynne","year":"1999","journal-title":"Molecular Cell"},{"key":"pone.0273322.ref067","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/srep00005","article-title":"SplitCore: an exceptionally versatile viral nanoparticle for native whole protein display regardless of 3D structure","volume":"1","author":"A. 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Cid","year":"2021","journal-title":"Biomolecules"},{"key":"pone.0273322.ref074","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2018.02224","article-title":"Nanoparticle Vaccines Against Infectious Diseases","volume":"9","author":"R. Pati","year":"2018","journal-title":"Frontiers in Immunology"},{"issue":"1","key":"pone.0273322.ref075","doi-asserted-by":"crossref","first-page":"6","DOI":"10.2174\/2211738507666191024162042","article-title":"Nanoparticles and Vaccine Development","volume":"8","author":"M. Kheirollahpour","year":"2020","journal-title":"Pharm Nanotechnol"},{"issue":"5","key":"pone.0273322.ref076","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1080\/21645515.2018.1457595","article-title":"Four-year antibody persistence and response to a booster dose of a pentavalent MenABCWY vaccine administered to healthy adolescents and young adults","volume":"14","author":"X. S\u00e1ez-Llorens","year":"2018","journal-title":"Human vaccines & immunotherapeutics"},{"key":"pone.0273322.ref077","unstructured":"Caradonna, T.A.-O. and A.A.-O. Schmidt. Protein engineering strategies for rational immunogen design. (2059\u20130105 (Electronic))."},{"issue":"7","key":"pone.0273322.ref078","first-page":"2031","volume":"35","author":"P. Maurer","year":"2005","journal-title":"A therapeutic vaccine for nicotine dependence: preclinical efficacy, and Phase I safety and immunogenicity"},{"key":"pone.0273322.ref079","doi-asserted-by":"crossref","first-page":"103699","DOI":"10.1016\/j.ebiom.2021.103699","article-title":"Current and future nanoparticle vaccines for COVID-19","volume":"74","author":"M.N. 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(2076-393X (Print)).","DOI":"10.3390\/vaccines9040403"},{"issue":"1","key":"pone.0273322.ref082","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1038\/s41467-020-20654-7","article-title":"A COVID-19 vaccine candidate using SpyCatcher multimerization of the SARS-CoV-2 spike protein receptor-binding domain induces potent neutralising antibody responses","volume":"12","author":"T.K. Tan","year":"2021","journal-title":"Nature Communications"},{"key":"pone.0273322.ref083","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.smim.2017.08.014","article-title":"Major findings and recent advances in virus\u2013like particle (VLP)-based vaccines","volume":"34","author":"M.O. 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