{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T18:10:46Z","timestamp":1781115046920,"version":"3.54.1"},"reference-count":52,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    MAPS technology represents an innovative approach for the development of polysaccharide-based vaccines, relying on the affinity interaction between biotin and rhizavidin (rhavi), with potential for enhanced coverage through the incorporation of pathogen-specific proteins. Due to its flexibility, this platform is particularly attractive for the development of multivalent vaccines, as it is required for\n                    <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                    , a multidrug-resistant bacterium highlighted as prevalent cause of neonatal sepsis in low- and middle-income countries, against which no vaccines are currently available. In this work MrkA, a potential protective pathogen-specific protein antigen, was combined in a MAPS complex with K2 as model for\n                    <jats:italic>Klebsiella<\/jats:italic>\n                    K-antigen. The impact of sugar chain length, protein to polysaccharide ratio, and MAPS complex size on the immune response elicited in animal models was evaluated. Results showed that longer polysaccharides and higher protein\/K-antigen ratios enhanced the immunogenicity in rabbits. Different proteins, i.e., rhavi alone and CP1-rhavi from\n                    <jats:italic>Streptococcus pneumoniae<\/jats:italic>\n                    , were also evaluated as carrier, showing that the protein antigen fused to rhavi can play a significant role on the resulting MAPS polysaccharide specific immunogenicity. Passive transfer of rabbit polyclonal sera from the most immunogenic MAPS complex was able to protect mice from challenge with a K2 clinical isolate. This work supports the rational design of a K-antigen MAPS-based vaccine against\n                    <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014289","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T17:45:14Z","timestamp":1781113514000},"page":"e1014289","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Understanding the impact of Klebsiella pneumoniae K-Antigen based MAPS vaccine design on the immune response in animal models"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1248-5389","authenticated-orcid":true,"given":"Elena","family":"Palmieri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianina Florentina","family":"Belciug","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Nonne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Massai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Valensin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"De Rosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Berlanda Scorza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Rondini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Carducci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Rossi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Micoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6112-6841","authenticated-orcid":true,"given":"Carlo","family":"Giannelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"issue":"4","key":"ppat.1014289.ref001","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1038\/s41564-021-00870-7","article-title":"Characterization of antimicrobial-resistant Gram-negative bacteria that cause neonatal sepsis in seven low- and middle-income countries","volume":"6","author":"K Sands","year":"2021","journal-title":"Nat Microbiol"},{"key":"ppat.1014289.ref002","doi-asserted-by":"crossref","DOI":"10.1016\/j.vaccine.2024.02.072","article-title":"Vaccine value profile for Klebsiella pneumoniae","volume":"42","author":"Z Dangor","year":"2024","journal-title":"Vaccine"},{"key":"ppat.1014289.ref003","doi-asserted-by":"crossref","DOI":"10.3389\/fmed.2021.634349","article-title":"Neonatal sepsis: the impact of carbapenem-resistant and hypervirulent Klebsiella pneumoniae","volume":"8","author":"S Mukherjee","year":"2021","journal-title":"Front Med"},{"key":"ppat.1014289.ref004","doi-asserted-by":"crossref","DOI":"10.1097\/INF.0b013e3181958755","article-title":"Burden of neonatal infections in developing countries: a review of evidence from community-based studies","volume":"28","author":"D Thaver","year":"2009","journal-title":"Pediatr Infect Dis J"},{"issue":"10369","key":"ppat.1014289.ref005","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.1016\/S0140-6736(22)02185-7","article-title":"Global mortality associated with 33 bacterial pathogens in 2019: a systematic analysis for the Global Burden of Disease Study 2019","volume":"400","author":"GBD 2019 Antimicrobial Resistance Collaborators","year":"2022","journal-title":"Lancet"},{"issue":"3","key":"ppat.1014289.ref006","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgph.0001612","article-title":"Causes of death identified in neonates enrolled through Child Health and Mortality Prevention Surveillance (CHAMPS), December 2016 - December 2021","volume":"3","author":"S Mahtab","year":"2023","journal-title":"PLOS Global Public Health"},{"issue":"5","key":"ppat.1014289.ref007","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1004239","article-title":"Global, regional, and national estimates of the impact of a maternal Klebsiella pneumoniae vaccine: A Bayesian modeling analysis","volume":"20","author":"CK Kumar","year":"2023","journal-title":"PLoS Med"},{"issue":"7","key":"ppat.1014289.ref008","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1080\/14760584.2019.1635460","article-title":"Progress towards the development of Klebsiella vaccines","volume":"18","author":"M Choi","year":"2019","journal-title":"Expert Rev Vaccines"},{"issue":"8","key":"ppat.1014289.ref009","doi-asserted-by":"crossref","first-page":"4042","DOI":"10.3390\/ijms22084042","article-title":"Prophylaxis and treatment against Klebsiella pneumoniae: current insights on this emerging anti-microbial resistant global threat","volume":"22","author":"V Arato","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"2","key":"ppat.1014289.ref010","doi-asserted-by":"crossref","DOI":"10.1093\/infdis\/jiaf600","article-title":"Safety and immunogenicity of a Klebsiella pneumoniae tetravalent bioconjugate vaccine (Kleb4V) administered to healthy adults: a first-in-human phase I\/II randomized and controlled study","volume":"233","author":"C Alaimo","year":"2026","journal-title":"J Infect Dis"},{"issue":"10","key":"ppat.1014289.ref011","doi-asserted-by":"crossref","first-page":"4495","DOI":"10.1128\/iai.62.10.4495-4499.1994","article-title":"Polysaccharide capsule-mediated resistance to opsonophagocytosis in Klebsiella pneumoniae","volume":"62","author":"P Domenico","year":"1994","journal-title":"Infect Immun"},{"issue":"5","key":"ppat.1014289.ref012","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.02516-21","article-title":"Capsule promotes intracellular survival and vascular endothelial cell translocation during invasive pneumococcal disease","volume":"12","author":"T Brissac","year":"2021","journal-title":"mBio"},{"key":"ppat.1014289.ref013","doi-asserted-by":"crossref","first-page":"15573","DOI":"10.1038\/srep15573","article-title":"Genetic analysis of capsular polysaccharide synthesis gene clusters in 79 capsular types of Klebsiella spp","volume":"5","author":"Y-J Pan","year":"2015","journal-title":"Sci Rep"},{"issue":"12","key":"ppat.1014289.ref014","article-title":"Identification of Klebsiella capsule synthesis loci from whole genome data","volume":"2","author":"KL Wyres","year":"2016","journal-title":"Microb Genom"},{"issue":"3","key":"ppat.1014289.ref015","first-page":"000800","article-title":"Kaptive 2.0: updated capsule and lipopolysaccharide locus typing for the Klebsiella pneumoniae species complex","volume":"8","author":"MMC Lam","year":"2022","journal-title":"Microb Genom"},{"issue":"6","key":"ppat.1014289.ref016","article-title":"Fast and accurate in silico antigen typing with Kaptive 3","volume":"11","author":"TD Stanton","year":"2025","journal-title":"Microb Genom"},{"issue":"1","key":"ppat.1014289.ref017","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1004879","article-title":"Distribution of capsule and O types in Klebsiella pneumoniae causing neonatal sepsis in Africa and South Asia: a meta-analysis of genome-predicted serotype prevalence to inform potential vaccine coverage","volume":"23","author":"TD Stanton","year":"2026","journal-title":"PLoS Med"},{"issue":"1","key":"ppat.1014289.ref018","doi-asserted-by":"crossref","first-page":"91","DOI":"10.3390\/vaccines11010091","article-title":"A Bivalent MAPS Vaccine Induces Protective Antibody Responses against Salmonella Typhi and Paratyphi A","volume":"11","author":"F Zhang","year":"2022","journal-title":"Vaccines (Basel)"},{"issue":"11","key":"ppat.1014289.ref019","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.3390\/vaccines11111671","article-title":"Induction of broad immunity against invasive salmonella disease by a quadrivalent combination Salmonella MAPS vaccine targeting Salmonella Enterica Serovars Typhimurium, Enteritidis, Typhi, and Paratyphi A","volume":"11","author":"EM Boerth","year":"2023","journal-title":"Vaccines (Basel)"},{"issue":"10","key":"ppat.1014289.ref020","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.3390\/vaccines12101091","article-title":"Evaluation of a quadrivalent Shigella flexneri serotype 2a, 3a, 6, and Shigella sonnei O-specific polysaccharide and IpaB MAPS Vaccine","volume":"12","author":"EM Boerth","year":"2024","journal-title":"Vaccines (Basel)"},{"key":"ppat.1014289.ref021","volume-title":"InventorA maps vaccine targeting group b streptococcus (gbs) WO2024081906A12023","author":"C Thompson"},{"issue":"10","key":"ppat.1014289.ref022","doi-asserted-by":"crossref","first-page":"2560","DOI":"10.1016\/j.vaccine.2024.02.001","article-title":"Safety, tolerability and immunogenicity of a novel 24-valent pneumococcal vaccine in toddlers: A phase 1 randomized controlled trial","volume":"42","author":"D Borys","year":"2024","journal-title":"Vaccine"},{"key":"ppat.1014289.ref023","doi-asserted-by":"crossref","first-page":"126545","DOI":"10.1016\/j.vaccine.2024.126545","article-title":"Safety, reactogenicity, and immunogenicity of a novel 24-valent pneumococcal vaccine candidate in healthy, pneumococcal vaccine-na\u00efve Japanese adults: A phase 1 randomized dose-escalation trial","volume":"44","author":"D Borys","year":"2025","journal-title":"Vaccine"},{"issue":"31","key":"ppat.1014289.ref024","doi-asserted-by":"crossref","first-page":"4190","DOI":"10.1016\/j.vaccine.2022.05.079","article-title":"Phase 1\/2 study of a novel 24-valent pneumococcal vaccine in healthy adults aged 18 to 64 years and in older adults aged 65 to 85 years","volume":"40","author":"GR Chichili","year":"2022","journal-title":"Vaccine"},{"issue":"33","key":"ppat.1014289.ref025","doi-asserted-by":"crossref","first-page":"13564","DOI":"10.1073\/pnas.1307228110","article-title":"Multiple antigen-presenting system (MAPS) to induce comprehensive B- and T-cell immunity","volume":"110","author":"F Zhang","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"ppat.1014289.ref026","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0170529","article-title":"Anti-MrkA monoclonal antibodies reveal distinct structural and antigenic features of MrkA","volume":"12","author":"Q Wang","year":"2017","journal-title":"PLoS One"},{"issue":"2","key":"ppat.1014289.ref027","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.bbrc.2014.01.008","article-title":"Crystal structure of FliC flagellin from Pseudomonas aeruginosa and its implication in TLR5 binding and formation of the flagellar filament","volume":"444","author":"WS Song","year":"2014","journal-title":"Biochem Biophys Res Commun"},{"issue":"8","key":"ppat.1014289.ref028","article-title":"Novel Klebsiella pneumoniae and Pseudomonas aeruginosa MAPS vaccine combining O polysaccharides and pathogen-specific proteins","volume":"16","author":"MN Amin","year":"2025","journal-title":"mBio"},{"issue":"3","key":"ppat.1014289.ref029","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1042\/BJ20070076","article-title":"Rhizavidin from Rhizobium etli: the first natural dimer in the avidin protein family","volume":"405","author":"SH Helppolainen","year":"2007","journal-title":"Biochem J"},{"issue":"2","key":"ppat.1014289.ref030","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1080\/14787210.2019.1555470","article-title":"Hypervirulent Klebsiella pneumoniae: a new public health threat","volume":"17","author":"CM Marr","year":"2019","journal-title":"Expert Rev Anti Infect Ther"},{"issue":"1","key":"ppat.1014289.ref031","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s13073-019-0706-y","article-title":"Genomic surveillance for hypervirulence and multi-drug resistance in invasive Klebsiella pneumoniae from South and Southeast Asia","volume":"12","author":"KL Wyres","year":"2020","journal-title":"Genome Med"},{"issue":"10","key":"ppat.1014289.ref032","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.3390\/vaccines9101114","article-title":"Use of stability modeling to support accelerated vaccine development and supply","volume":"9","author":"C Campa","year":"2021","journal-title":"Vaccines (Basel)"},{"issue":"7","key":"ppat.1014289.ref033","doi-asserted-by":"crossref","first-page":"707","DOI":"10.3390\/vaccines12070707","article-title":"Modeling 1-cyano-4-dimethylaminopyridine tetrafluoroborate (CDAP) chemistry to design glycoconjugate vaccines with desired structural and immunological characteristics","volume":"12","author":"R Nappini","year":"2024","journal-title":"Vaccines (Basel)"},{"issue":"4","key":"ppat.1014289.ref034","first-page":"256","article-title":"Development and application of a high-throughput method for the purification and analysis of surface carbohydrates from Klebsiella pneumoniae","volume":"13","author":"F Nonne","year":"2024","journal-title":"Biology (Basel)"},{"issue":"3","key":"ppat.1014289.ref035","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.vaccine.2021.12.007","article-title":"The half-life of maternal transplacental antibodies against diphtheria, tetanus, and pertussis in infants: an individual participant data meta-analysis","volume":"40","author":"B Oguti","year":"2022","journal-title":"Vaccine"},{"issue":"3","key":"ppat.1014289.ref036","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1056\/NEJMoa2116045","article-title":"Potential for maternally administered vaccine for infant group B Streptococcus","volume":"389","author":"SA Madhi","year":"2023","journal-title":"N Engl J Med"},{"issue":"1","key":"ppat.1014289.ref037","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1099\/00222615-20-1-113","article-title":"Antigenic relationships among type-3 fimbriae of Enterobacteriaceae revealed by immunoelectronmicroscopy","volume":"20","author":"DC Old","year":"1985","journal-title":"J Med Microbiol"},{"issue":"2","key":"ppat.1014289.ref038","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1099\/00222615-20-2-203","article-title":"A comparative study of the type-3 fimbriae of Klebsiella species","volume":"20","author":"DC Old","year":"1985","journal-title":"J Med Microbiol"},{"issue":"2","key":"ppat.1014289.ref039","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.vascn.2011.12.001","article-title":"Developmental and reproductive toxicity testing of vaccines","volume":"65","author":"P Barrow","year":"2012","journal-title":"J Pharmacol Toxicol Methods"},{"issue":"5","key":"ppat.1014289.ref040","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s12276-018-0094-1","article-title":"The wide utility of rabbits as models of human diseases","volume":"50","author":"PJ Esteves","year":"2018","journal-title":"Exp Mol Med"},{"issue":"35","key":"ppat.1014289.ref041","doi-asserted-by":"crossref","first-page":"4235","DOI":"10.1016\/j.vaccine.2016.06.039","article-title":"Preclinical studies on new proteins as carrier for glycoconjugate vaccines","volume":"34","author":"M Tontini","year":"2016","journal-title":"Vaccine"},{"issue":"11","key":"ppat.1014289.ref042","doi-asserted-by":"crossref","first-page":"1800","DOI":"10.1093\/infdis\/jiw021","article-title":"Target-agnostic identification of functional monoclonal antibodies against Klebsiella pneumoniae multimeric MrkA fimbrial subunit","volume":"213","author":"Q Wang","year":"2016","journal-title":"J Infect Dis"},{"issue":"3","key":"ppat.1014289.ref043","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.ijmm.2005.04.001","article-title":"Klebsiella pneumoniae type 3 fimbria-mediated immunity to infection in the murine model of respiratory disease","volume":"295","author":"H Lavender","year":"2005","journal-title":"Int J Med Microbiol"},{"key":"ppat.1014289.ref044","doi-asserted-by":"crossref","first-page":"127075","DOI":"10.1016\/j.vaccine.2025.127075","article-title":"In-silico and experimental analysis of Klebsiella pneumoniae fimbriae subunits for vaccine development","volume":"53","author":"L Assoni","year":"2025","journal-title":"Vaccine"},{"key":"ppat.1014289.ref045","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.ijbiomac.2020.03.196","article-title":"Determination of the capsular polysaccharide structure of the Klebsiella pneumoniae ST512 representative strain KPB-1 and assignments of the glycosyltransferases functions","volume":"155","author":"B Bellich","year":"2020","journal-title":"Int J Biol Macromol"},{"issue":"1","key":"ppat.1014289.ref046","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.ab.2012.10.038","article-title":"A scalable method for O-antigen purification applied to various Salmonella serovars","volume":"434","author":"F Micoli","year":"2013","journal-title":"Anal Biochem"},{"issue":"3","key":"ppat.1014289.ref047","doi-asserted-by":"crossref","DOI":"10.1128\/mbio.03790-21","article-title":"Carrier proteins facilitate the generation of antipolysaccharide immunity via multiple mechanisms","volume":"13","author":"F Zhang","year":"2022","journal-title":"mBio"},{"issue":"3","key":"ppat.1014289.ref048","doi-asserted-by":"crossref","first-page":"52","DOI":"10.3390\/mps8030052","article-title":"Development and characterization of a ten-plex assay to measure Klebsiella pneumoniae antigen-specific IgG in human sera","volume":"8","author":"L Rovetini","year":"2025","journal-title":"Methods Protoc"},{"issue":"2","key":"ppat.1014289.ref049","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0172163","article-title":"Development of a high-throughput method to evaluate serum bactericidal activity using bacterial ATP measurement as survival readout","volume":"12","author":"F Necchi","year":"2017","journal-title":"PLoS One"},{"issue":"2","key":"ppat.1014289.ref050","doi-asserted-by":"crossref","first-page":"14","DOI":"10.3390\/ht9020014","article-title":"Intra-Laboratory evaluation of luminescence based high-throughput serum bactericidal assay (L-SBA) to determine bactericidal activity of human sera against Shigella","volume":"9","author":"O Rossi","year":"2020","journal-title":"High Throughput"},{"issue":"5","key":"ppat.1014289.ref051","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1641\/0006-3568(2001)051[0341:LNDATS]2.0.CO;2","article-title":"Log-normal distributions across the sciences: keys and clues: on the charms of statistics, and how mechanical models resembling gambling machines offer a link to a handy way to characterize log-normal distributions, which can provide deeper insight into variability and probability\u2014normal or log-normal: that is the question","volume":"51","author":"E Limpert","year":"2001","journal-title":"BioScience"},{"issue":"3","key":"ppat.1014289.ref052","doi-asserted-by":"crossref","first-page":"100049","DOI":"10.1016\/j.pharmr.2025.100049","article-title":"Analyzing lognormal data: a nonmathematical practical guide","volume":"77","author":"HJ Motulsky","year":"2025","journal-title":"Pharmacol Rev"}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1014289","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T17:45:22Z","timestamp":1781113522000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1014289"}},"subtitle":[],"editor":[{"given":"Gerald B","family":"Pier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,6,10]]},"references-count":52,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6,10]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1014289","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,10]]}}}