{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T15:00:56Z","timestamp":1777561256313,"version":"3.51.4"},"reference-count":67,"publisher":"Frontiers Media SA","content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"DOI":"10.3389\/fimmu.2018.00562","type":"journal-article","created":{"date-parts":[[2018,3,20]],"date-time":"2018-03-20T14:07:43Z","timestamp":1521554863000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":60,"title":["Trimethyl Chitosan Nanoparticles Encapsulated Protective Antigen Protects the Mice Against Anthrax"],"prefix":"10.3389","volume":"9","author":[{"given":"Anshu","family":"Malik","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manish","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajesh","family":"Mani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Himanshu","family":"Gogoi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rakesh","family":"Bhatnagar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2018,3,20]]},"reference":[{"key":"B1","volume-title":"Guidelines for the Surveillance and Control of Anthrax in Humans and Animals","author":"Turnbull","year":"1998"},{"key":"B2","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1016\/S2221-1691(11)60109-3","article-title":"Anthrax: an update","volume":"1","author":"Kamal","year":"2011","journal-title":"Asian Pac J Trop Biomed"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.3201\/eid0810.020353","article-title":"Investigation of bioterrorism-related anthrax, United States, 2001: epidemiologic findings","volume":"8","author":"Jernigan","year":"2002","journal-title":"Emerg Infect Dis"},{"key":"B4","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1086\/523578","article-title":"Countering anthrax: vaccines and immunoglobulins","volume":"46","author":"Plotkin","year":"2008","journal-title":"Clin Infect Dis"},{"key":"B5","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1128\/CVI.00321-07","article-title":"Neutralizing activity of vaccine-induced antibodies to two Bacillus anthracis toxin components, lethal factor and edema factor","volume":"15","author":"Taft","year":"2008","journal-title":"Clin Vaccine Immunol"},{"key":"B6","volume-title":"The Anthrax Vaccine: Is It Safe? Does It Work?","author":"Strom","year":"2002"},{"key":"B7","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/978-3-662-05767-4_3","article-title":"Anthrax vaccines","volume-title":"Anthrax","author":"Friedlander","year":"2002"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1747","DOI":"10.1016\/S0041-0101(01)00161-1","article-title":"Toxins of Bacillus anthracis","volume":"39","author":"Brossier","year":"2001","journal-title":"Toxicon"},{"key":"B9","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/j.tim.2014.02.012","article-title":"Anthrax lethal and edema toxins in anthrax pathogenesis","volume":"22","author":"Liu","year":"2014","journal-title":"Trends Microbiol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1086\/426865","article-title":"Protective immunization against inhalational anthrax: a comparison of minimally invasive delivery platforms","volume":"191","author":"Mikszta","year":"2005","journal-title":"J Infect Dis"},{"key":"B11","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1038\/nmat3775","article-title":"Engineering synthetic vaccines using cues from natural immunity","volume":"12","author":"Irvine","year":"2013","journal-title":"Nat Mater"},{"key":"B12","doi-asserted-by":"publisher","first-page":"13","DOI":"10.3389\/fcimb.2013.00013","article-title":"Vaccine delivery using nanoparticles","volume":"3","author":"Gregory","year":"2013","journal-title":"Front Cell Infect Microbiol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1016\/j.addr.2007.05.017","article-title":"Nanotechnology in vaccine delivery","volume":"60","author":"Peek","year":"2008","journal-title":"Adv Drug Deliv Rev"},{"key":"B14","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.addr.2009.11.009","article-title":"Chitosan-based delivery systems for protein therapeutics and antigens","volume":"62","author":"Amidi","year":"2010","journal-title":"Adv Drug Deliv Rev"},{"key":"B15","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/j.jconrel.2012.01.043","article-title":"PLGA-based nanoparticles: an overview of biomedical applications","volume":"161","author":"Danhier","year":"2012","journal-title":"J Control Release"},{"key":"B16","doi-asserted-by":"publisher","first-page":"3129","DOI":"10.1016\/j.biomaterials.2009.03.013","article-title":"Influence of the degree of acetylation on the enzymatic degradation and in vitro biological properties of trimethylated chitosans","volume":"30","author":"Verheul","year":"2009","journal-title":"Biomaterials"},{"key":"B17","doi-asserted-by":"publisher","first-page":"3642","DOI":"10.1016\/j.biomaterials.2008.05.026","article-title":"Synthesis, characterization and in vitro biological properties of O-methyl free N, N, N-trimethylated chitosan","volume":"29","author":"Verheul","year":"2008","journal-title":"Biomaterials"},{"key":"B18","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.jconrel.2010.01.027","article-title":"Role of trimethylated chitosan (TMC) in nasal residence time, local distribution and toxicity of an intranasal influenza vaccine","volume":"144","author":"Hagenaars","year":"2010","journal-title":"J Control Release"},{"key":"B19","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.vaccine.2006.06.086","article-title":"N-trimethyl chitosan (TMC) nanoparticles loaded with influenza subunit antigen for intranasal vaccination: biological properties and immunogenicity in a mouse model","volume":"25","author":"Amidi","year":"2007","journal-title":"Vaccine"},{"key":"B20","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1016\/j.ejps.2011.10.001","article-title":"A step-by-step approach to study the influence of N-acetylation on the adjuvanticity of N, N, N-trimethyl chitosan (TMC) in an intranasal nanoparticulate influenza virus vaccine","volume":"45","author":"Verheul","year":"2012","journal-title":"Eur J Pharm Sci"},{"key":"B21","doi-asserted-by":"publisher","first-page":"5341","DOI":"10.1016\/j.vaccine.2012.06.035","article-title":"Hepatitis B surface antigen nanoparticles coated with chitosan and trimethyl chitosan: impact of formulation on physicochemical and immunological characteristics","volume":"30","author":"Tafaghodi","year":"2012","journal-title":"Vaccine"},{"key":"B22","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.jconrel.2009.05.011","article-title":"Mechanistic study of the adjuvant effect of biodegradable nanoparticles in mucosal vaccination","volume":"138","author":"Sl\u00fctter","year":"2009","journal-title":"J Control Release"},{"key":"B23","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1016\/j.ejps.2011.10.003","article-title":"Adjuvanted, antigen loaded N-trimethyl chitosan nanoparticles for nasal and intradermal vaccination: adjuvant-and site-dependent immunogenicity in mice","volume":"45","author":"Bal","year":"2012","journal-title":"Eur J Pharm Sci"},{"key":"B24","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/j.jconrel.2009.08.018","article-title":"Relationship between structure and adjuvanticity of N, N, N-trimethyl chitosan (TMC) structural variants in a nasal influenza vaccine","volume":"140","author":"Hagenaars","year":"2009","journal-title":"J Control Release"},{"key":"B25","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1016\/j.jconrel.2009.11.018","article-title":"Efficient induction of immune responses through intradermal vaccination with N-trimethyl chitosan containing antigen formulations","volume":"142","author":"Bal","year":"2010","journal-title":"J Control Release"},{"key":"B26","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.jconrel.2010.01.007","article-title":"Conjugation of ovalbumin to trimethyl chitosan improves immunogenicity of the antigen","volume":"143","author":"Sl\u00fctter","year":"2010","journal-title":"J Control Release"},{"key":"B27","doi-asserted-by":"publisher","first-page":"3573","DOI":"10.4049\/jimmunol.0802113","article-title":"Chitin is a size-dependent regulator of macrophage TNF and IL-10 production","volume":"182","author":"Da Silva","year":"2009","journal-title":"The J Immunol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"4279","DOI":"10.4049\/jimmunol.181.6.4279","article-title":"TLR-2 and IL-17A in chitin-induced macrophage activation and acute inflammation","volume":"181","author":"Da Silva","year":"2008","journal-title":"J Immunol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"2630","DOI":"10.2174\/092986711795933740","article-title":"Aluminum vaccine adjuvants: are they safe?","volume":"18","author":"Tomljenovic","year":"2011","journal-title":"Curr Med Chem"},{"key":"B30","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1111\/j.0818-9641.2004.01272.x","article-title":"Vaccine adjuvants: current state and future trends","volume":"82","author":"Petrovsky","year":"2004","journal-title":"Immunol Cell Biol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1111\/j.0818-9641.2004.01286.x","article-title":"Aluminium compounds for use in vaccines","volume":"82","author":"Lindblad","year":"2004","journal-title":"Immunol Cell Biol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"284","DOI":"10.4049\/jimmunol.1501903","article-title":"A CpG-Ficoll nanoparticle adjuvant for anthrax protective antigen enhances immunogenicity and provides single-immunization protection against inhaled anthrax in monkeys","volume":"196","author":"Kachura","year":"2016","journal-title":"J Immunol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1217","DOI":"10.1007\/s11095-005-9078-7","article-title":"Nasal immunization with anthrax protective antigen protein adjuvanted with polyriboinosinic\u2013polyribocytidylic acid induced strong mucosal and systemic immunities","volume":"23","author":"Sloat","year":"2006","journal-title":"Pharm Res"},{"key":"B34","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/j.jconrel.2010.06.009","article-title":"Dual role of CpG as immune modulator and physical crosslinker in ovalbumin loaded N-trimethyl chitosan (TMC) nanoparticles for nasal vaccination","volume":"148","author":"Sl\u00fctter","year":"2010","journal-title":"J Control Release"},{"key":"B35","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/j.addr.2004.10.001","article-title":"Need for new vaccine formulations and potential of particulate antigen and DNA delivery systems","volume":"57","author":"Friede","year":"2005","journal-title":"Adv Drug Deliv Rev"},{"key":"B36","doi-asserted-by":"crossref","first-page":"16010","DOI":"10.1038\/npjvaccines.2016.10","article-title":"Intradermal immunisation using the TLR3-ligand poly (I: C) as adjuvant induces mucosal antibody responses and protects against genital HSV-2 infection","volume":"1","author":"Bardel","year":"2016","journal-title":"npj Vaccines"},{"key":"B37","doi-asserted-by":"publisher","first-page":"732","DOI":"10.1038\/35099560","article-title":"Recognition of double-stranded RNA and activation of NF-\u03baB by Toll-like receptor 3","volume":"413","author":"Alexopoulou","year":"2001","journal-title":"Nature"},{"key":"B38","doi-asserted-by":"publisher","first-page":"6065","DOI":"10.4049\/jimmunol.172.10.6065","article-title":"Toll-like receptor ligands directly promote activated CD4+ T cell survival","volume":"172","author":"Gelman","year":"2004","journal-title":"J Immunol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1097\/01.cji.0000156828.75196.0d","article-title":"Defining the antigen-specific T-cell response to vaccination and poly (I: C)\/TLR3 signaling: evidence of enhanced primary and memory CD8 T-cell responses and antitumor immunity","volume":"28","author":"Salem","year":"2005","journal-title":"J Immunother"},{"key":"B40","doi-asserted-by":"publisher","first-page":"10036","DOI":"10.3390\/ijerph111010036","article-title":"Aberrant production of Th1\/Th2\/Th17-related cytokines in serum of C57BL\/6 mice after short-term formaldehyde exposure","volume":"11","author":"Wei","year":"2014","journal-title":"Int J Environ Res Public Health"},{"key":"B41","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1111\/j.1600-065X.2008.00697.x","article-title":"Interleukin-2 in the development and control of inflammatory disease","volume":"226","author":"Hoyer","year":"2008","journal-title":"Immunol Rev"},{"key":"B42","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1097\/00130832-200212000-00004","article-title":"Cytokines and their role in lymphoid development, differentiation and homeostasis","volume":"2","author":"Hofmann","year":"2002","journal-title":"Curr Opin Allergy Clin Immunol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"3463","DOI":"10.4049\/jimmunol.175.6.3463","article-title":"Directing transition from innate to acquired immunity: defining a role for IL-6","volume":"175","author":"Jones","year":"2005","journal-title":"J Immunol"},{"key":"B44","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/0144-8617(85)90037-2","article-title":"The N-permethylation of chitosan and the preparation of N-trimethyl chitosan iodide","volume":"5","author":"Muzzarelli","year":"1985","journal-title":"Carbohydr Polym"},{"key":"B45","doi-asserted-by":"publisher","first-page":"6282","DOI":"10.1016\/j.vaccine.2010.06.121","article-title":"Nasal vaccination with N-trimethyl chitosan and PLGA based nanoparticles: nanoparticle characteristics determine quality and strength of the antibody response in mice against the encapsulated antigen","volume":"28","author":"Sl\u00fctter","year":"2010","journal-title":"Vaccine"},{"key":"B46","doi-asserted-by":"publisher","first-page":"e61885","DOI":"10.1371\/journal.pone.0061885","article-title":"A single-dose PLGA encapsulated protective antigen domain 4 nanoformulation protects mice against Bacillus anthracis spore challenge","volume":"8","author":"Manish","year":"2013","journal-title":"PLoS One"},{"key":"B47","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.jconrel.2005.11.014","article-title":"Preparation and characterization of protein-loaded N-trimethyl chitosan nanoparticles as nasal delivery system","volume":"111","author":"Amidi","year":"2006","journal-title":"J Control Release"},{"key":"B48","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.ejpb.2003.09.006","article-title":"Low molecular weight chitosan nanoparticles as new carriers for nasal vaccine delivery in mice","volume":"57","author":"Vila","year":"2004","journal-title":"Eur J Pharm Biopharm"},{"key":"B49","doi-asserted-by":"publisher","first-page":"5015","DOI":"10.1016\/S0142-9612(03)00408-3","article-title":"Preparation and modification of N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride nanoparticle as a protein carrier","volume":"24","author":"Xu","year":"2003","journal-title":"Biomaterials"},{"key":"B50","doi-asserted-by":"publisher","first-page":"1431","DOI":"10.1023\/A:1012128907225","article-title":"Chitosan and chitosan\/ethylene oxide-propylene oxide block copolymer nanoparticles as novel carriers for proteins and vaccines","volume":"14","author":"Calvo","year":"1997","journal-title":"Pharm Res"},{"key":"B51","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1002\/jps.20520","article-title":"Self-assembled polyelectrolyte nanocomplexes between chitosan derivatives and insulin","volume":"95","author":"Mao","year":"2006","journal-title":"J Pharm Sci"},{"key":"B52","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1016\/j.jconrel.2007.05.025","article-title":"Chitosan and trimethyl chitosan chloride (TMC) as adjuvants for inducing immune responses to ovalbumin in mice following nasal administration","volume":"121","author":"Boonyo","year":"2007","journal-title":"J Control Release"},{"key":"B53","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/j.nano.2015.10.009","article-title":"Immunostimulatory effect of tetanus toxoid loaded chitosan nanoparticles following microneedles assisted immunization","volume":"12","author":"Siddhapura","year":"2016","journal-title":"Nanomedicine"},{"key":"B54","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.1016\/j.progpolymsci.2012.04.004","article-title":"Strategies for effective oral insulin delivery with modified chitosan nanoparticles: a review","volume":"37","author":"Mukhopadhyay","year":"2012","journal-title":"Prog Polym Sci"},{"key":"B55","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.1007\/s11095-009-9845-y","article-title":"Physicochemical and immunological characterization of N, N, N-trimethyl chitosan-coated whole inactivated influenza virus vaccine for intranasal administration","volume":"26","author":"Hagenaars","year":"2009","journal-title":"Pharm Res"},{"key":"B56","doi-asserted-by":"publisher","first-page":"221","DOI":"10.2471\/BLT.10.079426","article-title":"Intradermal delivery of vaccines: potential benefits and current challenges","volume":"89","author":"Hickling","year":"2011","journal-title":"Bull World Health Organ"},{"key":"B57","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1111\/j.1365-2567.2007.02607.x","article-title":"Induction of potent cellular immune response in mice by hepatitis C virus NS3 protein with double-stranded RNA","volume":"122","author":"Jin","year":"2007","journal-title":"Immunology"},{"key":"B58","doi-asserted-by":"publisher","first-page":"1841","DOI":"10.1016\/j.vaccine.2009.01.044","article-title":"Toll-like receptor 3 is necessary for dsRNA adjuvant effects","volume":"27","author":"Salaun","year":"2009","journal-title":"Vaccine"},{"key":"B59","doi-asserted-by":"publisher","first-page":"2574","DOI":"10.1073\/pnas.0711976105","article-title":"The microbial mimic poly IC induces durable and protective CD4+ T cell immunity together with a dendritic cell targeted vaccine","volume":"105","author":"Trumpfheller","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B60","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.vaccine.2008.10.024","article-title":"A clinical grade poly I: C-analogue (Ampligen\u00ae) promotes optimal DC maturation and Th1-type T cell responses of healthy donors and cancer patients in vitro","volume":"27","author":"Navabi","year":"2009","journal-title":"Vaccine"},{"key":"B61","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1111\/j.1574-695X.2001.tb00535.x","article-title":"CpG ODN can re-direct the Th bias of established Th2 immune responses in adult and young mice","volume":"32","author":"Weeratna","year":"2001","journal-title":"FEMS Immunol Med Microbiol"},{"key":"B62","doi-asserted-by":"publisher","first-page":"15553","DOI":"10.1073\/pnas.95.26.15553","article-title":"CpG DNA can induce strong Th1 humoral and cell-mediated immune responses against hepatitis B surface antigen in young mice","volume":"95","author":"Millan","year":"1998","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B63","doi-asserted-by":"publisher","first-page":"1623","DOI":"10.1084\/jem.186.10.1623","article-title":"CpG oligodeoxynucleotides act as adjuvants that switch on T helper 1 (Th1) immunity","volume":"186","author":"Chu","year":"1997","journal-title":"J Exp Med"},{"key":"B64","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s11671-016-1554-y","article-title":"Construction and immunological evaluation of CpG-Au@ HBc virus-like nanoparticles as a potential vaccine","volume":"11","author":"Wang","year":"2016","journal-title":"Nanoscale Res Lett"},{"key":"B65","doi-asserted-by":"publisher","first-page":"4422","DOI":"10.4049\/jimmunol.0804318","article-title":"TLR3 ligand polyinosinic: polycytidylic acid induces IL-17A and IL-21 synthesis in human Th cells","volume":"183","author":"Holm","year":"2009","journal-title":"J Immunol"},{"key":"B66","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1111\/j.1398-9995.2012.02876.x","article-title":"Poly (I: C) promotes the production of IL-17A by murine CD1d-driven invariant NKT cells in airway inflammation","volume":"67","author":"Vultaggio","year":"2012","journal-title":"Allergy"},{"key":"B67","doi-asserted-by":"publisher","first-page":"1482","DOI":"10.1164\/rccm.200912-1877OC","article-title":"Chitin particles are multifaceted immune adjuvants","volume":"182","author":"Da Silva","year":"2010","journal-title":"Am J Respir Crit Care Med"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"http:\/\/journal.frontiersin.org\/article\/10.3389\/fimmu.2018.00562\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,3,20]],"date-time":"2018-03-20T14:07:46Z","timestamp":1521554866000},"score":1,"resource":{"primary":{"URL":"http:\/\/journal.frontiersin.org\/article\/10.3389\/fimmu.2018.00562\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,20]]},"references-count":67,"alternative-id":["10.3389\/fimmu.2018.00562"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2018.00562","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,20]]},"article-number":"562"}}