{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T19:31:57Z","timestamp":1776799917458,"version":"3.51.2"},"reference-count":28,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2016,5,1]],"date-time":"2016-05-01T00:00:00Z","timestamp":1462060800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Food and Drug Administration Intramural Research Program"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Clin Vaccine Immunol"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>The spontaneous modification of proteins, such as deamidation of asparagine residues, can significantly affect the immunogenicity of protein-based vaccines. Using a \u201cgenetically deamidated\u201d form of recombinant protective antigen (rPA), we have previously shown that deamidation can decrease the immunogenicity of rPA, the primary component of new-generation anthrax vaccines. In this study, we investigated the biochemical and immunological mechanisms by which deamidation of rPA might decrease the immunogenicity of the protein. We found that loss of the immunogenicity of rPA vaccine was independent of the presence of adjuvant. We assessed the effect of deamidation on the immunodominant neutralizing B-cell epitopes of rPA and found that these epitopes were not significantly affected by deamidation. In order to assess the effect of deamidation on T-cell help for antibody production elicited by rPA vaccine, we examined the ability of the wild-type and genetically deamidated forms of rPA to serve as hapten carriers. We found that when wild-type and genetically deamidated rPA were modified to similar extents with 2,4-dinitrophenyl hapten (DNP) and then used to immunize mice, higher levels of anti-DNP antibodies were elicited by wild-type DNP-rPA than those elicited by the genetically deamidated DNP-rPA, indicating that wild-type rPA elicits more T-cell help than the genetically deamidated form of the protein. These results suggest that a decrease in the ability of deamidated rPA to elicit T-cell help for antibody production is a possible contributor to its lower immunogenicity.<\/jats:p>","DOI":"10.1128\/cvi.00701-15","type":"journal-article","created":{"date-parts":[[2016,2,25]],"date-time":"2016-02-25T04:13:58Z","timestamp":1456373638000},"page":"396-402","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":24,"title":["Mechanistic Analysis of the Effect of Deamidation on the Immunogenicity of Anthrax Protective Antigen"],"prefix":"10.1128","volume":"23","author":[{"given":"Anita","family":"Verma","sequence":"first","affiliation":[{"name":"Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miriam M.","family":"Ngundi","sequence":"additional","affiliation":[{"name":"Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Drusilla L.","family":"Burns","sequence":"additional","affiliation":[{"name":"Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2009.07.003"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.75.103004.142728"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.63.1.82-87.1995"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3004073"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(01)00234-1"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00469-14"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.4161\/hv.9777"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00863-12"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/jps.23422"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.98.3.944"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M500687200"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M501241200"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.193.11.1239"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-4347(98)00425-3"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2007.06.049"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.21432"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2006.02.013"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M008309200"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja8049063"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0161-5890(88)90109-5"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00003-08"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00174-12"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00513-09"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12356"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1334"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(01)00021-4"},{"key":"e_1_3_2_28_2","unstructured":"Food and Drug Administration. 2010. November 16 2010: Vaccines and related biological products advisory committee meeting transcript. http:\/\/www.fda.gov\/AdvisoryCommittees\/CommitteesMeetingMaterials\/BloodVaccinesandOtherBiologics\/VaccinesandRelatedBiologicalProductsAdvisoryCommittee\/ucm237045.htm."},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(03)00109-9"}],"container-title":["Clinical and Vaccine Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/CVI.00701-15","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/CVI.00701-15","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T20:42:43Z","timestamp":1627591363000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/CVI.00701-15"}},"subtitle":[],"editor":[{"given":"P. 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