{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T07:04:35Z","timestamp":1767855875593,"version":"3.49.0"},"reference-count":56,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T00:00:00Z","timestamp":1755648000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Allergy and Infectious Diseases","award":["AI106153"],"award-info":[{"award-number":["AI106153"]}]},{"name":"National Institute of Allergy and Infectious Diseases","award":["AI142939"],"award-info":[{"award-number":["AI142939"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Anthrax remains a serious bioterrorism threat for which new and thermostable vaccines are needed. We previously demonstrated that immunization of rabbits with multiple-antigenic-peptide (MAP) vaccines elicit antibody (Ab) against the loop-neutralizing-determinant (LND), a cryptic linear neutralizing epitope in the 2\u03b22-2\u03b23 loop of protective antigen (PA) from Bacillus anthracis (B. anthracis), which mediates the complete protection of rabbits from inhalation spore challenge with B. anthracis Ames strain. Importantly, LND-specific Ab is not significantly elicited with PA-based vaccines. In the current study, we sought to identify a second unique neutralizing epitope which would also not overlap with the neutralizing specificities elicited by PA-based vaccines, and which could be combined with an LND vaccine as a prototype bivalent vaccine for anthrax. We evaluated linear peptide sequences in the \u03b12-\u03b13 helices of domain 3 of lethal factor (LF) in the form of virus-like particle (VLP) vaccines. Immunogenicity studies confirmed the presence of a 20-mer peptide sequence that is capable of eliciting protective levels of neutralizing Ab following two immunizations of rabbits using human-use adjuvants, and lyophilization of the VLPs did not diminish their immunogenicity. To our knowledge, this is the first demonstration that immunization with linear peptide sequences from LF can elicit protective levels of neutralizing Ab in vivo.<\/jats:p>","DOI":"10.3390\/toxins17080422","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T07:50:46Z","timestamp":1755676246000},"page":"422","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Lyophilizable Nanoparticle Vaccine Specific for a Novel Linear Neutralizing Epitope in the \u03b12-\u03b13 Helices of Domain 3 of Lethal Factor from Bacillus anthracis"],"prefix":"10.3390","volume":"17","author":[{"given":"Jon","family":"Oscherwitz","sequence":"first","affiliation":[{"name":"Division of Hematology-Oncology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48105, USA"},{"name":"Veterans Administration Ann Arbor Healthcare System, 2215 Fuller Road, Ann Arbor, MI 48105, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kemp","family":"Cease","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48105, USA"},{"name":"Veterans Administration Ann Arbor Healthcare System, 2215 Fuller Road, Ann Arbor, MI 48105, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Milich","sequence":"additional","affiliation":[{"name":"VLP Biotech, Inc., 3030 Bunker Hill St., Ste 117D, San Diego, CA 92109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7113-6998","authenticated-orcid":false,"given":"Thomas","family":"Braun","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Michigan, Ann Arbor, MI 48105, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fen","family":"Yu","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48105, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3803-9157","authenticated-orcid":false,"given":"David","family":"Whitacre","sequence":"additional","affiliation":[{"name":"VLP Biotech, Inc., 3030 Bunker Hill St., Ste 117D, San Diego, CA 92109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Head, B.M., Rubinstein, E., and Meyers, A.F. 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