{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T18:37:29Z","timestamp":1792521449995,"version":"4.5.0"},"reference-count":116,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Because hepatitis B virus (HBV) remains a major global health burden, innovative strategies are essential to achieve the World Health Organization\u2019s goal of eliminating viral hepatitis and closing persistent coverage gaps for injectable vaccines. While parenteral administration remains the gold standard for immunization, constraints such as cold-chain dependence and needle-associated barriers limit its reach, particularly in resource-constrained environments. This review summarizes work aimed at a plant-produced orally delivered vaccine as a transformative, scalable step towards global hepatitis B elimination. Early studies demonstrated proof of concept for the oral delivery of plant-produced hepatitis B vaccine candidates, including human trials using lettuce and potato as the host, but they were limited by low antigen yields and instability. In contrast, maize-produced antigens represent a significant advancement, achieving high levels of accumulation and utilizing the seed\u2019s natural desiccation physiology for bioencapsulation to protect the antigen from digestion in the gastrointestinal tract. Mechanistically, this platform enables timed antigen release in the duodenum, promoting M-cell uptake and CD103+ (cells expressing CD103 known as integrin alpha E) dendritic cell (DC) presentation, thus encouraging immunogenic programming over oral tolerance. In addition, defatting the grain by supercritical fluid extraction further improves antigen thermostability up to 45 \u00b0C for one month and ambient temperatures for one year, maintaining structural integrity under extreme conditions in accordance with the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) stability guidelines. Current recommendations for immunization are for three parenteral administrations using the hepatitis B surface antigen (HBsAg). The primary dose is usually given shortly after birth as a part of a multivalent vaccine. Therefore, initial studies for the oral plant-based vaccine have focused on using an oral boost after the parenteral prime. Data to support this premise are summarized along with co-administration of an oral and parental administration to elicit a stronger immune response. By overcoming past issues related to dose density and stability, this scalable, needle-free platform offers a practical way to eliminate global hepatitis B virus (HBV) transmission, especially in resource-constrained environments.<\/jats:p>","DOI":"10.3390\/vaccines14070578","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T08:26:15Z","timestamp":1782807975000},"page":"578","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Advancing Global Hepatitis B Elimination: The Case for Using Maize as a Low-Cost, Heat-Stable, and Scalable Oral Vaccine"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-1963-7671","authenticated-orcid":false,"given":"Muneaki","family":"Watanabe","sequence":"first","affiliation":[{"name":"Applied Biotechnology Institute Inc., San Luis Obispo, CA 93407, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Howard","sequence":"additional","affiliation":[{"name":"Applied Biotechnology Institute Inc., San Luis Obispo, CA 93407, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.amepre.2009.01.037","article-title":"Physician practices regarding adult hepatitis B vaccination: A national survey","volume":"36","author":"Daley","year":"2009","journal-title":"Am. 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