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Traditional adjuvants enhance vaccine efficacy but may have limitations related to safety, tolerability, or restricted immune activation. Natural extracts derived from plants, marine organisms, fungi, and algae are gaining attention as novel adjuvants due to their ability to modulate both innate and adaptive immunity with low toxicity. This review highlights key natural compounds such as polysaccharides (fucoidan, chitosan, Advax), saponins (QS\u201021, Matrix\u2010M), and flavonoids (naringenin) and their mechanisms of action, including activation of dendritic cells, cytokine induction, and enhancement of T and B cell responses. These extracts promote balanced Th1\/Th2 polarization, memory cell formation, and improved mucosal and systemic immunity. We also summarize in\u00a0vitro and in\u00a0vivo methods used for adjuvant screening, including immune cell activation assays, T\/B cell co\u2010culture systems, and murine vaccination models. Natural extract\u2010based adjuvants offer formulation flexibility for various vaccine platforms and delivery routes, including intranasal and intramuscular administration. Their favorable safety profiles, immunostimulatory potency, and capacity to enhance cross\u2010protective immunity position them as strong candidates for next\u2010generation adjuvants for influenza vaccines. Ongoing research may enable their broader application in improving vaccine performance across diverse populations.<\/jats:p>","DOI":"10.1002\/fsn3.71840","type":"journal-article","created":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T09:16:07Z","timestamp":1779527767000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immunopotentiation by Natural Extracts: Mechanisms and Applications in Influenza Vaccine Adjuvant Development"],"prefix":"10.1002","volume":"14","author":[{"given":"Thi Len","family":"Ho","sequence":"first","affiliation":[{"name":"Interdisciplinary Graduate Program in Advanced Convergence Technology &amp; Science Jeju National University  Jeju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1081-904X","authenticated-orcid":false,"given":"Eun\u2010Ju","family":"Ko","sequence":"additional","affiliation":[{"name":"Interdisciplinary 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