{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T06:35:12Z","timestamp":1776926112332,"version":"3.51.2"},"reference-count":265,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Virus-like particles (VLPs) have emerged as a versatile and clinically validated platform for developing safe, effective vaccines against infectious diseases. However, the expanding toolkit of VLP engineering strategies\u2013spanning genetic fusion, modular conjugation, and nucleic acid encapsulation\u2013creates a critical need for a rational selection framework to match technological strengths with specific vaccine objectives. This review addresses this gap by constructing a comparative decision-making framework centered on four core engineering dimensions: cargo flexibility, loading specificity, functional efficiency, and manufacturability. We systematically juxtapose two principal technology streams: (1) the display of protein antigens (through genetic, chemical, and bio-conjugation) and (2) the encapsulation of nucleic acid cargo (via physical, electrostatic, and programmable packaging mechanisms), evaluating each within this unified framework. This technological dissection is directly linked to the development landscape of VLP-based vaccines against major pathogens\u2013including HBV, HPV, malaria, influenza, and SARS-CoV-2\u2013illustrating how strategic choices at the engineering level fundamentally underpin immunogenic potency and translational success. By sequentially considering immunological objectives, antigen compatibility, surface display modality, interior cargo integration, and manufacturing constraints, this framework facilitates rational, stepwise VLP vaccine design. Looking forward, we discuss emerging trends toward modular and computationally guided platforms for antigen placement and scaffold design. By integrating a structured technology assessment with translational insights, this review aims to provide a practical roadmap for the rational design and accelerated development of next-generation, broadly protective VLP-based vaccines.<\/jats:p>","DOI":"10.3389\/fmicb.2026.1795711","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T05:35:56Z","timestamp":1776922556000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Engineering strategies and decision frameworks for virus-like particle-based vaccines against infectious diseases"],"prefix":"10.3389","volume":"17","author":[{"given":"YiYan","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pathophysiology, School of Basic Medical Sciences, Lanzhou University","place":["Lanzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanan","family":"Zhang","sequence":"additional","affiliation":[{"name":"The First Hospital of Lanzhou University","place":["Lanzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lijuan","family":"Liang","sequence":"additional","affiliation":[{"name":"The First Clinical Medical School of Gansu University of Chinese Medicine","place":["Lanzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han","family":"Zhang","sequence":"additional","affiliation":[{"name":"Cuiying Honors College of Lanzhou University","place":["Lanzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianjiao","family":"Zhang","sequence":"additional","affiliation":[{"name":"The First Hospital of Lanzhou University","place":["Lanzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xifeng","family":"Rong","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Basic Medicine Sciences, Lanzhou University","place":["Lanzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JiYing","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Basic Medicine Sciences, Lanzhou University","place":["Lanzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youjun","family":"Mi","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, School of Basic Medical Sciences, Lanzhou University","place":["Lanzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s12936-024-04846-w","article-title":"perspective on Oxford\u2019s R21\/Matrix-M\u2122 malaria vaccine and the future of global eradication efforts.","volume":"23","author":"Aderinto","year":"2024","journal-title":"Malar J."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2284","DOI":"10.1056\/NEJMoa1208394","article-title":"A phase 3 trial of RTS,S\/AS01 malaria vaccine in African infants.","volume":"367","author":"Agnandji","year":"2012","journal-title":"N. 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