{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T18:52:19Z","timestamp":1784141539896,"version":"3.55.0"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T00:00:00Z","timestamp":1721088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds Zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Drug Deliv."],"abstract":"<jats:p>Due to the inherent risk of a further pandemic influenza outbreak, there is a need and growing interest in investigating combinations of prophylactic vaccines and novel adjuvants, particularly to achieve antigen dose sparing and improved immunogenicity. Influenza is a highly variable virus, where the specific vaccine target is constantly changing, representing a major challenge to influenza vaccine development. Currently, commercial inactivated influenza vaccines have a poor CD8<jats:sup>+<\/jats:sup> T response, which impacts cross-reactivity and the duration of response. Adjuvanted influenza vaccines can increase immune responses, thereby achieving better protection and cross-reactivity to help contain the spread of the disease. An early exploration of a hybrid cholesterol-PLGA nanoparticle delivery system containing the saponin tomatine and a NOD2 (nucleotide-binding oligomerization domain 2) agonist called SG101 was conducted. This combination was preliminarily evaluated for its ability to induce cellular immunity when combined with whole inactivated virus (WIV) influenza vaccine. After the adjuvants were manufactured using a single emulsion process, two formulations with different drug loadings were selected and physico-chemically characterized, showing sizes between 224 \u00b1 32 and 309 \u00b1 45\u00a0nm and different morphologies. After ensuring the lack of <jats:italic>in vitro<\/jats:italic> toxicity and hemolytic activity, a pilot <jats:italic>in vivo<\/jats:italic> assay evaluated the hybrid nanoparticle formulation for its ability to induce humoral and cellular immunity when combined with whole inactivated virus (WIV) H5N1 influenza vaccine by intramuscular administration in mice. Hemagglutinin inhibition (HAI) titers for adjuvanted groups showed no significant difference compared to the group vaccinated with the antigen alone. It was similar for CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T cell responses, although the high drug loading formulation induced higher titers of IFN\u03b3-positive CD8<jats:sup>+<\/jats:sup> T cells. These proof-of-concept results encourage further investigations to develop the hybrid formulation with increased or different loading ratios, to investigate manufacturing optimization, and to evaluate the role of the individual immunostimulatory compounds in immune responses.<\/jats:p>","DOI":"10.3389\/fddev.2024.1382266","type":"journal-article","created":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T04:50:51Z","timestamp":1721105451000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Preliminary results on novel adjuvant combinations suggest enhanced immunogenicity of whole inactivated pandemic influenza vaccines"],"prefix":"10.3389","volume":"4","author":[{"given":"Allegra","family":"Peletta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lie","family":"Marmy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samo","family":"Guzelj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alcidia","family":"Ramos Barros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u017diga","family":"Jakopin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerrit","family":"Borchard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,7,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1007\/978-3-540-92165-3_16","article-title":"Adjuvants for pandemic influenza vaccines","volume":"333","author":"Atmar","year":"2009","journal-title":"Vaccines Pandemic Influenza"},{"key":"B2","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1111\/j.1365-2567.2008.02960.x","article-title":"Variable antigen uptake due to different expression of the macrophage mannose receptor by dendritic cells in various inbred mouse strains","volume":"127","author":"Autenrieth","year":"2009","journal-title":"Immunology"},{"key":"B3","doi-asserted-by":"publisher","first-page":"108933","DOI":"10.1016\/j.steroids.2021.108933","article-title":"The steroidal alkaloids \u03b1-tomatine and tomatidine: panorama of their mode of action and pharmacological properties","volume":"176","author":"Bailly","year":"2021","journal-title":"Steroids"},{"key":"B4","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.jconrel.2016.06.017","article-title":"DLS and zeta potential\u2013what they are and what they are not?","volume":"235","author":"Bhattacharjee","year":"2016","journal-title":"J. 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