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It is urgent to develop inhalable vaccines, instead of injectable vaccines, to elicit mucosal immunity against respiratory viral infections.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We reported an inhalable hybrid nanovaccine (NV\n                      <jats:sub>RBD<\/jats:sub>\n                      -MLipo) to boost protective immunity against SARS-CoV-2 infection. Nanovesicles derived from genetically engineered 293T cells expressing RBD (NV\n                      <jats:sub>RBD<\/jats:sub>\n                      ) were fused with pulmonary surfactant (PS)-biomimetic liposomes containing MPLA (MLipo) to yield NV\n                      <jats:sub>RBD<\/jats:sub>\n                      -MLipo, which possessed virus-biomimetic structure, inherited RBD expression and versatile properties.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In contrast to subcutaneous vaccination, NV\n                      <jats:sub>RBD<\/jats:sub>\n                      -MLipo, via inhalable vaccination, could efficiently enter the alveolar macrophages (AMs) to elicit AMs activation through MPLA-activated TLR4\/NF-\u03baB signaling pathway. Moreover, NV\n                      <jats:sub>RBD<\/jats:sub>\n                      -MLipo induced T and B cells activation, and high level of RBD-specific IgG and secretory IgA (sIgA), thus elevating protective mucosal and systemic immune responses, while reducing side effects. NV\n                      <jats:sub>RBD<\/jats:sub>\n                      -MLipo also demonstrated broad-spectrum neutralization activity against SARS-CoV-2 (WT, Delta, Omicron) pseudovirus, and protected immunized mice against WT pseudovirus infection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This inhalable NV\n                      <jats:sub>RBD<\/jats:sub>\n                      -MLipo, as an effective and safe nanovaccine, holds huge potential to provoke robust mucosal immunity, and might be a promising vaccine candidate to combat respiratory infectious diseases, including COVID-19 and influenza.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12951-024-02345-3","type":"journal-article","created":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T00:02:03Z","timestamp":1708992123000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Inhalable hybrid nanovaccines with virus-biomimetic structure boost protective immune responses against SARS-CoV-2 variants"],"prefix":"10.1186","volume":"22","author":[{"given":"Shuqi","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiyang","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingli","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daopeng","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanghang","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Huo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaiping","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,27]]},"reference":[{"key":"2345_CR1","doi-asserted-by":"publisher","first-page":"136143","DOI":"10.1016\/j.cej.2022.136143","volume":"442","author":"B Kang","year":"2022","unstructured":"Kang B, Lee Y, Lim J, Yong D, Ki Choi Y, Woo Yoon S, Seo S, Jang S, Uk Son S, Kang T, et al. 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