Inhalable hybrid nanovaccines with virus-biomimetic structure boost protective immune responses against SARS-CoV-2 variants

• Published in: Journal of nanobiotechnology Vol. 22; no. 1; p. 76
• Main Authors: Wang, Shuqi, Ding, Peiyang, Shen, Lingli, Fan, Daopeng, Cheng, Hanghang, Huo, Jian, Wei, Xin, He, Hua, Zhang, Gaiping
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 27.02.2024; BioMed Central; BMC
• Subjects: Alveoli; Animals; Antibodies, Neutralizing; Antibodies, Viral; Antigen presentation; Antigenic variation; B cells; Biomimetics; Broad-spectrum neutralization activity; Cell activation; Coronaviruses; COVID-19; COVID-19 - prevention & control; COVID-19 vaccines; Disease transmission; Enzymes; Genetic engineering; Genetically engineered nanovesicles; Genetically modified organisms; Health aspects; Humans; Immune response; Immunity; Immunity, Mucosal; Immunization; Immunoglobulin A; Immunoglobulin G; Infectious diseases; Influenza; Influenza vaccines; Inhalable hybrid nanovaccine; Intranasal medication; Lipids; Lymphocytes B; Macrophages; Methods; Mice; Mucosal immunity; Nanomedicine; Nanovaccines; Neutralization; NF-κB protein; Particle size; Protective structures; Proteins; Public health; Respiratory diseases; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Side effects; Signal transduction; Surface active agents; Surfactants; T cells; TLR4 protein; Toll-like receptors; Vaccination; Vaccines; Viral diseases; Virus-biomimetic structure; Viruses; China; SARS-CoV-2; Virus-biomimetic structure; Genetically engineered nanovesicles; Mucosal immunity; Broad-spectrum neutralization activity; Inhalable hybrid nanovaccine
• ISSN: 1477-3155; 1477-3155
• DOI: 10.1186/s12951-024-02345-3

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with different antigenic variants, has posed a significant threat to public health. It is urgent to develop inhalable vaccines, instead of injectable vaccines, to elicit mucosal immunity against respiratory viral infections. We reported an inhalable hybrid nanovaccine (NV -MLipo) to boost protective immunity against SARS-CoV-2 infection. Nanovesicles derived from genetically engineered 293T cells expressing RBD (NV ) were fused with pulmonary surfactant (PS)-biomimetic liposomes containing MPLA (MLipo) to yield NV -MLipo, which possessed virus-biomimetic structure, inherited RBD expression and versatile properties. In contrast to subcutaneous vaccination, NV -MLipo, via inhalable vaccination, could efficiently enter the alveolar macrophages (AMs) to elicit AMs activation through MPLA-activated TLR4/NF-κB signaling pathway. Moreover, NV -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 -MLipo also demonstrated broad-spectrum neutralization activity against SARS-CoV-2 (WT, Delta, Omicron) pseudovirus, and protected immunized mice against WT pseudovirus infection. This inhalable NV -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.