ISCOMs/MPLA‐Adjuvanted SDAD Protein Nanoparticles Induce Improved Mucosal Immune Responses and Cross‐Protection in Mice

Abstract

The epidemics caused by the influenza virus are a serious threat to public health and the economy. Adding appropriate adjuvants to improve immunogenicity and finding effective mucosal vaccines to combat respiratory infection at the portal of virus entry are important strategies to boost protection. In this study, a novel type of core/shell protein nanoparticle consisting of influenza nucleoprotein (NP) as the core and NA1‐M2e or NA2‐M2e fusion proteins as the coating antigens by SDAD hetero‐bifunctional crosslinking is exploited. Immune‐stimulating complexes (ISCOMs)/monophosphoryl lipid A (MPLA) adjuvants further boost the NP/NA‐M2e SDAD protein nanoparticle‐induced immune responses when administered intramuscularly. The ISCOMs/MPLA‐adjuvanted protein nanoparticles are delivered through the intranasal route to validate the application as mucosal vaccines. ISCOMs/MPLA‐adjuvanted nanoparticles induce significantly strengthened antigen‐specific antibody responses, cytokine‐secreting splenocytes in the systemic compartment, and higher levels of antigen‐specific IgA and IgG in the local mucosa. Meanwhile, significantly expanded lung resident memory (RM) T and B cells (TRM/BRM) and alveolar macrophages population are observed in ISCOMs/MPLA‐adjuvanted nanoparticle‐immunized mice with a 100% survival rate after homogeneous and heterogeneous H3N2 viral challenges. Taken together, ISCOMs/MPLA‐adjuvanted protein nanoparticles could improve strong systemic and mucosal immune responses conferring protection in different immunization routes.

Development of Self-Assembled Protein Nanocage Spatially Functionalized with HA Stalk as a Broadly Cross-Reactive Influenza Vaccine Platform

“…Furthermore, M2e exhibits weaker immunogenicity than HA. It is therefore recommended to use M2e antigens together with other antigens. ,,, Of note, recent findings highlight the significance of T cell responses for broadly cross-reactive immunity against influenza. − Broadly cross-reactive T cell responses were shown to be potent and significantly contribute to broad protection against influenza infections which was independently of hemagglutination inhibition (HAI) titer, a major indicator of neutralizing HA-specific humoral immunity …”

The quest for nanoparticle-powered vaccines in cancer immunotherapy

“…Immunostimulatin complexes (ISCOMs) are a popular form of nanovaccines in vaccine research [113,[316][317][318]. ISCOMs are cage-like particles, typically 40-50 nm, that spontaneously form from phospholipids, cholesterol, saponin, and protein antigens [319][320][321].…”

“…Based on these findings, ISCOMs and ISCOMATRIX ™ have great potential as adjuvants in the development of cancer vaccines [320]. As a whole, nanovaccines such as ISCOMs are popular in vaccine research [316,333]. They have high stability, less toxicity, and strong adjuvant properties [336,337].…”

Dual-Antigen Subunit Vaccine Nanoparticles for Scrub Typhus

“…The subunit vaccine NPs were formed via desolvation, and to augment the neutralizing activity of antibodies, the desolvated NPs were layered with an additional coating of the r56 antigen. Reducible 3,3 -dithiobis(sulfosuccinimidyl propionate) (DTSSP) and succinimidyl 2-((4,4 -azipentanamido)ethyl)-1,3 -dithiopropionate (SDAD) were exploited to stabilize and coat the subunit NPs with the r56 antigen, respectively, due to their biocompatibility and successful application for the development of vaccine NPs against influenza [41][42][43]. We hypothesized that the subunit NPs would improve both antibody and cellular immune responses, as we previously demonstrated greater immunogenicity of coated desolvated influenza antigen NPs compared to soluble antigens [41,44,45].…”