Layered protein nanoparticles containing influenza B HA stalk induced sustained cross-protection against viruses spanning both viral lineages

Song, Yufeng; Zhu, Wandi; Wang, Ye; Deng, Lei; Ma, Yao; Dong, Chunhong; Gonzalez, Gilbert X.; Kim, Joo; Wei, Lai; Kang, Sang‐Moo; Wang, Bao‐Zhong

doi:10.1016/j.biomaterials.2022.121664

Cited by 4 publications

(8 citation statements)

References 77 publications

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“…This finding indicated that ISCOMs/MPLA might further stimulate substantial DC maturation and cytokine secretion to help the protein nanoparticle uptake and antigen presentation by APCs, as we have seen that DCs could efficiently internalize the protein nanoparticles in previous studies. [7,57] The influence of IS-COMs/MPLA on the retention, internalization, and translocation of antigens by immune cells on mucosal surfaces will be further determined.…”

Section: Discussionmentioning

confidence: 99%

“…[4][5][6] The nanoparticles fabricated using influenza B virus-derived nucleoprotein (NP) and HA stalk displayed cross-protection against influenza B viruses from two lineages. [7] The fabrication of our previous protein nanoparticles is based on homo-bifunctional DTSSP (3,3′dithiobis(sulfosuccinimidyl propionate))crosslinking, more controlled and efficient fabrication methods are worth investigating to improve the nanoparticle formulations. In addition, combining appropriate adjuvants with protein nanoparticle vaccines will be a convenient way to further increase immune responses and protective effectiveness.…”

Section: Introductionmentioning

confidence: 99%

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

Zhu

Park

Pho

et al. 2023

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Zhu

Park

Pho

et al. 2023

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“…Stabilizing the HA stem in the trimeric state and pre-fusion conformation favors the formation of native antigenicity. In previous research, the trimeric state of the recombinant HA stem was stabilized by fusing an exogenous trimerization motif to the HA stem polypeptide [ 12 , 23 , 29 , 30 ]. However, in our study, we found that the intact H1 transmembrane domain could assist in immobilizing H1 stem trimerization on the VLP surface; on the other hand, the intact fusion peptide limits the H1 stem to the pre-fusion state.…”

Section: Discussionmentioning

confidence: 99%

Chimeric Virus-like Particles Co-Displaying Hemagglutinin Stem and the C-Terminal Fragment of DnaK Confer Heterologous Influenza Protection in Mice

Liu

Yue

et al. 2022

Viruses

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Influenza virus hemagglutinin (HA) stem is currently regarded as an extremely promising immunogen for designing universal influenza vaccines. The appropriate antigen-presenting vaccine vector would be conducive to increasing the immunogenicity of the HA stem antigen. In this study, we generated chimeric virus-like particles (cVLPs) co-displaying the truncated C-terminal of DnaK from Escherichia coli and H1 stem or full-length H1 antigen using the baculovirus expression system. Transmission electronic micrography revealed the expression and presentation of H1 stem antigens on the surface of VLPs. Vaccinations of mice with the H1 stem cVLPs induced H1-specific immune responses and provided heterologous immune protection in vivo, which was more effective than vaccinations with VLPs displaying H1 stem alone in protecting mice against weight loss as well as increasing survival rates after lethal influenza viral challenge. The results indicate that the incorporation of the truncated C-terminal of DnaK as an adjuvant protein into the cVLPs significantly enhances the H1-specific immunity and immune protection. We have explicitly identified the VLP platform as an effective way of expressing HA stem antigen and revealed that chimeric VLP is an vaccine vector for developing HA stem-based universal influenza vaccines.

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“…Song et al also used DTSSP crosslinkers to synthesize an influenza vaccine nanoparticle from influenza B NP and HA stalk. [ 70 ] The nanoparticles were formed via desolvation of soluble NP and coated with HA stalk using DTSSP. Upon intranasal vaccination, a significant increase in the population of IL‐4 and IFN‐γ secreting T cells was seen in mice administered DTSSP crosslinked nanoparticles compared to soluble antigens.…”

Section: Chemical Crosslinkersmentioning

confidence: 99%

“…[ 65 ] 3,3 0dithiobis(sulfosuccinimidyl propionate) (DTSSP) is one of the commonly utilized crosslinkers for direct conjugation of antigens to fabricate protein nanoparticles, especially for the development of influenza vaccines. [66][67][68][69][70][71][72] DTSSP contains two NHS-ester reactive groups, which react with terminal and lysine amines, with a disulfide bond between an 8-carbon spacer arm. For the synthesis of influenza vaccine nanoparticles, DTSSP crosslinkers were used to stabilize nanoparticles formed by adding desolvating agents to proteins such as M2e or nucleoprotein (NP) as shown in Figure 6.…”

Section: Chemical Crosslinkersmentioning

confidence: 99%

Chemical and biological conjugation strategies for the development of multivalent protein vaccine nanoparticles

2023

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The development of subunit vaccine platforms has been of considerable interest due to their good safety profile and ability to be adapted to new antigens, compared to other vaccine typess. Nevertheless, subunit vaccines often lack sufficient immunogenicity to fully protect against infectious diseases. A wide variety of subunit vaccines have been developed to enhance antigen immunogenicity by increasing antigen multivalency, as well as stability and delivery properties, via presentation of antigens on protein nanoparticles. Increasing multivalency can be an effective approach to provide a potent humoral immune response by more strongly engaging and clustering B cell receptors (BCRs) to induce activation, as well as increased uptake by antigen presenting cells and their subsequent T cell activation. Proper orientation of antigen on protein nanoparticles is also considered a crucial factor for enhanced BCR engagement and subsequent immune responses. Therefore, various strategies have been reported to decorate highly repetitive surfaces of protein nanoparticle scaffolds with multiple copies of antigens, arrange antigens in proper orientation, or combinations thereof. In this review, we describe different chemical bioconjugation methods, approaches for genetic fusion of recombinant antigens, biological affinity tags, and enzymatic conjugation methods to effectively present antigens on the surface of protein nanoparticle vaccine scaffolds.

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Layered protein nanoparticles containing influenza B HA stalk induced sustained cross-protection against viruses spanning both viral lineages

Cited by 4 publications

References 77 publications

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

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

Chimeric Virus-like Particles Co-Displaying Hemagglutinin Stem and the C-Terminal Fragment of DnaK Confer Heterologous Influenza Protection in Mice

Chemical and biological conjugation strategies for the development of multivalent protein vaccine nanoparticles

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