Monophosphoryl lipid A-adjuvanted nucleoprotein-neuraminidase nanoparticles improve immune protection against divergent influenza viruses

Wang, Ye; Dong, Chunhong; Ma, Yao; Zhu, Wandi; Gill, Harvinder Singh; Denning, Timothy L.; Kang, Sang‐Moo; Wang, Bao‐Zhong

doi:10.1016/j.nano.2022.102614

Cited by 6 publications

(6 citation statements)

References 49 publications

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“…[17,18] Our previous studies found that protein nanoparticles predominantly induced Th2-biased immune responses versus Th1 cell type. [8] Supplementing appropriate adjuvants with protein nanoparticles could improve the antigen immunogenicity and orchestrate the immune responses. Therefore, we supplemented SDAD protein nanoparticles with different adjuvant combinations and determined the maturation and cytokine secretions of bone marrow-derived dendritic cells (BMDCs) after stimulation by the SDAD nanoparticles with or without ISCOMs, ISCOMs/cGAMP, or ISCOMs/MPLA adjuvants.…”

Section: Generation and Characterization Of Sdad-crosslinked Protein ...mentioning

confidence: 99%

“…For example, we found the combination of toll-like receptor 4 (TLR4) ligand-monophosphoryl lipid A (MPLA) in double-layered NP and neuraminidase (NA) nanoparticles enhanced Th1 immune responses, as well as increased cross-protections against different influenza viral infections. [8] Besides aluminum salts, only a few adjuvants have been approved for human usage by the FDA in the past 70 years. [3] Combined adjuvant systems have been evaluated and approved for vaccine usage in humans to exploit the advantages of different adjuvants and enhance a more comprehensive immune response.…”

Section: Introductionmentioning

confidence: 99%

“…For example, we found the combination of toll‐like receptor 4 (TLR4) ligand‐ monophosphoryl lipid A (MPLA) in double‐layered NP and neuraminidase (NA) nanoparticles enhanced Th1 immune responses, as well as increased cross‐protections against different influenza viral infections. [ 8 ]…”

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: Generation and Characterization Of Sdad-crosslinked Protein ...mentioning

confidence: 99%

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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“…Toll-like receptor (TLR) agonist adjuvants have shown exceptional promise as they enhance the activation and maturation of antigen presenting cells [15][16] . For example, CpG oligodeoxynucleotide is a TLR9 agonist that has been used in commercial vaccines (e.g., Hepislav-B; Dynavax) and Monophosphoryl lipid A (MPLA) is a TLR4 agonist that has been incorporated into several commercial adjuvants (e.g., AS04, part of Fendrix and Cervarix; GlaxoSmithKline), and both have been shown to be effective as adjuvants in influenza vaccines [17][18][19] . More recently, the potent TLR7/8 agonist 3M-052 (an imidazoquinoline derivative; 3M Corporation) has demonstrated exceptional promise in enhancing humoral immunity to HIV envelope proteins as well as SARS-CoV-2 [20][21][22] .…”

Section: Introductionmentioning

confidence: 99%

Sustained vaccine exposure elicits more rapid, consistent, and broad humoral immune responses to multivalent influenza vaccines

Saouaf,

Ou,

Song

et al. 2024

Preprint

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With the ever-present threat of pandemics, it is imperative we develop vaccine technologies eliciting broad and durable immunity to high-risk pathogens. Yet, current annual influenza vaccines, for example, fail to provide robust immunity against the 3-4 homologous strains they contain, let alone heterologous strains. Herein, we demonstrate that sustained delivery of multivalent influenza vaccines from an injectable polymer-nanoparticle (PNP) hydrogel technology induces more rapid, consistent, and potent humoral immune responses against multiple homologous viruses, as well as potent responses against heterologous viruses and potential pandemic subtypes H5N1, H7N9 and H9N2. Further, admixing PNP hydrogels with commercial influenza vaccines results in stronger hemagglutination inhibition against both heterologous and homologous viruses. We show this enhanced potency and breadth arises from higher affinity antibodies targeting both the hemagglutinin stem and head. Overall, this simple and effective sustained delivery platform for multivalent annual influenza vaccines generates durable, potent, and remarkably broad immunity to influenza.

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“…To overcome this issue, previous studies have used chemical crosslinking to create protein nanoparticle vaccines that display rNAs on the surface. 39 , 40 However, the nonspecific nature of chemical crosslinking introduces inherent heterogeneity, making it challenging to achieve the consistency needed for a vaccine.…”

Section: Introductionmentioning

confidence: 99%

Capsid virus-like particle display improves recombinant influenza neuraminidase antigen stability and immunogenicity in mice

Kang,

Martinez,

Aves

et al. 2024

iScience

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Monophosphoryl lipid A-adjuvanted nucleoprotein-neuraminidase nanoparticles improve immune protection against divergent influenza viruses

Cited by 6 publications

References 49 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

Sustained vaccine exposure elicits more rapid, consistent, and broad humoral immune responses to multivalent influenza vaccines

Capsid virus-like particle display improves recombinant influenza neuraminidase antigen stability and immunogenicity in mice

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