Nanoparticles based on artificial self-assembling peptide and displaying M2e peptide and stalk HA epitopes of influenza A virus induce potent humoral and T-cell responses and protect against the viral infection

Zykova, A.; Blokhina, Elena; Степанова, Л. А.; Shuklina, Marina A.; Цыбалова, Л. М.; Kuprianov, Victor V.; Ravin, Nikolai V.

doi:10.1016/j.nano.2021.102463

Cited by 13 publications

(19 citation statements)

References 36 publications

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“…While central memory skewing is observed in CD8 + T cells and effector memory skewing is observed in CD4 + T cells in the resting state, both the CD4 + and CD8 + T-cell subsets are predominantly of the effector memory phenotype in the peripheral organs [ 52 , 53 , 54 , 55 , 56 ]. Consistent with previous reports showing that nanoparticles are helpful in inducing CD4+ effector memory T cells, the addition of LNP carriers was helpful in elevating gE-specific CD4+ effector memory T cell levels compared with the combination of CpG and QS21 alone in our results [ 57 , 58 ].…”

Section: Discussionsupporting

confidence: 93%

Ionizable Lipid Nanoparticles Enhanced the Synergistic Adjuvant Effect of CpG ODNs and QS21 in a Varicella Zoster Virus Glycoprotein E Subunit Vaccine

et al. 2022

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Varicella zoster virus (VZV) causes two diseases: varicella upon primary infection and herpes zoster when latent viruses in the sensory ganglia reactivate. While varicella vaccines depend on humoral immunity to prevent VZV infection, cell-mediated immunity (CMI), which plays a therapeutic role in the control or elimination of reactivated VZV in infected cells, is decisive for zoster vaccine efficacy. As one of the most abundant glycoproteins of VZV, conserved glycoprotein E (gE) is essential for viral replication and transmission between ganglion cells, thus making it an ideal target subunit vaccine antigen; gE has been successfully used in the herpes zoster vaccine ShingrixTM on the market. In this report, we found that ionizable lipid nanoparticles (LNPs) approved by the Food and Drug Administration (FDA) as vectors for coronavirus disease 2019 (COVID-19) mRNA vaccines could enhance the synergistic adjuvant effect of CpG oligodeoxynucleotides (CpG ODNs) and QS21 on VZV-gE, affecting both humoral immunity and CMI. Vaccines made with these LNPs showed promise as varicella vaccines without a potential risk of herpes zoster, which identifies them as a novel type of herpes zoster vaccine similar to ShingrixTM. All of the components in this LNP-CpG-QS21 adjuvant system were proven to be safe after mass vaccination, and the high proportion of cholesterol contained in the LNPs was helpful for limiting the cytotoxicity induced by QS21, which may lead to the development of a novel herpes zoster subunit vaccine for clinical application.

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Section: Discussionsupporting

confidence: 93%

Ionizable Lipid Nanoparticles Enhanced the Synergistic Adjuvant Effect of CpG ODNs and QS21 in a Varicella Zoster Virus Glycoprotein E Subunit Vaccine

et al. 2022

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“…Furthermore, one HA conjugated ferritin vaccine has completed phase 1 clinical trial. Another ferritin-based influenza H1 vaccines starts to recruit human volunteers [43].…”

Section: Discussionmentioning

confidence: 99%

“…NPs can accelerate innate and adaptive responses by mimicking pathogen-associated molecular patterns. Previous reports have revealed that ferritin NPs can efficiently drain to lymph nodes, and are easily captured by dendritic cells (DCs) and macrophages [41,43]. Moreover, it is reported that ferritin NPs can induce bone marrow-derived DC maturation, which facilitates T-cell proliferation and differentiation into Th1 and Th2 [46].…”

Section: Discussionmentioning

confidence: 99%

A biepitope, adjuvant-free, self-assembled influenza nanovaccine provides cross-protection against H3N2 and H1N1 viruses in mice

et al. 2022

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Currently, the incorporation of multiple epitopes into vaccines is more desirable than the incorporation of a single antigen for universal influenza vaccine development. However, epitopes induce poor immune responses. Although the use of adjuvants can overcome this obstacle, it may raise new problems. Effective antigen delivery vehicles that can function as both antigen carriers and intrinsic adjuvants are highly desired for vaccine development. Here, we report a biepitope nanovaccine that provides complete protection in mice against H3N2 virus as well as partial protection against H1N1 virus. This vaccine (3MCD-f) consists of two conserved epitopes (matrix protein 2 ectodomain (M2e) and CDhelix), and these epitopes were presented on the surface of ferritin in a sequential tandem format. Subcutaneous immunization with 3MCD-f in the absence of adjuvant induces robust humoral and cellular immune responses. These results provide a proof of concept for the 3MCD-f nanovaccine that might be an ideal candidate for future influenza pandemics.

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“…Combining conserved antigens with polyvalency, possibly including internal viral protein antigens, is an avenue to improved protection via both humoral and cellular immunity [61][62][63]. Multivalent immunization using the mRNA format has been shown to confer broad cross-protection in mice even at low doses [64].…”

Section: Opportunities Offered By Mrnamentioning

confidence: 99%

Message in a bottle: mRNA vaccination for influenza

Shartouny

2022

Journal of General Virology

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Current influenza vaccines, while being the best method of managing viral outbreaks, have several major drawbacks that prevent them from being wholly-effective. They need to be updated regularly and require extensive resources to develop. When considering alternatives, the recent deployment of mRNA vaccines for SARS-CoV-2 has created a unique opportunity to evaluate a new platform for seasonal and pandemic influenza vaccines. The mRNA format has previously been examined for application to influenza and promising data suggest it may be a viable format for next-generation influenza vaccines. Here, we discuss the prospect of shifting global influenza vaccination efforts to an mRNA-based system that might allow better control over the product and immune responses and could aid in the development of a universal vaccine.

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Nanoparticles based on artificial self-assembling peptide and displaying M2e peptide and stalk HA epitopes of influenza A virus induce potent humoral and T-cell responses and protect against the viral infection

Cited by 13 publications

References 36 publications

Ionizable Lipid Nanoparticles Enhanced the Synergistic Adjuvant Effect of CpG ODNs and QS21 in a Varicella Zoster Virus Glycoprotein E Subunit Vaccine

Ionizable Lipid Nanoparticles Enhanced the Synergistic Adjuvant Effect of CpG ODNs and QS21 in a Varicella Zoster Virus Glycoprotein E Subunit Vaccine

A biepitope, adjuvant-free, self-assembled influenza nanovaccine provides cross-protection against H3N2 and H1N1 viruses in mice

Message in a bottle: mRNA vaccination for influenza

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