A recombinant protein containing influenza viral conserved epitopes and superantigen induces broad-spectrum protection

Li, Yansheng; Xu, Mingkai; Li, Yongqiang; Gu, Weizhong; Halimu, Gulinare; Li, Yuqi; Zhang, Zhichun; Zhou, Libao; Liao, Hui; Yao, Songyuan; Zhang, Huiwen; Zhang, Chenggang

doi:10.7554/elife.71725

Cited by 2 publications

(1 citation statement)

References 42 publications

(41 reference statements)

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“…The faster recovery and limited weight loss of VSV*∆G(NP) vaccinated mice is characteristic for non-sterile immunity, often attributed to T cell immunity. As NP can be a strong driver of T cell immunity, we first hypothesized that the protection in our immunization-challenge model is based on cellular immunity 22,82,83,[83][84][85] . However, we detected only limited increases in IFNγ, and no increase in IL-4 secreting T cells after immunization with our various VSV replicons.…”

Section: Protection Against Heterologous Iav Challenge After Vsv Repl...mentioning

confidence: 99%

Non-neutralizing antibody responses to vesicular stomatitis virus-vectored influenza A virus vaccines correlate with protection

Wittwer

Zimmer²,

Rommel

et al. 2022

Preprint

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Seasonal influenza virus infections remain a major global public health burden. In addition, influenza A virus (IAV) exhibits high pandemic potential through zoonotic spread from avian hosts to humans. Currently licensed IAV vaccines are mainly directed against the immuno-dominant surface protein hemagglutinin (HA). Since HA is antigenically highly variable, IAV can escape vaccine-derived immunity through antigenic drift. However, vaccine preparations such as the live-attenuated influenza vaccine (LAIV) also contain other more conserved viral antigens, whose contribution to influenza immunity are not fully elucidated. To determine the extent to which conserved LAIV antigens contribute to establishing protective immunity against heterologous IAV strains, we generated vesicular stomatitis virus-based single-round vector vaccines expressing individual LAIV antigens, and tested their ability to protect mice from a heterologous challenge with two IAV strains, PR8[H1N1] and rSC35M[H7N7]. We found that immunization with nucleoprotein (NP), ion channel M2, and the stem-region of HA (HAstem), but not matrix protein (M1), provide protection from severe disease caused by either IAV strain. This effect correlated with development of non-neutralizing antibodies cross-reactive with both virus strains. Notably, the individual antigens induced specific IgG subclass profiles with different reactivity against PR8 and rSC35M. Sera from vaccinated animals activated Fc-gamma receptor IV-mediated effector functions, suggesting that they can induce cell-mediated immune defense mechanisms, such as antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis. Combination of the most potent antigens NP and M2 in a mixed vaccination resulted in enhanced protection against IAV challenge, suggesting that the antibody responses against these antigens were synergistic. Our results demonstrate the potency of NP and M2 proteins to serve as conserved antigen targets, resulting in broad protection against severe IAV disease.

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Section: Protection Against Heterologous Iav Challenge After Vsv Repl...mentioning

confidence: 99%

Non-neutralizing antibody responses to vesicular stomatitis virus-vectored influenza A virus vaccines correlate with protection

Wittwer

Zimmer²,

Rommel

et al. 2022

Preprint

View full text Add to dashboard Cite

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Flagellin-Fused Protein Targeting M2e and HA2 Induces Innate and T-Cell Responses in Mice of Different Genetic Lines

et al. 2022

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Efficient control of influenza A infection can potentially be achieved through the development of broad-spectrum vaccines. Recombinant proteins incorporating conserved influenza A virus peptides are one of the platforms for the development of cross-protective influenza vaccines. We constructed a recombinant protein Flg-HA2-2-4M2ehs, in which the extracellular domain of the M2 protein (M2e) and the sequence (aa76-130) of the second subunit of HA (HA2) were used as target antigens. In this study, we investigated the ability of the Flg-HA2-2-4M2ehs protein to activate innate immunity and stimulate the formation of T-cell response in mice of different genetic lines after intranasal immunization. Our studies showed that the Flg-HA2-2-4M2ehs protein was manifested in an increase in the relative content of neutrophils, monocytes, and interstitial macrophages, against the backdrop of a decrease in the level of dendritic cells and increased expression in the CD86 marker. In the lungs of BALB/c mice, immunization with the Flg-HA2-2-4M2ehs protein induced the formation of antigen-specific CD4+ and CD8+ effector memory T cells, producing TNF-α. In mice C57Bl/6, the formation of antigen-specific effector CD8+ T cells, predominantly producing IFN-γ+, was demonstrated. The data obtained showed the formation of CD8+ and CD4+ effector memory T cells expressing the CD107a.

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A recombinant protein containing influenza viral conserved epitopes and superantigen induces broad-spectrum protection

Cited by 2 publications

References 42 publications

Non-neutralizing antibody responses to vesicular stomatitis virus-vectored influenza A virus vaccines correlate with protection

Non-neutralizing antibody responses to vesicular stomatitis virus-vectored influenza A virus vaccines correlate with protection

Flagellin-Fused Protein Targeting M2e and HA2 Induces Innate and T-Cell Responses in Mice of Different Genetic Lines

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