Broadly Protective Neuraminidase-Based Influenza Vaccines and Monoclonal Antibodies: Target Epitopes and Mechanisms of Action

Abbadi, Nada; Mousa, Jarrod J.

doi:10.3390/v15010200

Cited by 4 publications

(4 citation statements)

References 101 publications

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“…Non-neutralizing anti-viral antibodies prevent the function of envelope proteins required for spreading infection. For example, antibodies targeting the influenza A virus envelope protein neuraminidase limit infection because they can inhibit the enzymatic activity of neuraminidase, which is required for the virus to leave infected cells [21,22].…”

Section: Discussionmentioning

confidence: 99%

Analysis of Virus-Specific B Cell Epitopes Reveals Extensive Antigen Degradation Prior to Recognition

Ras-Carmona,

Reche

2024

Cells

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B cell epitopes must be visible for recognition by cognate B cells and/or antibodies. Here, we studied that premise for known linear B cell epitopes that were collected from the Immune Epitope Database as being recognized by humans during microbial infections. We found that the majority of such known B cell epitopes are virus-specific linear B cell epitopes (87.96%), and most are located in antigens that remain enclosed in host cells and/or virus particles, preventing antibody recognition (18,832 out of 29,225 epitopes). Moreover, we estimated that only a minority (32.72%) of the virus-specific linear B cell epitopes that are found in exposed viral regions (e.g., the ectodomains of envelope proteins) are solvent accessible on intact antigens. Hence, we conclude that ample degradation/processing of viral particles and/or infected cells must occur prior to B cell recognition, thus shaping the B cell epitope repertoire.

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Section: Discussionmentioning

confidence: 99%

Analysis of Virus-Specific B Cell Epitopes Reveals Extensive Antigen Degradation Prior to Recognition

Ras-Carmona,

Reche

2024

Cells

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“…Non-neutralizing anti-viral antibodies prevent the function of envelope proteins required for spreading infection. For example, antibodies targeting influenza A virus envelope protein neuraminidase limit infection because they can inhibit the enzymatic activity of neuraminidase, which is required by the virus to leave infected cells (13, 14). Interestingly, a substantial number of B cell epitopes in envelope proteins map outside of the ectodomain (6.68 %), the protein region visible to antibody recognition (Figure 3A).…”

Section: Discussionmentioning

confidence: 99%

Section: B Cell Receptors and Antibodies Can Only Recognize Visible A...mentioning

confidence: 99%

Analysis of virus-specific B cell epitopes reveals extensive antigen processing prior to recognition

Ras-Carmona,

Reche

2023

Preprint

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B cell epitopes must be solvent accessible for recognition by cognate B cells and antibodies. Here, we sought to study such premise for B cell epitopes targeted during infection in humans, available at the Immune Epitope Database. Most of these B cell epitopes were virus-specific linear B cell epitopes and so we focused on them, analyzing first the localization of the relevant antigens. Antigen localization could be unequivocally assigned to 26498 linear B cell epitopes. Of those, 18832 B cell epitopes belonged to antigens that remain enclosed in host cells and/or virus particles, hidden to antibody recognition, while just 7666 lie in ectodomains of viral envelope antigens and/or mature secreted antigens, visible to antibody recognition. Next, we selected B cell epitopes that mapped in antigens with known tertiary (3D-)structures and determined residue relative solvent accessibility (rRSA), comparing them with those of conformational B cell epitopes obtained from available 3D-structures of antigen-antibody complexes. rRSA values computed form linear B cell epitopes had a median value of 23.00%, while that of conformational B cell epitopes was 48.50%. Moreover, considering average rRSA values per entire epitopes (eRSA), only 32.72% of the linear B cell epitopes had eRSA values minimally comparable to those of conformational B cell epitopes. In sum, our results point that most virus-specific B cell epitopes targeted during infection are unreachable to antibody recognition on intact viral particles and/or host cells. Hence, we must conclude that antigen recognition by antibodies must be preceded by degradation/processing of viral particles and infected cells.

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“…The newly synthesized vRNPs and progeny virions are then assembled near the cell membrane, priming them for bud formation. NA aids in the release of these progeny virions by cleaving the sialic acid of membrane glycoproteins [ 7 ]. Beyond facilitating the release and dissemination of progeny virions, the NA protein of IAV also performs the crucial functions of increasing virion infectivity and assisting in HA-mediated membrane fusion [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Novel Anti-Viral Properties of the Herbal Extract of Davallia mariesii against Influenza A Virus

Chen,

Chao,

Hsieh

et al. 2024

Viruses

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Gu-Sui-Bu, the dried rhizome of Davallia mariesii, is a traditional Chinese herbal remedy with a significant history of treating osteoporosis and inflammatory conditions. However, its potential as an anti-influenza agent and its underlying mechanisms of action remain unexplored. To obtain a more potent extract from D. mariesii and gain insights into its mechanism of action against influenza A virus (IAV), we utilized a partitioning process involving organic solvents and water, resulting in the isolation of butanolic subfractions of the D. mariesii extract (DMBE). DMBE exhibited a broad anti-viral spectrum, effectively inhibiting IAV, with an EC50 of 24.32 ± 6.19 µg/mL and a selectivity index of 6.05. We subsequently conducted a series of in vitro assays to evaluate the antiviral effects of DMBE and to uncover its mechanisms of action. DMBE was found to inhibit IAV during the early stages of infection by hindering the attachment of the virus onto and its penetration into host cells. Importantly, DMBE was observed to hinder IAV-mediated cell–cell fusion. It also inhibited neuraminidase activity, plaque size, and the expression levels of phospho-AKT. In summary, this study provides evidence for the effectiveness of D. mariesii as a complementary and alternative herbal remedy against IAV. Specifically, our data highlight DMBE’s capabilities in inhibiting viral entry and the release of virions.

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Broadly Protective Neuraminidase-Based Influenza Vaccines and Monoclonal Antibodies: Target Epitopes and Mechanisms of Action

Cited by 4 publications

References 101 publications

Analysis of Virus-Specific B Cell Epitopes Reveals Extensive Antigen Degradation Prior to Recognition

Analysis of Virus-Specific B Cell Epitopes Reveals Extensive Antigen Degradation Prior to Recognition

Analysis of virus-specific B cell epitopes reveals extensive antigen processing prior to recognition

Novel Anti-Viral Properties of the Herbal Extract of Davallia mariesii against Influenza A Virus

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