Identification of immunodominant CD8 epitope in the stalk domain of influenza B viral hemagglutinin

Muralidharan, Abenaya; Gravel, Caroline; Duran, Amparo; Larocque, Louise; Li, Changgui; Zetner, Adrian; Domselaar, Gary Van; Wang, Lisheng; Li, Xuguang

doi:10.1016/j.bbrc.2018.05.148

Cited by 6 publications

(6 citation statements)

References 34 publications

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“…Our characterization of the two truncated forms of the vaccine yielded additional interesting findings. Consistent with our recent immunoinformatics analyses (Muralidharan et al, 2018), deletion of either the N-terminus or transmembrane domain reduced the vaccine efficacy by 30% and 20%, respectively (Figure 5). The partial reduction instead of a complete abolition of protection by the two truncated vaccines is not surprising, as the vaccine-induced protective immunity does not depend on neutralizing antibodies of which the potency could be drastically reduced or even abolished if a few key amino acids are mutated or substituted.…”

Section: Discussionsupporting

confidence: 90%

“…The N-terminus of the HA2 contains the only universally conserved linear sequence (fusion peptide) (Chun et al, 2008) and is indispensable for virus entry (Skehel and Wiley, 2000). The transmembrane domain is not only indispensable for the IBV virus but also has high immunogenicity (Muralidharan et al, 2018;Zhang et al, 2017). These two truncated vaccines, designated as rAd-HA2DN30F and rAd-HA2DTMF, respectively, were compared head-to-head with the full-length rAd-HA2F.…”

Section: Immunization With Truncated Ha2 Vaccines Reduces Efficacymentioning

confidence: 99%

“…We next investigated antigen-specific cytokine levels following vaccination by the three vaccines. To this end, splenocytes from vaccinated animals were stimulated with peptides identified to be immunogenic for the quantitation of cytokines (Muralidharan et al, 2018). Specifically, P1 (FFGAIAGFL), located in the fusion peptide, was used to stimulate the splenocytes from animals vaccinated with rAd-HA2DN30F, in comparison with the full-length rAd-HA2F, to assess the role of the fusion peptide in one set of experiments.…”

Section: Truncated Forms Of the Vaccine Induce Altered Cytokine Profilesmentioning

confidence: 99%

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Synthetic vaccine affords full protection to mice against lethal challenge of influenza B virus of both genetic lineages

et al. 2021

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Section: Discussionsupporting

confidence: 90%

Section: Immunization With Truncated Ha2 Vaccines Reduces Efficacymentioning

confidence: 99%

Section: Truncated Forms Of the Vaccine Induce Altered Cytokine Profilesmentioning

confidence: 99%

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Synthetic vaccine affords full protection to mice against lethal challenge of influenza B virus of both genetic lineages

et al. 2021

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“…The potential for VLP-based vaccines to induce CD8 + T cells has been demonstrated in mice 18 and studies are on-going to determine whether or not similar responses can be elicited in humans. Although conserved T cell epitopes from influenza core proteins have attracted the most attention to date, 3,70 several human CD8 + epitopes have been identified in the HA proteins of both seasonal and avian influenza strains 76,77 and our data suggest that many more may exist. A non-living vaccine that can induce strong antibody production as well as both CD4 + and CD8 + T cell responses might provide an added layer of protection against serious influenza virus infections compared to antibodies alone.…”

Section: Discussionmentioning

confidence: 65%

Plant-derived virus-like particle vaccines drive cross-presentation of influenza A hemagglutinin peptides by human monocyte-derived macrophages

et al. 2019

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A growing body of evidence supports the importance of T cell responses to protect against severe influenza, promote viral clearance, and ensure long-term immunity. Plant-derived virus-like particle (VLP) vaccines bearing influenza hemagglutinin (HA) have been shown to elicit strong humoral and CD4 + T cell responses in both pre-clinical and clinical studies. To better understand the immunogenicity of these vaccines, we tracked the intracellular fate of a model HA (A/California/07/2009 H1N1) in human monocyte-derived macrophages (MDMs) following delivery either as VLPs (H1-VLP) or in soluble form. Compared to exposure to soluble HA, pulsing with VLPs resulted in ~3-fold greater intracellular accumulation of HA at 15 min that was driven by clathrin-mediated and clathrin-independent endocytosis as well as macropinocytosis/phagocytosis. At 45 min, soluble HA had largely disappeared suggesting its handling primarily by high-degradative endosomal pathways. Although the overall fluorescence intensity/cell had declined 25% at 45 min after H1-VLP exposure, the endosomal distribution pattern and degree of aggregation suggested that HA delivered by VLP had entered both high-degradative late and low-degradative static early and/or recycling endosomal pathways. At 45 min in the cells pulsed with VLPs, HA was strongly co-localized with Rab5, Rab7, Rab11, MHC II, and MHC I. High-resolution tandem mass spectrometry identified 115 HA-derived peptides associated with MHC I in the H1-VLP-treated MDMs. These data suggest that HA delivery to antigen-presenting cells on plant-derived VLPs facilitates antigen uptake, endosomal processing, and cross-presentation. These observations may help to explain the broad and cross-reactive immune responses generated by these vaccines.

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“…However, only the NP 30-38 peptide was able to induce interferon gamma production from FLUBV-specific polyclonal CTLs [104]. It is assumed that CTL responses against FLUBV are preferentially directed against HLA-B8 epitopes [112]. The above HLAs are common in the human population; this suggests that NP T-cell epitopes are expected to be recognized by a majority of individuals owing to the high prevalence of this allele globally.…”

Section: Conserved Protein Epitopes As Target Antigens For the Develo...mentioning

confidence: 99%

Influenza B: Prospects for the Development of Cross-Protective Vaccines

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Ramsay

et al. 2022

Viruses

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In this review, we analyze the epidemiological and ecological features of influenza B, one of the most common and severe respiratory infections. The review presents various strategies for cross-protective influenza B vaccine development, including recombinant viruses, virus-like particles, and recombinant proteins. We provide an overview of viral proteins as cross-protective vaccine targets, along with other updated broadly protective vaccine strategies. The importance of developing such vaccines lies not only in influenza B prevention, but also in the very attractive prospect of eradicating the influenza B virus in the human population.

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Identification of immunodominant CD8 epitope in the stalk domain of influenza B viral hemagglutinin

Cited by 6 publications

References 34 publications

Synthetic vaccine affords full protection to mice against lethal challenge of influenza B virus of both genetic lineages

Synthetic vaccine affords full protection to mice against lethal challenge of influenza B virus of both genetic lineages

Plant-derived virus-like particle vaccines drive cross-presentation of influenza A hemagglutinin peptides by human monocyte-derived macrophages

Influenza B: Prospects for the Development of Cross-Protective Vaccines

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