Peptide Epitope Hot Spots of CD4 T Cell Recognition Within Influenza Hemagglutinin During the Primary Response to Infection

Knowlden, Zackery A. G.; Richards, Katherine A.; Moritzky, Savannah A; Sant, Andrea J.

doi:10.3390/pathogens8040220

Cited by 12 publications

(13 citation statements)

References 86 publications

(145 reference statements)

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“…We speculate that the increased CD4 T cell epitope abundance of the HA-ferritin fusion protein constructs may influence the GC B cell response through provision of additional T cell help for cognate B cells. We, and others, have shown that several limited regions within the H1 HA molecule contained the immunodominant CD4 T cell epitopes in both inbred mice and human donors expressing diverse MHC class II alleles 48,63 . Previous studies in pre-clinical animal models indicated that when the antigen-specificity of the T FH repertoire was assessed by AIM assay with HA head and HA stem-derived peptide pools, the HA head was significantly enriched for antigenspecific T FH relative to the HA stem domain 64 .…”

Section: Discussionmentioning

confidence: 81%

“…To determine the epitope specificity of the CD4 T cell response at the level of single peptides, a peptide library of 15-mer peptides overlapping by 11 residues covering the sequence of H. pylori ferritin (Table 1) was used. To test CD4 T cell reactivity directed against HA, we tested an array of major peptide epitopes from A/New/Caledonia/99 HA that had been previously defined by overlapping peptide matrices spanning the full sequence of HA in mouse strains expressing different MHC class II haplotypes (Table 2) [48][49][50][51][52] .…”

Section: Resultsmentioning

confidence: 99%

“…Transgenic mice expressing HLA-DR1 or HLA-DR4, class II molecules commonly expressed in humans, were immunized with HA-Fe-nanoparticles, and CD4 T cell responses were assayed using cytokine ELISpot assays. Cells were stimulated with overlapping peptides spanning the sequence of H. pylori ferritin or previously defined major peptide epitopes from A/New/Caledonia/99 HA 48 . Even in HLA-DR1 transgenic mice, where we previously discovered an exceptionally high number of CD4 T cell epitopes in HA 51 , strong reactivity to ferritin-derived peptides was observed, where ferritin peptides FE1, FE5, and FE97 elicited readily detectable responses (Fig.…”

Section: Resultsmentioning

confidence: 99%

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CD4 T cell epitope abundance in ferritin core potentiates responses to hemagglutinin nanoparticle vaccines

et al. 2022

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Nanoparticle vaccines based on H. pylori ferritin are increasingly used as a vaccine platform for many pathogens, including RSV, influenza, and SARS-CoV-2. They have been found to elicit enhanced, long-lived B cell responses. The basis for improved efficacy of ferritin nanoparticle vaccines remains unresolved, including whether recruitment of CD4 T cells specific for the ferritin component of these vaccines contributes to cognate help in the B cell response. Using influenza HA-ferritin nanoparticles as a prototype, we have performed an unbiased assessment of the CD4 T cell epitope composition of the ferritin particles relative to that contributed by influenza HA using mouse models that express distinct constellations of MHC class II molecules. The role that these CD4 T cells play in the B cell responses was assessed by quantifying follicular helper cells (TFH), germinal center (GC) B cells, and antibody secreting cells. When mice were immunized with equimolar quantities of soluble HA-trimers and HA-Fe nanoparticles, HA-nanoparticle immunized mice had an increased overall abundance of TFH that were found to be largely ferritin-specific. HA-nanoparticle immunized mice had an increased abundance of HA-specific isotype-switched GC B cells and HA-specific antibody secreting cells (ASCs) relative to mice immunized with soluble HA-trimers. Further, there was a strong, positive correlation between CD4 TFH abundance and GC B cell abundance. Thus, availability of helper CD4 T cell epitopes may be a key additional mechanism that underlies the enhanced immunogenicity of ferritin-based HA-Fe-nanoparticle vaccines.

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Section: Discussionmentioning

confidence: 81%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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CD4 T cell epitope abundance in ferritin core potentiates responses to hemagglutinin nanoparticle vaccines

et al. 2022

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“…A study by Argentinean scientists showed that vaccination with proteins leads to CD4 T-cells and infection recalls their memory. In addition, the hemagglutinin released by infected or dying cells, rather than infectious virions, is the main source of antigen for antigen presentation after the infection (Knowlden, et al 2019).…”

Section: Discussionmentioning

confidence: 99%

Hemagglutination inhibition antibody titers as a correlate of protection against influenza disease in the 2018/2019 epidemic season in Poland

et al. 2020

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The aim of this study was to determine the level of antibodies against hemagglutinin of influenza viruses in the sera of people in the seven age groups in the epidemic season 2018/2019 in Poland. The level of anti-hemagglutinin antibodies was determined by hemagglutination inhibition test (HAI). 1050 clinical samples from all over the country were tested. The level of antibodies against influenza viruses was highest in the 10–14 age group for A/Singapore/INFIMH-16-0019/2016 (H3N2) and B/Phuket/3073/2013 Yamagata lineage antigens. These results confirm the circulation of four antigenically different influenza virus strains, two subtypes of influenza A virus – A/Michigan/45/2015 (H1N1)pdm09 and A/Singapore/INFIMH-16-0019/2016 (H3N2) and two lineages of influenza B virus – B/Colorado/06/2017 – Victoria lineage and B/Phuket/3073/2013 Yamagata lineage.

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“…In this special issue, Zackery et al ask whether HA epitopes recognized by CD 4 T cells in the primary response to infection are equally distributed across the HA protein. Using mice, their studies revealed that the HA-specific CD 4 T cell epitopes cluster in two distinct regions of HA, which could be important in the development of universal vaccines against influenza [6].…”

mentioning

confidence: 99%

Influenza Virus and Vaccination

Nogales¹,

DeDiego

2020

Pathogens

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Influenza virus infections represent a serious public health problem causing contagious respiratory disease and substantial morbidity and mortality in humans, resulting in a considerable economic burden worldwide. Notably, the number of deaths due to influenza exceeds that of any other known pathogen. Moreover, influenza infections can differ in their intensity, from mild respiratory disease to pneumonia, which can lead to death. Articles in this Special Issue have addressed different aspects of influenza in human health, and the advances in influenza research leading to the development of better therapeutics and vaccination strategies, with a special focus on the study of factors associated with innate or adaptive immune responses to influenza vaccination and/or infection.

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Peptide Epitope Hot Spots of CD4 T Cell Recognition Within Influenza Hemagglutinin During the Primary Response to Infection

Cited by 12 publications

References 86 publications

CD4 T cell epitope abundance in ferritin core potentiates responses to hemagglutinin nanoparticle vaccines

CD4 T cell epitope abundance in ferritin core potentiates responses to hemagglutinin nanoparticle vaccines

Hemagglutination inhibition antibody titers as a correlate of protection against influenza disease in the 2018/2019 epidemic season in Poland

Influenza Virus and Vaccination

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