Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA717250 | ENA |
REPOSITORIES: ENA
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Project description:Despite the success of currently authorized vaccines for the reduction of severe COVID-19 disease risk, rapidly emerging viral variants continue to drive pandemic waves of infection, resulting in numerous global public health challenges. Progress will depend on future advances in prophylactic vaccine activity, including advancement of candidates capable of generating more potent induction of cross-reactive T cells and durable cross-reactive antibody responses. Here we evaluated an Amphiphile (AMP) adjuvant, AMP-CpG, admixed with SARS-CoV-2 Spike receptor binding domain (RBD) immunogen, as a lymph node-targeted protein subunit vaccine (ELI-005) in mice and non-human primates (NHPs). AMP-mediated targeting of CpG DNA to draining lymph nodes resulted in comprehensive local immune activation characterized by extensive transcriptional reprogramming, inflammatory proteomic milieu, and activation of innate immune cells as key orchestrators of antigen-directed adaptive immunity. Prime-boost immunization with AMP-CpG in mice induced potent and durable T cell responses in multiple anatomical sites critical for prophylactic efficacy and prevention of severe disease. Long-lived memory responses were rapidly expanded upon re-exposure to antigen. In parallel, RBD-specific antibodies were long-lived, and exhibited cross-reactive recognition of variant RBD. AMP-CpG-adjuvanted prime-boost immunization in NHPs was safe and well tolerated, while promoting multi-cytokine-producing circulating T cell responses cross-reactive across variants of concern (VOC). Expansion of RBD-specific germinal center (GC) B cells in lymph nodes correlated to rapid seroconversion with variant-specific neutralizing antibody responses exceeding those measured in convalescent human plasma. These results demonstrate the promise of lymph-node adjuvant-targeting to coordinate innate immunity and generate robust adaptive responses critical for vaccine efficacy.
2022-11-02 | GSE214564 | GEO
Project description:Despite the success of currently authorized vaccines for the reduction of severe COVID-19 disease risk, rapidly emerging viral variants continue to drive pandemic waves of infection, resulting in numerous global public health challenges. Progress will depend on future advances in prophylactic vaccine activity, including advancement of candidates capable of generating more potent induction of cross-reactive T cells and durable cross-reactive antibody responses. Here we evaluated an Amphiphile (AMP) adjuvant, AMP-CpG, admixed with SARS-CoV-2 Spike receptor binding domain (RBD) immunogen, as a lymph node-targeted protein subunit vaccine (ELI-005) in mice and non-human primates (NHPs). AMP-mediated targeting of CpG DNA to draining lymph nodes resulted in comprehensive local immune activation characterized by extensive transcriptional reprogramming, inflammatory proteomic milieu, and activation of innate immune cells as key orchestrators of antigen-directed adaptive immunity. Prime-boost immunization with AMP-CpG in mice induced potent and durable T cell responses in multiple anatomical sites critical for prophylactic efficacy and prevention of severe disease. Long-lived memory responses were rapidly expanded upon re-exposure to antigen. In parallel, RBD-specific antibodies were long-lived, and exhibited cross-reactive recognition of variant RBD. AMP-CpG-adjuvanted prime-boost immunization in NHPs was safe and well tolerated, while promoting multi-cytokine-producing circulating T cell responses cross-reactive across variants of concern (VOC). Expansion of RBD-specific germinal center (GC) B cells in lymph nodes correlated to rapid seroconversion with variant-specific neutralizing antibody responses exceeding those measured in convalescent human plasma. These results demonstrate the promise of lymph-node adjuvant-targeting to coordinate innate immunity and generate robust adaptive responses critical for vaccine efficacy.
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Project description:The rapid global spread of SARS-CoV-2 and resultant mortality and social disruption have highlighted the need to better understand coronaviral immunity to expedite vaccine development efforts. Multiple candidate vaccines with the goal of eliciting protective neutralising antibodies targeting the viral spike glycoprotein are rapidly advancing to clinical trial. However, the immunogenic properties of the spike in human populations are unresolved. To address this, we undertook an in-depth characterisation of humoral and cellular immunity against SARS-CoV-2 spike in humans following mild to moderate SARS-CoV-2 infection. We find serological antibody responses against spike are routinely elicited by infection and correlate with plasma neutralising and ACE2 inhibitory activity. Expanded populations of spike-specific memory B cells and circulating T follicular helper cells (cTFH) were detected within convalescent donors, while responses to receptor binding domain constitute a minor fraction. Using regression analysis, we find high serum neutralisation activity was associated with increased spike-specific antibody, but notably also with the relative distribution of some spike-specific cTFH subsets. Thus both qualitative and quantitative features of B and T cell immunity to spike constitute informative biomarkers to assess protective potential of novel SARS-CoV-2 vaccines
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Project description:Saliva based diagnostics is a rapidly evolving field due to the large potential of saliva and the simple sample collection. A systematic comparison of IgG antibody profiles in saliva and plasma is currently lacking in scientific literature. Our hypothesis is that IgG profiles are equal in blood and saliva. By showing the equality of the profiles and relative IgG antigenic reactivities towards proteins and peptides we provide evidence that plasma IgG reactivities can be inferred from saliva IgG reactivities. IgG antibodies were isolated from human saliva and plasma samples. The reactivities of IgG isolates were analysed on peptide microarrays displaying linear epitopes of EBV (EBNA1 protein) and HBV (Large envelope protein) virus. Peptide arrays were printed by JPT Peptide Technologies (Berlin, Germany). We show high similarity of saliva and plasma IgG profiles on these two platforms and argue for generalisation from this subset to the whole immunological IgG antibody profile.
2018-07-17 | GSE117141 | GEO
Project description:Saliva based diagnostics is a rapidly evolving field due to the large potential of saliva and the simple sample collection. A systematic comparison of IgG antibody profiles in saliva and plasma is currently lacking in scientific literature. Our hypothesis is that IgG profiles are equal in blood and saliva. By showing the equality of the profiles and relative IgG antigenic reactivities towards proteins and peptides we provide evidence that plasma IgG reactivities can be inferred from saliva IgG reactivities. IgG antibodies were isolated from human saliva and plasma samples. The reactivities of IgG isolates were analysed on peptide microarrays displaying linear epitopes of EBV (EBNA1 protein) and HBV (Large envelope protein) virus. Peptide arrays were printed by JPT Peptide Technologies (Berlin, Germany). We show high similarity of saliva and plasma IgG profiles on these two platforms and argue for generalisation from this subset to the whole immunological IgG antibody profile.
2018-07-17 | GSE117140 | GEO
Project description:The on-going COVID-19 pandemic requires a deeper understanding of the long-term antibody responses that persist following SARS-CoV-2 infection. To that end, we determined epitope-specific IgG antibody responses in COVID-19 convalescent sera collected at 5 months post-diagnosis and compared that to sera from naïve individuals. Each serum sample was reacted with a high-density peptide microarray representing the complete proteome of SARS-CoV-2 as 15 mer peptides with 11 amino acid overlap and homologs of spike glycoprotein, nucleoprotein, membrane protein, and envelope small membrane protein from related human coronaviruses. Binding signatures were compared between COVID-19 convalescent patients and naïve individuals using the web service tool EPIphany.
2022-02-05 | E-MTAB-10740 | biostudies-arrayexpress
Project description:Long-term immunity to SARS-CoV-2 infection, comprising neutralizing antibodies and T cell-mediated immunity, in a very large majority of the population, is required to reduce the current pandemic. We have investigated in detail the association between memory CD4 and CD8 T cells in recovered COVID-19 subjects, and their levels of neutralizing antibodies.The results show that RBD-specific memory CD4 T cells were particularly variable, and up to half of recovered individuals lacked these CD4 T cells and had much lower neutralizing antibody titres. Conversely, study of additional subjects identified as having low neutralizing antibody titres had very low levels of RBD-specific CD4 T cells. Furthermore, at both the protein and transcriptomic levels, these low antibody subjects had spike-specific CD4 T cells with a higher proportion of an inhibitory phenotype, including Foxp3 and CTLA-4, and less effector phenotype with T-bet and cytotoxic granzymes and perforin. Vaccination led to an improvement in RBD-specific memory CD4 T cells and neutralizing antibody titres in these at-risk subjects. Our results suggest that epitopes within the RBD-region should be the particular target of booster vaccines.
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