Ontology highlight
ABSTRACT:
PROVIDER: PRJNA729513 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14514445_1.fastq.gz | Fastqsanger.gz | |||
| SRR14514445_2.fastq.gz | Fastqsanger.gz | |||
| SRR14514446_1.fastq.gz | Fastqsanger.gz | |||
| SRR14514446_2.fastq.gz | Fastqsanger.gz | |||
| SRR14514447_1.fastq.gz | Fastqsanger.gz |
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Project description:Prevalent, protective, and convergent IgG recognition of SARS-CoV-2 non-RBD spike epitopes in COVID-19 convalescent plasma
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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.
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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.
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