Effect of AMP-CpG on lymph node immune response in rhesus macaque
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PROVIDER: PRJNA885864 | ENA |
REPOSITORIES: ENA
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Project description:Effect of AMP-CpG on lymph node immune response in mouse and rhesus macaque
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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:Effect of AMP-dT on lymph node immune response in rhesus macaque
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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:Adjuvants are immuno-activators capable of shaping the magnitude and quality of antigen-specific immune responses induced by subunit immunization. Presently, there is an acute need for effective adjuvants that safely induce durable and balanced humoral and cellular responses. Here, we engineered a class of Amphiphile (AMP)-modified, immunostimulatory DNA-adjuvants designed for targeted delivery to lymph nodes and enhanced stimulation of TANK-binding kinase 1 (TBK1)-mediated danger-sensing pathways to generate strong adaptive immunity and long-term memory with potent recall potential. AMP-DNA adjuvants induced robust interferon type-I (IFN-I)-driven inflammatory environments in mouse and non-human primate (NHP) lymph nodes, leading to significantly enhanced cytokine secretion by polyfunctional CD8+ and CD4+ T cells in multiple tissues, as well as strongly elevated TH1-associated and neutralizing antibody responses, in the absence of systemic toxicity. These results demonstrate that AMP-modification enables lymph node-targeted DNA-adjuvants to potently activate IFN-I-signaling to generate substantial cellular and humoral responses crucial for vaccine efficacy.
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Project description:Effect of AMP-CpG on lymph node immune response in mouse
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Project description:Sixteen individual rhesus macaque genomes were compared to a reference macaque genome (R354) on custom-designed sure-print 1M oligonucleotide microarray Agilent (Agilent Technologies) aCGH slide per manufacturer’s recommendations. a custom designed Agilent array-based comparative genomic hybridization (aCGH) platform, which comprises 950,843 unique 60-mer oligonucleotide probes specific to the rhesus macaque reference genome (rheMac2), to compare the genomic DNAs of 17 unrelated rhesus macaques of Indian origin to the genome of an unrelated sample from the same species.
2011-05-11 | E-GEOD-19881 | biostudies-arrayexpress
Project description:The primary goal of this study was to compare the performances of Rhesus Macaque Genome Array and Human Genome U133 Plus 2.0 Array with respect to the detection of differential expressions when rhesus macaque RNA extracts were labeled and hybridized. The secondary goal of this study was to investigate the effect of mismatch position on signal strength in Affymetrix GeneChips by examining naturally occurring mismatches between rhesus macaque transcripts and human probes from Human Genome U133 Plus 2.0 Array. The primary goal of this study was to compare the performances of Rhesus Macaque Genome Array and Human Genome U133 Plus 2.0 Array with respect to the detection of differential expressions when rhesus macaque RNA extracts were labeled and hybridized. The secondary goal of this study was to investigate the effect of mismatch position on signal strength in Affymetrix GeneChips by examining naturally occurring mismatches between rhesus macaque transcripts and human probes from Human Genome U133 Plus 2.0 Array. Keywords: cross hybridization
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