Nucleic Acid-Based Vaccine

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Hsin-wei Chen - One of the best experts on this subject based on the ideXlab platform.

  • DNA vaccination induced protective immunity against SARS CoV-2 infection in hamsterss.
    'Public Library of Science (PLoS)', 2021
    Co-Authors: Kit Man Chai, Tsai-teng Tzeng, Kuan-yin Shen, Hung-chun Liao, Jhe-jhih Lin, Mei-yu Chen, Horng-yunn Dou, Ching-len Liao, Hsin-wei Chen
    Abstract:

    The development of efficient Vaccines against COVID-19 is an emergent need for global public health. The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major target for the COVID-19 Vaccine. To quickly respond to the outbreak of the SARS-CoV-2 pandemic, a Nucleic Acid-Based Vaccine is a novel option, beyond the traditional inactivated virus Vaccine or recombinant protein Vaccine. Here, we report a DNA Vaccine containing the spike gene for delivery via electroporation. The spike genes of SARS-CoV and SARS-CoV-2 were codon optimized for mammalian cell expression and then cloned into mammalian cell expression vectors, called pSARS-S and pSARS2-S, respectively. Spike protein expression was confirmed by immunoblotting after transient expression in HEK293T cells. After immunization, sera were collected for antigen-specific antibody and neutralizing antibody titer analyses. We found that both pSARS-S and pSARS2-S immunization induced similar levels of antibodies against S2 of SARS-CoV-2. In contrast, only pSARS2-S immunization induced antibodies against the receptor-binding domain of SARS-CoV-2. We further found that pSARS2-S immunization, but not pSARS-S immunization, could induce very high titers of neutralizing antibodies against SARS-CoV-2. We further analyzed SARS-CoV-2 S protein-specific T cell responses and found that the immune responses were biased toward Th1. Importantly, pSARS2-S immunization in hamsters could induce protective immunity against SARS-CoV-2 challenge in vivo. These data suggest that DNA vaccination could be a promising approach for protecting against COVID-19

Kit Man Chai - One of the best experts on this subject based on the ideXlab platform.

  • DNA vaccination induced protective immunity against SARS CoV-2 infection in hamsterss.
    'Public Library of Science (PLoS)', 2021
    Co-Authors: Kit Man Chai, Tsai-teng Tzeng, Kuan-yin Shen, Hung-chun Liao, Jhe-jhih Lin, Mei-yu Chen, Horng-yunn Dou, Ching-len Liao, Hsin-wei Chen
    Abstract:

    The development of efficient Vaccines against COVID-19 is an emergent need for global public health. The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major target for the COVID-19 Vaccine. To quickly respond to the outbreak of the SARS-CoV-2 pandemic, a Nucleic Acid-Based Vaccine is a novel option, beyond the traditional inactivated virus Vaccine or recombinant protein Vaccine. Here, we report a DNA Vaccine containing the spike gene for delivery via electroporation. The spike genes of SARS-CoV and SARS-CoV-2 were codon optimized for mammalian cell expression and then cloned into mammalian cell expression vectors, called pSARS-S and pSARS2-S, respectively. Spike protein expression was confirmed by immunoblotting after transient expression in HEK293T cells. After immunization, sera were collected for antigen-specific antibody and neutralizing antibody titer analyses. We found that both pSARS-S and pSARS2-S immunization induced similar levels of antibodies against S2 of SARS-CoV-2. In contrast, only pSARS2-S immunization induced antibodies against the receptor-binding domain of SARS-CoV-2. We further found that pSARS2-S immunization, but not pSARS-S immunization, could induce very high titers of neutralizing antibodies against SARS-CoV-2. We further analyzed SARS-CoV-2 S protein-specific T cell responses and found that the immune responses were biased toward Th1. Importantly, pSARS2-S immunization in hamsters could induce protective immunity against SARS-CoV-2 challenge in vivo. These data suggest that DNA vaccination could be a promising approach for protecting against COVID-19

David K Gifford - One of the best experts on this subject based on the ideXlab platform.

  • robust computational design and evaluation of peptide Vaccines for cellular immunity with application to sars cov 2
    bioRxiv, 2020
    Co-Authors: Ge Liu, Brandon Carter, Trenton Bricken, Siddhartha Jain, Mathias Viard, Mary Carrington, David K Gifford
    Abstract:

    We present a combinatorial machine learning method to evaluate and optimize peptide Vaccine formulations, and we find for SARS-CoV-2 that it provides superior predicted display of viral epitopes by MHC class I and MHC class II molecules over populations when compared to other candidate Vaccines. Our method is robust to idiosyncratic errors in the prediction of MHC peptide display and considers target population HLA haplotype frequencies during optimization. To minimize clinical development time our methods validate Vaccines with multiple peptide presentation algorithms to increase the probability that a Vaccine will be effective. We optimize an objective function that is based on the presentation likelihood of a diverse set of Vaccine peptides conditioned on a target population HLA haplotype distribution and expected epitope drift. We produce separate peptide formulations for MHC class I loci (HLA-A, HLA-B, and HLA-C) and class II loci (HLA-DP, HLA-DQ, and HLA-DR) to permit signal sequence based cell compartment targeting using Nucleic acid based Vaccine platforms. Our SARS-CoV-2 MHC class I Vaccine formulations provide 93.21% predicted population coverage with at least five Vaccine peptide-HLA hits on average in an individual (≥ 1 peptide 99.91%) with all Vaccine peptides perfectly conserved across 4,690 geographically sampled SARS-CoV-2 genomes. Our MHC class II Vaccine formulations provide 90.17% predicted coverage with at least five Vaccine peptide-HLA hits on average in an individual with all peptides having observed mutation probability ≤ 0.001. We evaluate 29 previously published peptide Vaccine designs with our evaluation tool with the requirement of having at least five Vaccine peptide-HLA hits per individual, and they have a predicted maximum of 58.51% MHC class I coverage and 71.65% MHC class II coverage given haplotype based analysis. We provide an open source implementation of our design methods (OptiVax), Vaccine evaluation tool (EvalVax), as well as the data used in our design efforts.

Ching-len Liao - One of the best experts on this subject based on the ideXlab platform.

  • DNA vaccination induced protective immunity against SARS CoV-2 infection in hamsterss.
    'Public Library of Science (PLoS)', 2021
    Co-Authors: Kit Man Chai, Tsai-teng Tzeng, Kuan-yin Shen, Hung-chun Liao, Jhe-jhih Lin, Mei-yu Chen, Horng-yunn Dou, Ching-len Liao, Hsin-wei Chen
    Abstract:

    The development of efficient Vaccines against COVID-19 is an emergent need for global public health. The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major target for the COVID-19 Vaccine. To quickly respond to the outbreak of the SARS-CoV-2 pandemic, a Nucleic Acid-Based Vaccine is a novel option, beyond the traditional inactivated virus Vaccine or recombinant protein Vaccine. Here, we report a DNA Vaccine containing the spike gene for delivery via electroporation. The spike genes of SARS-CoV and SARS-CoV-2 were codon optimized for mammalian cell expression and then cloned into mammalian cell expression vectors, called pSARS-S and pSARS2-S, respectively. Spike protein expression was confirmed by immunoblotting after transient expression in HEK293T cells. After immunization, sera were collected for antigen-specific antibody and neutralizing antibody titer analyses. We found that both pSARS-S and pSARS2-S immunization induced similar levels of antibodies against S2 of SARS-CoV-2. In contrast, only pSARS2-S immunization induced antibodies against the receptor-binding domain of SARS-CoV-2. We further found that pSARS2-S immunization, but not pSARS-S immunization, could induce very high titers of neutralizing antibodies against SARS-CoV-2. We further analyzed SARS-CoV-2 S protein-specific T cell responses and found that the immune responses were biased toward Th1. Importantly, pSARS2-S immunization in hamsters could induce protective immunity against SARS-CoV-2 challenge in vivo. These data suggest that DNA vaccination could be a promising approach for protecting against COVID-19

Horng-yunn Dou - One of the best experts on this subject based on the ideXlab platform.

  • DNA vaccination induced protective immunity against SARS CoV-2 infection in hamsterss.
    'Public Library of Science (PLoS)', 2021
    Co-Authors: Kit Man Chai, Tsai-teng Tzeng, Kuan-yin Shen, Hung-chun Liao, Jhe-jhih Lin, Mei-yu Chen, Horng-yunn Dou, Ching-len Liao, Hsin-wei Chen
    Abstract:

    The development of efficient Vaccines against COVID-19 is an emergent need for global public health. The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major target for the COVID-19 Vaccine. To quickly respond to the outbreak of the SARS-CoV-2 pandemic, a Nucleic Acid-Based Vaccine is a novel option, beyond the traditional inactivated virus Vaccine or recombinant protein Vaccine. Here, we report a DNA Vaccine containing the spike gene for delivery via electroporation. The spike genes of SARS-CoV and SARS-CoV-2 were codon optimized for mammalian cell expression and then cloned into mammalian cell expression vectors, called pSARS-S and pSARS2-S, respectively. Spike protein expression was confirmed by immunoblotting after transient expression in HEK293T cells. After immunization, sera were collected for antigen-specific antibody and neutralizing antibody titer analyses. We found that both pSARS-S and pSARS2-S immunization induced similar levels of antibodies against S2 of SARS-CoV-2. In contrast, only pSARS2-S immunization induced antibodies against the receptor-binding domain of SARS-CoV-2. We further found that pSARS2-S immunization, but not pSARS-S immunization, could induce very high titers of neutralizing antibodies against SARS-CoV-2. We further analyzed SARS-CoV-2 S protein-specific T cell responses and found that the immune responses were biased toward Th1. Importantly, pSARS2-S immunization in hamsters could induce protective immunity against SARS-CoV-2 challenge in vivo. These data suggest that DNA vaccination could be a promising approach for protecting against COVID-19