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| covid-19_vaccines:research_and_development [2022/08/13 17:00] pamela [NIH Funding SARS - Coronavirus Vaccine Development] | covid-19_vaccines:research_and_development [2022/08/13 17:13] (current) pamela [NIH Funding SARS - Coronavirus Vaccine Development] | ||
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| ==== NIH Funding SARS - Coronavirus Vaccine Development ==== | ==== NIH Funding SARS - Coronavirus Vaccine Development ==== | ||
| - | 2004 Human Antibodies and Targeted Vaccines Against SARS-CoV | + | 2002 |
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| + | Coronavirus vaccine development | ||
| + | Project Number1ZIAAI005125-02 | ||
| + | Contact PI/Project LeaderGRAHAM, | ||
| + | Awardee OrganizationNATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES | ||
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| + | When the MERS CoV outbreak raised global health concerns, we initiated a program to develop a candidate vaccine. Starting from [[:Spike glycoprotein]] (S) sequences, we developed an immunization strategy consisting of a full-length S DNA prime and a S1 subunit protein boost that elicited high titers of neutralizing antibodies against eight different MERS-CoV strains. Immune sera contained potent neutralizing antibodies targeting the receptor binding domain (RBD), non-RBD portions of S1, and the S2 subunit. | ||
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| + | From the immunized mice we produced a panel of hybridomas and produced [[: | ||
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| + | 2004 | ||
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| + | Human Antibodies and Targeted Vaccines Against SARS-CoV | ||
| Project Number5U01AI061318-05 | Project Number5U01AI061318-05 | ||
| Contact PI/Project Leader MARASCO, WAYNE A. | Contact PI/Project Leader MARASCO, WAYNE A. | ||
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| If these studies are successful, we will move into a non-human primate model of SARS to determine if this human Mab can ultimately be used in the emergency prophylaxis and treatment of SARS in humans. We will also study the mechanisms of neutralization escape that may develop after treatment of SARS-CoV with 80R Mab. For these studies, we will generate S1 neutralization escape mutants in vitro and then characterize the S1 mutants for the amino acid changes in the [[:S1 protein]], the changes in binding affinity of the mutant S1 proteins for the ACE2 receptor and for 80R Mab, the ability of the S1 mutant viruses to enter cells at lower [[:ACE2 receptor]] concentrations and the ability of the S1 mutant viruses induce cytopathic and pathogenic effects in vitro and in vivo. We will also identify neutralizing human monoclonal antibodies to epitopes other than the 80R epitope on S1 protein and to isolate high-affinity neutralizing human antibodies against S2 and membrane (M) protein. | If these studies are successful, we will move into a non-human primate model of SARS to determine if this human Mab can ultimately be used in the emergency prophylaxis and treatment of SARS in humans. We will also study the mechanisms of neutralization escape that may develop after treatment of SARS-CoV with 80R Mab. For these studies, we will generate S1 neutralization escape mutants in vitro and then characterize the S1 mutants for the amino acid changes in the [[:S1 protein]], the changes in binding affinity of the mutant S1 proteins for the ACE2 receptor and for 80R Mab, the ability of the S1 mutant viruses to enter cells at lower [[:ACE2 receptor]] concentrations and the ability of the S1 mutant viruses induce cytopathic and pathogenic effects in vitro and in vivo. We will also identify neutralizing human monoclonal antibodies to epitopes other than the 80R epitope on S1 protein and to isolate high-affinity neutralizing human antibodies against S2 and membrane (M) protein. | ||
| - | We will identify antigenic protein fragments (APFs) from the [[SARS-CoV Spike]] (S) and M proteins by screening with natural peptide libraries derived from SARS-CoV. For these studies, we will use the naturally occurring neutralizing antibodies in convalescent SARS serum as well as the 80R Mab and the additional neutralizing antibodies to identify the neutralizing epitopes. Finally, these APFs will be incorporated into the design of optimal forms of S-IgG and M-IgG fusion proteins that can be used as immunogens for induction of humoral immune responses against SARS viral proteins, which, in turn, may block infection by the SARS virus. We will also examine the " | + | We will identify antigenic protein fragments (APFs) from the [[SARS-CoV Spike]] (S) and M proteins by screening with natural peptide libraries derived from SARS-CoV. For these studies, we will use the naturally occurring neutralizing antibodies in convalescent SARS serum as well as the 80R Mab and the additional neutralizing antibodies to identify the neutralizing epitopes. Finally, these APFs will be incorporated into the design of optimal forms of S-IgG and M-IgG fusion proteins that can be used as immunogens for induction of humoral immune responses against SARS viral proteins, which, in turn, may block infection by the SARS virus. We will also examine the " |
| === Funded SARS Monoclonal Study === ((https:// | === Funded SARS Monoclonal Study === ((https:// | ||