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Principal Investigator: Lesia Dropulic
Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Fiscal Year: 2022
Award: $680,544
Funding agency: National Institute of Allergy and Infectious Diseases
This project includes the evaluation of a vaccine candidate targeting SARS-CoV-2, mRNA-1273, that was administered to healthy volunteers in a phase 1 trial (DMID 20-0003). This project also includes the collection of samples for translational immunology research from participants who have been vaccinated with a COVID-19 vaccine or were actively infected or had recovered from SARS-CoV-2 infection. Sample collection was conducted under the VRC 200 protocol. This project and collection of samples support the broader VRC mission of developing vaccines for pandemic preparedness and evaluating immune responses to these vaccines.
VRC 200: A Multicenter Specimen Collection Protocol to Obtain Human Biological Samples for Research Studies
Several studies have been published in FY22 using samples collected under this protocol:
1)SARS-CoV-2 Omicron Variant Neutralization after mRNA-1273 Booster Vaccination. N Engl J Med. 2022 Mar 17;386(11):1088-1091. doi: 10.1056/NEJMc2119912. Epub 2022 Jan 26. PMID: 35081298; PMCID: PMC8809504.
In this study, Pajon R. et al. investigated neutralizing antibody responses against the SARS-CoV-2 omicron variant after mRNA-1273 booster vaccination. They found that one month after the two dose primary vaccination series, neutralization titers were 35 times lower against the omicron variant compared to the prototypical D614G SARS-CoV-2 variant. However, after a booster dose of mRNA 1273, the neutralization titers against the omicron variant were 20 times higher than those assessed after the second dose of vaccine. The decline in neutralization titers against the omicron variant 6 months after the booster injection were similar to the decline in neutralization titers against the D614G variant 7 months after the second dose.
2) Convergent epitopes specificities, V gene usage and public clones elicited by primary exposure to SARS-CoV-2. bioRxiv. 2022 Mar 29:2022.03.28.486152. doi: 10.1101/2022.03.28.486152. Preprint. PMID: 35378757.
Lima N et al. using a high throughput approach to obtain immunoglobulin sequences and produce monoclonal antibodies for functional assessment of single B cells found that infection with any SARS-CoV-2 variant elicited similar cross-binding antibody responses exhibiting a remarkably conserved hierarchy of epitope immunodominance. In addition, convergent V gene usage and similar public B cell clones were elicited regardless of the variant, suggesting that despite antigenic variation these consistent immunological findings may account for the continued efficacy of vaccines based on a single ancestral variant.
3) Structural basis for potent antibody neutralization of SARS-CoV-2 variants including B.1.1.529. Science. 2022 Apr 22;376(6591):eabn8897. doi: 10.1126/science.abn8897. Epub 2022 Apr 22. PMID: 35324257.
Zhou T. et al identified antibodies that maintain the ability to neutralize the omicron variant and used functional and structural studies to determine how they recognize the omicron spike protein.
4) A multispecific antibody confers pan-reactive SARS-CoV-2 neutralization and prevents immune escape. bioRxiv. 2022 Aug 4:2022.07.29.502029. doi: 10.1101/2022.07.29.502029. Preprint. PMID: 35982683.
Misasi J et al. describe the development of a trivalent SARS-CoV-2 multi-specific antibody that potently neutralized all major SARS-C0V-2 variants.
DMID 20-0003: CTP was a site for the DMID 20-0003 clinical trial: A Phase I, Open-Label, Dose-Ranging Study of the Safety and Immunogenicity of 2019-nCoV Vaccine (mRNA-1273) in Healthy Adults (NCT04283461). A total of 20 participants aged 56-70 (n=10) and 71 (n=10) were enrolled starting on June 2, 2020. All participants received 2 doses of 50mcg mRNA-1273. 12 subjects participated in an optional boost sub-study starting in March 2021 and received an additional 50mcg dose of mRNA-1273. The last study visit was in April 2022 and all subjects are now off study.
Several publications have arisen from this trial:
1) Jackson LA et al. mRNA-1273 Study Group. An mRNA Vaccine against SARS-CoV-2 - Preliminary Report. N Engl J Med. 2020 Nov 12;383(20):1920-1931. doi: 10.1056/NEJMoa2022483. Epub 2020 Jul 14.
2) Anderson EJ et al. mRNA-1273 Study Group. Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults. N Engl J Med. 2020 Dec 17;383(25):2427-2438. doi: 10.1056/NEJMoa2028436. Epub 2020 Sep 29.
3)Widge AT et al. mRNA-1273 Study Group. Durability of Responses after SARS-CoV-2 mRNA-1273 Vaccination. N Engl J Med. 2021 Jan 7;384(1):80-82. doi: 10.1056/NEJMc2032195. Epub 2020 Dec 3. PMID: 33270381; PMCID: PMC7727324.
4)Doria-Rose N et al.mRNA-1273 Study Group. Antibody Persistence through 6 Months after the Second Dose of mRNA-1273 Vaccine for Covid-19. N Engl J Med. 2021 Jun 10;384(23):2259-2261. doi: 10.1056/NEJMc2103916. Epub 2021 Apr 6. Erratum in: N Engl J Med. 2022 Feb 3;386(5):500. PMID: 33822494; PMCID: PMC8524784.
5)Anderson E et al. Safety and Immunogenicity of a Third Dose of SARS-CoV-2 mRNA Vaccine: An Interim Analysis Sq. 2022 May 3;rs.3.rs-1222037. doi: 10.21203/rs.3.rs-1222037/v1. Preprint
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