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Principal Investigator: John Mascola
Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Fiscal Year: 2020
Award: $253,477
Funding agency: National Institute of Allergy and Infectious Diseases
During the past year, the Virology Laboratory has collaborated with other intramural NIAID labs and other external collaborators to develop a pseudovirus neutralization assay and an mRNA vaccine expressing the prefusion-stabilized SARS-CoV-2 spike trimer (mRNA-1273). For the neutralization assay, we have provided technical and software assistance to other VRC labs, and developed a shared Standard Operating Procedure. The assay is being used by laboratory staff to evaluate human serum samples from individuals recovering from COVID-19 and from volunteers in the Phase I clinical trial of the Moderna mRNA1273 vaccine. We are also isolating and characterizing monoclonal antibodies from individuals recovering from COVID-19 disease, assessing for SARS-CoV-2 neutralizing antibodies, which are valuable research reagents with great potential for therapeutic and prevention purposes.
For the mRNA vaccine, we show that mRNA-1273 induces both potent neutralizing antibody responses to wild-type (D614) and D614G mutant2 SARS-CoV-2, as well as high T cells responses. Importantly, this mRNA vaccine protects against SARS-CoV-2 infection in the lungs and noses of mice and nonhuman primate without evidence of immunopathology. Vaccinated nonhuman primates with mRNA-1273 induced robust immune responses with rapid protection in the upper and lower airways, and no pathologic changes in the lung. Vaccine recipients participating in the clinical trial have shown a robust neutralizing response to SARS-CoV-2.
Terms: <2019 novel coronavirus><2019-nCoV><Animals><Antibodies><Antibody Response><Assay><Bioassay><Biologic Assays><Biological Assay><Blood Serum><COVID-19><COVID19><Clinical><Clinical Treatment Moab><Clinical Trials><Computer software><Development><Disease><Disorder><ELISA><Early-Stage Clinical Trials><Enzyme-Linked Immunosorbent Assay><Human><Immune response><Immunize><Immunological response><Individual><Infection><Laboratories><Lung><Lung Respiratory System><Messenger RNA><Mice><Mice Mammals><Modern Man><Monoclonal Antibodies><Murine><Mus><NIAID><Nasal><Nasal Passages Nose><National Institute of Allergy and Infectious Disease><Nose><Pathologic><Phase 1 Clinical Trials><Phase I Clinical Trials><Prevention><Procedures><RNA vaccine><Reagent><Research><Respiratory System, Nose, Nasal Passages><SARS-CoV-2><SARS-CoV2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related coronavirus 2><Sampling><Serum><Severe acute respiratory syndrome coronavirus 2><Software><Standardization><T cell response><Therapeutic><Vaccinated><Vaccines><Virus><Wuhan coronavirus><corona virus disease 2019><coronavirus disease 2019><developmental><host response><immunopathology><immunoresponse><mAbs><mRNA><mRNA vaccine><neutralizing antibody><non-human primate><nonhuman primate><phase I protocol><pre-clinical><preclinical><pulmonary><response><vaccine candidate><virology><volunteer>