Document text
Principal Investigator: paolo lusso
Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Fiscal Year: 2022
Award: $160,169
Funding agency: National Institute of Allergy and Infectious Diseases
Following the success of our HIV vaccine platform based on co-formulated Env+Gag mRNA in order to produce non-infectious VLPs (Zhang et al., Nat. Med. 27:2234, 2021), in collaboration with Moderna, Inc., we have designed a similar vaccine platform for SARS-CoV-2. The major results obtained include the following:
1. We synthesized different tail-modified SARS-CoV2 envelope spikes (S) in order to facilitate protein-protein interaction and VLP formation with lentivirus core proteins. In order to facilitate the assembly of VLPs containing lentivirus (HIV-1 or SIV) core proteins, we have designed S proteins modified in their cytoplasmic tails (CT) by replacement of the natural tail with either the HIV-1 or SIV gp41 CT. A truncated form of the lentivirus tails has been used, based on our original design for the HIV-1 vaccine, to promote a more efficient surface membrane expression. Moderna Inc. has produced the specific mRNAs according to our design.
2. In vitro, we tested the efficiency of production of VLPs with the modified spike proteins. The spike protein mRNAs were co-transfected into mammalian cells in all possible combinations with mRNAs encoding HIV-1 or SIV Gag or Gag-Pol. The extracellular VLPs were harvested and concentrated by ultracentrifugation on sucrose cushions. The produced VLPs have been extensively characterized both quantitatively and qualitatively using a wide array of physical and immunological assays, including virion capture by mAbs followed by ELISA for lentivirus core antigen quantification, Western blot and others.
3. We have started to test the immunogenicity of our hybrid SARS-CoV-2-SIV VLP-forming vaccine in mice. Preliminary results demonstrate that our VLP-forming vaccine is superior to the SARS-CoV-2 spike protein alone in eliciting neutralizing antibodies.
Thus, our results indicate that VLPs comprising the CoV2 Spike protein and a lentiretrovirus core can be efficiently produced and display the native-like form of the S-protein on their surface. A VLP-forming SARS-CoV-2 vaccine may be more effective than our current vaccines for induction of protective immunity.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV S protein><2019-nCoV spike glycoprotein><2019-nCoV spike protein><2019-nCoV vaccine><Antigens><COVID-19 S protein><COVID-19 spike glycoprotein><COVID-19 spike protein><COVID-19 vaccine><COVID-19 virus><COVID19 S protein><COVID19 spike glycoprotein><COVID19 spike protein><COVID19 vaccine><COVID19 virus><Clinical Research><Clinical Study><Clinical Treatment Moab><CoV emergence><CoV-2><CoV2><Collaborations><Core Protein><Cytoplasmic Domain><Cytoplasmic Tail><Development><ELISA><Enzyme-Linked Immunosorbent Assay><Glycoproteins><HIV vaccine><HIV-1><HIV-1 vaccine><HIV-I><HIV/AIDS Vaccines><HIV1><HIV1 vaccine><Harvest><Human Immunodeficiency Virus Type 1><Human immunodeficiency virus 1><Hybrids><Immune response><Immunity><Immunoblotting><Immunological response><Immunology procedure><Individual><Lentivirinae><Lentivirus><Mammalian Cell><Membrane><Messenger RNA><Mice><Mice Mammals><Monoclonal Antibodies><Murine><Mus><Phase><Production><Proteins><RNA vaccine><RNA-based vaccine><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 S protein><SARS-CoV-2 spike glycoprotein><SARS-CoV-2 spike protein><SARS-CoV-2 vaccine><SARS-CoV2><SARS-CoV2 S protein><SARS-CoV2 spike glycoprotein><SARS-CoV2 spike protein><SARS-CoV2 vaccine><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-coronavirus-2 vaccine><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><SIV><SIV envelope protein gp41><SIV gp40><SIV gp41><Saccharose><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome CoV 2 vaccine><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 S protein><Severe acute respiratory syndrome coronavirus 2 spike glycoprotein><Severe acute respiratory syndrome coronavirus 2 spike protein><Severe acute respiratory syndrome coronavirus 2 vaccine><Severe acute respiratory syndrome related corona virus 2><Simian Immunodeficiency Viruses><Sucrose><Surface><Tail><Testing><Ultracentrifugation><Vaccination><Vaccines><Virion><Virus><Virus Assembly><Virus Particle><Virus-Lenti><Virus-like particle><Western Blotting><Western Immunoblotting><Wuhan coronavirus><base><corona virus disease 2019 vaccine><corona virus emergence><coronavirus disease 2019 S protein><coronavirus disease 2019 spike glycoprotein><coronavirus disease 2019 spike protein><coronavirus disease 2019 vaccine><coronavirus disease 2019 virus><coronavirus disease-19 vaccine><coronavirus disease-19 virus><coronavirus emergence><design><design validation><design verification><designing><developmental><emergent CoV><emergent corona virus><emergent coronavirus><emerging CoV><emerging corona virus><emerging coronavirus><enzyme linked immunoassay><experience><extracellular><hCoV19><host response><human immunodeficiency virus vaccine><immune system response><immunogen><immunogenicity><immunologic assay><immunologic assay/test><immunoresponse><in vitro testing><mAbs><mRNA><mRNA vaccine><mRNA-based vaccine><membrane structure><nCoV><nCoV2><neutralizing antibody><new CoV><new corona virus><new coronavirus><novel CoV><novel corona virus><novel coronavirus><protein blotting><protein protein interaction><success><vaccine against 2019-nCov><vaccine against SARS-CoV-2><vaccine against SARS-CoV2><vaccine against SARS-coronavirus-2><vaccine against Severe Acute Respiratory Syndrome CoV 2><vaccine against Severe acute respiratory syndrome coronavirus 2><vaccine for novel coronavirus><vaccine platform><vaccine strategy><viral assembly><virus-like nanoparticles><viruslike particle>