Recombinant Vaccines for Prevention of AIDS and Other Diseases
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Principal Investigator: Bernard Moss Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES Fiscal Year: 2020 Award: $1,341,664 Funding agency: National Institute of Allergy and Infectious Diseases There are many diseases for which there are no vaccines and others for which the vaccines are not optimal or have significant side effects. The objectives of this project are to develop new vectors, characterize viral antigens, determine targets of humoral and cell mediated immunity, and use this information to develop candidate vaccines. Live recombinant viral vaccines, DNA vaccines and recombinant protein vaccines are being developed. Presently we are working on vaccinia virus-vectored vaccines for HIV and SARS CoV-2. The vaccines are first tested in small animals and then in non-human primates. Phase 1 and 2 clinical trials with MVA-vectored vaccines developed in our laboratory are ongoing by collaborators. The vaccines were safe and immunogenic. Animal studies revealed good boosting of MVA primed immunizations with gp140 and trimeric gp120 proteins and with virus-like particles. In the current year we have been working on the highly attenuated vaccine vector MVA, which is an approved smallpox vaccine and is undergoing clinical trials as a vaccine vector for other infectious diseases. Although an inability to replicate in human cells contributes to the safety of MVA, the basis for its host restriction is not understood. We identified a new host-range gene C16L/B22R, which is present as two copies in most orthopoxviruses but is inactivated in MVA. Repair of this gene allows replication of MVA in several tested human cell lines and in combination with a second missing host range gene C12L that we described last year restores full replication. Furthermore, a human cell line expressing both proteins is permissive for MVA. This knowledge may contribute to further engineering of MVA vaccines. As an adjunct to this project we carried out a human genome-wide siRNA screen and have identified the host target of the protein encoded by the C16L gene. The current SARS CoV-2 pandemic has led us to prepare recombinant MVAs expressing modifiied forms of the spike protein. Thus far we have shown that these constructs are immunogenic and further testing is in progress Terms: <2019 novel coronavirus><2019-nCoV><AIDS><AIDS Virus><Acquired Immune Deficiency><Acquired Immune Deficiency Syndrome><Acquired Immune Deficiency Syndrome Virus><Acquired Immuno-Deficiency Syndrome><Acquired Immunodeficiency Syndrome><Acquired Immunodeficiency Syndrome Virus><Acquired Immunologic Deficiency Syndrome><Animals><Antigens><Attenuated Vaccines><Cell Body><Cell Mediated Immunology><Cell-Mediated Immunity><Cells><Cellular Immunity><Clinical Trials><Communicable Diseases><DNA Vaccines><Disease><Disorder><Early-Stage Clinical Trials><Genes><HIV><HIV Envelope Glycoprotein gp120><HIV Envelope Protein gp120><HIV env Protein gp120><HIV vaccine><HIV/AIDS Vaccines><HTLV-III gp120><Human><Human Cell Line><Human Genome><Human Immunodeficiency Viruses><Immunization><Immunologic Sensitization><Immunologic Stimulation><Immunological Sensitization><Immunological Stimulation><Immunostimulation><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><Knowledge><LAV-HTLV-III><Laboratories><Lymphadenopathy-Associated Virus><Modern Man><Naked DNA Vaccines><Orthopox virus><Orthopoxvirus><Phase 1 Clinical Trials><Phase 2 Clinical Trials><Phase I Clinical Trials><Phase II Clinical Trials><Poxviridae><Poxviruses><Prevention><Proteins><Recombinant DNA Vaccines><Recombinant Proteins><Recombinant Vaccines><Recombinant Viral Vaccine><Recombinant modified vaccinia virus Ankara><Research><SARS-CoV-2><SARS-CoV2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related coronavirus 2><Safety><Severe acute respiratory syndrome coronavirus 2><Short interfering RNA><Small Interfering RNA><Smallpox Vaccine><Testing><Vaccines><Viral><Viral Antigens><Viral Vector><Virus-HIV><Virus-like particle><Wuhan coronavirus><engineered MVA><gene repair><genome scale><genome-wide><genomewide><gp120><gp120 ENV Glycoprotein><gp120(HIV)><human immunodeficiency virus vaccine><human whole genome><immunogen><immunogenic><improved><live vaccine><non-human primate><nonhuman primate><pandemic><pandemic disease><phase I protocol><phase II protocol><plasmid vaccine><pox virus><rMVA><recombinant MVA><recombinant virus vaccine><siRNA><side effect><small pox vaccine><vaccine candidate><vaccinia vector><vaccinia virus vector><vector><vector vaccine><virus antigen><virus-like nanoparticles><viruslike particle>