Document text
Principal Investigator: Guido Ferrari
Organization: DUKE UNIVERSITY
Fiscal Year: 2023
Award: $5,902,563
Funding agency: National Institute of Allergy and Infectious Diseases
ABSTRACT
The ultimate goal of the proposed studies is to contribute to ending the HIV/AIDS epidemic. It has been
four decades since the start of the HIV/AIDS epidemic and a protective vaccine or functional cure has been
elusive. In 2020, there was an estimated 37.6 million people living with HIV. Despite highly active anti-retroviral
therapies, hundreds of thousands of people still die from AIDS-related diseases and millions of new infections
continue to emerge. Thus, finding a way to end this pandemic remains a global priority.
The overall goal of the Consortium for Innovative HIV/AIDS Vaccine and Cure Research (CIAVCR) is
to develop an effective combined immunotherapeutic regimen for HIV-1 prevention and cure using the non-
human primate (NHP) model that has a direct path to the clinic for use in humans. There are two FOCI
proposed in the CIAVCR: In FOCUS 1, our overall goal is to demonstrate the correlates and mechanisms of
protection for a protective vaccine, and the role of vaccine-induced immune responses in selecting and limiting
the latent reservoir. The benefits of using novel mRNA constructs to deliver immunogens that can elicit both
humoral and cellular responses will be evaluated. In FOCUS 2, our overall goal is to determine the role of
vaccine-induced immune responses to 1) control HIV-1 infection by reducing the size or eliminating HIV-1
reservoirs, and/or 2) delay plasma virus load rebound. The protective vaccines studied in FOCUS 1 will be
tested to define the mechanisms of vaccine-induced B and T cell responses in clearing HIV-1 reservoirs.
Additionally, novel therapies will be combined with the vaccines to augment clearance of HIV-1 reservoirs.
In both FOCUS 1 and 2, analysis of the breakthrough and latent reservoir Env sequences will inform the
design of new vaccine boosts for an improved protective vaccine regimen that can also limit rebound
viruses.
The NHP-SHIV Centralized Research Resource (CRR) will support the NHP studies in FOCUS 1 and
2 to investigate the effectiveness of vaccine-induced polyfunctional responses and novel immunotherapies
in clearing HIV-1 reservoirs. These studies will use innovative barcoded-SHIVs to determine the effect of
vaccine-induced responses on eliminating the viral reservoirs, and to evaluate the quantity and quality of
viruses that are reactivated by latency reversing agents (LRAs) following treatment interruption.
The Management and Operations Support Unit (MOS) will coordinate the scientific and
administrative activities of this CIAVCR Program to ensure that the FOCI and NHP-SHIV CRR function
cohesively.
By the end of this grant, we expect to have designed a combined preventive and therapeutic approach to
effectively protect from infection and eliminate viral reservoirs—a strategy for effectively impacting the HIV/AIDS
pandemic.
Terms: <7S Gamma Globulin><AIDS><AIDS Virus><Ab-dependent cellular cytotoxicity><Ab-mediated immunity><Ab-mediated protection><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><Animal Model><Animal Models and Related Studies><Animals><Antibody Response><Antibody immunity><Antibody protection><Antibody-mediated protection><Antigens><Approaches to prevention><Autologous><B blood cells><B cell><B cells><B-Cells><B-Lymphocytes><B-cell><Bar Codes><Binding><Blood Plasma><CD8 Cell><CD8 T cells><CD8 lymphocyte><CD8+ T cell><CD8+ T-Lymphocyte><CD8-Positive Lymphocytes><CD8-Positive T-Lymphocytes><COVID crisis><COVID epidemic><COVID pandemic><COVID-19 crisis><COVID-19 epidemic><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 pandemic><COVID-19 prevention><COVID-19 public health crisis><COVID19 crisis><COVID19 epidemic><COVID19 global health crisis><COVID19 global pandemic><COVID19 health crisis><COVID19 pandemic><COVID19 prevention><COVID19 public health crisis><Characteristics><Clinic><Clinical Research><Clinical Study><Clinical Treatment><Clinical Treatment Moab><Collaborations><Complex><Cytotoxic cell><Data><Development><Diagnosis><Disease><Disorder><Epidemic><Generations><Goals><Grant><HAART><HIV><HIV Infections><HIV vaccine><HIV-1><HIV-I><HIV/AIDS Vaccines><HIV1><HTLV-III Infections><HTLV-III-LAV Infections><Health Priorities><Highly Active Antiretroviral Therapy><Human><Human Immunodeficiency Virus Type 1><Human Immunodeficiency Viruses><Human T-Lymphotropic Virus Type III Infections><Human immunodeficiency virus 1><IgG><Immune mediated therapy><Immune response><Immunity><Immunoglobulin G><Immunological response><Immunologically Directed Therapy><Immunology><Immunotherapeutic agent><Immunotherapy><Infection><Infusion><Infusion procedures><Interruption><Investigators><K lymphocyte><LAV-HTLV-III><Licensing><Lymphadenopathy-Associated Virus><Messenger RNA><Modeling><Modern Man><Molecular Interaction><Monoclonal Antibodies><NK Cells><Natural Killer Cells><Outcome><Peptides><Persons><Plasma><Plasma Serum><Prevention><Prevention approach><Preventive><Process><RNA vaccine><RNA-based vaccine><Recombinants><Regimen><Research><Research Personnel><Research Resources><Researchers><Resources><Reticuloendothelial System, Serum, Plasma><Role><SARS-CoV-2 epidemic><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 pandemic><SARS-CoV2 epidemic><SARS-CoV2 pandemic><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><SEQ-AN><SHIV><Sampling><Sequence Analyses><Sequence Analysis><Severe Acute Respiratory Syndrome CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 pandemic><T cell response><T-Cells><T-Lymphocyte><T8 Cells><T8 Lymphocytes><Testing><Therapeutic><Universities><Vaccines><Variant><Variation><Viral Diseases><Viral load measurement><Viral reservoir><Virus><Virus Diseases><Virus Replication><Virus reservoir><Virus-HIV><anti-retroviral therapy><anti-retroviral treatment><antibody dependent cell mediated cytotoxicity><antibody dependent cytotoxicity><antibody mediated cellular cytotoxicity><antibody-dependent cell cytotoxicity><antibody-dependent cellular cytotoxicity><antibody-mediated cytotoxicity><antibody-mediated immunity><antiretroviral therapy><antiretroviral treatment><barcode><corona virus disease 2019 epidemic><corona virus disease 2019 pandemic><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 pandemic><coronavirus disease 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vivo><infusions><innovate><innovation><innovative><insight><latent HIV reservoir><latent HIV-1 reservoir><latent HIV1 reservoir><mAbs><mRNA><mRNA vaccine><mRNA-based vaccine><model of animal><monoclonal Abs><nano particle><nano-sized particle><nanoparticle><nanosized particle><neutralizing antibody><neutralizing mAb><neutralizing monoclonal antibodies><new approaches><new drug treatments><new drugs><new pharmacological therapeutic><new therapeutics><new therapy><new vaccines><next generation therapeutics><next generation vaccines><non-human primate><nonhuman primate><novel><novel approaches><novel drug treatments><novel drugs><novel pharmaco-therapeutic><novel pharmacological therapeutic><novel strategies><novel strategy><novel therapeutics><novel therapy><novel vaccines><operation><operations><pandemic><pandemic disease><pre-clinical><preclinical><prevent><prevent COVID-19><prevent COVID19><prevent coronavirus disease 2019><preventing><programs><response><severe acute respiratory 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