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Principal Investigator: JOHN D. AITCHISON
Organization: INTERNATIONAL AIDS VACCINE INITIATIVE
Fiscal Year: 2020
Award: $451,361
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY (Core C - Gene Expression Signatures)
HIV has proven its ability to defeat all vaccine candidates tested to date. However, evidence in humans and
model systems demonstrates that immune system is capable of generating antibodies that neutralize multiple
HIV-1 viral strains. While the mechanisms that lead to the generation of broadly neutralizing antibodies remain
to be determined, a number of studies have shown that the early innate immune responses to vaccines are
predictive of the subsequent adaptive response which is responsible for protection. Thus, transcriptional
signatures of innate responses can be used to discover gene regulatory networks, or “rules”, driving adaptive
responses and vaccine efficacy. In this program we seek to comprehensively evaluate, and compare 4 novel
vaccines that deliver a common HIV immunogen, but differ in their mode of delivery and their potential
immunostimulatory profiles. We will use early transcriptional signatures (gene signatures) as part of this
program to reveal the innate immune networks elicited by each vaccine candidate and delivery strategy, to
correlate vaccine elicited immunogenicity with early innate immune signatures, to provide a framework for
predicting the efficacy of vaccine candidates, and to lay a foundation for future rational vaccine designed to
activate desired innate immune responses and subsequent adaptive responses.
Terms: <AIDS Virus><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome Virus><Adjuvant><Animals><Antigens><Area><Automobile Driving><Biologic Models><Biological Models><Biological Response Modifiers><Biomodulators><Blood><Blood Reticuloendothelial System><Collaborations><Computing Methodologies><Data><Domestic Rabbit><Event><Expression Profiling><Expression Signature><Foundations><Functional RNA><Future><Gene Cluster><Gene Expression><Gene Expression Monitoring><Gene Expression Pattern Analysis><Gene Expression Profile><Gene Expression Profiling><Generations><Genes><HIV><HIV-1><HIV-I><HIV1><Human><Human Immunodeficiency Virus Type 1><Human Immunodeficiency Viruses><Human immunodeficiency virus 1><Immune><Immune Mediators><Immune Mediators/Modulators><Immune Regulators><Immune system><Immunes><Immunochemical Immunologic><Immunologic><Immunological><Immunologically><Immunologics><Immunology procedure><Immunomodulation><Infectious Diseases / Laboratory><Infectious Diseases Research><Inflammatory Response><Innate Immune Response><Innate Immune System><Innate Immunity><Intuition><LAV-HTLV-III><Lead><Link><Lymphadenopathy-Associated Virus><Macaca><Macaque><Machine Learning><Messenger RNA><Mice><Mice Mammals><Model System><Modeling><Modern Man><Murine><Mus><Native Immunity><Natural Immunity><Network Analysis><Non-Coding><Non-Coding RNA><Non-Specific Immunity><Non-translated RNA><Noncoding RNA><Nonspecific Immunity><Nontranslated RNA><Oryctolagus cuniculus><Outcome><Pathway Analysis><Pathway interactions><Pattern><Pb element><Process><RNA Seq><RNA Splicing><RNA sequencing><RNAseq><Rabbits><Rabbits Mammals><Regimen><Regulator Genes><Sampling><Splicing><Systems Biology><Testing><Transcript><Transcript Expression Analyses><Transcript Expression Analysis><Transcriptional Regulatory Elements><Untranslated RNA><Vaccinated><Vaccination><Vaccine Design><Vaccines><Veins><Viral><Virus-HIV><Visualization><adaptive immune response><allergic/immunologic body system><allergic/immunologic organ system><base><computational methodology><computational methods><computer based method><computer methods><computing method><data reduction><data visualization><discover genes><draining lymph node><driving><experience><feature selection><flexibility><flexible><gene discovery><gene expression analysis><gene expression assay><gene expression pattern><gene expression signature><gene signatures><genetic signature><heavy metal Pb><heavy metal lead><high dimensional data><high throughput technology><immune modulation><immune regulation><immune regulator><immunogen><immunogenicity><immunologic assay><immunologic assay/test><immunologic reactivity control><immunomodulatory><immunomodulatory biologics><immunoregulation><immunoregulatory><large scale data><large scale data sets><large scale datasets><mRNA><machine learned><multidimensional data><multidimensional datasets><neutralizing antibody><new vaccines><next generation vaccines><noncoding><novel><novel vaccines><outcome prediction><pathway><predictive outcomes><predictors of outcomes><programs><regional lymph node><regulatory gene><response><trans acting element><transcriptional profiling><transcriptional signature><transcriptome sequencing><transcriptomics><vaccination strategy><vaccine candidate><vaccine delivery><vaccine efficacy>