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Principal Investigator: Kristina De Paris
Organization: WEILL MEDICAL COLL OF CORNELL UNIV
Fiscal Year: 2024
Award: $1,370,057
Funding agency: National Institute of Allergy and Infectious Diseases
ABSTRACT – Overall
Nearly 600,000 new HIV infections occur yearly in adolescents/young adults (ages 15-24 years), the only
population in which HIV infections continue to rise. The end of the HIV/AIDS epidemic will be achievable only
when an effective vaccine regimen can elicit long-term protective immunity in preadolescence, prior to sexual
debut. Yet, even the most promising HIV envelope (Env) vaccine platforms have failed to induce highly-
protective immunity in adults in preclinical and clinical studies. Interestingly, recent studies indicate that
durable, polyfunctional, and broad neutralizing antibody (bnAb) responses following HIV infection occur more
frequently and are equal or more potent in infants compared to that of adults. Yet, there remains a gap in our
understanding of the immunologic mechanisms associated with the rapid induction of HIV bnAb and effector
antibody functions within the infant immune landscape.
The overall goal of this HIVRAD renewal is to harness the unique qualities of the early life immune system for
vaccine elicitation of protective HIV immunity. This work builds on our current HIVRAD Program focusing on
the development of HIV Env vaccine regimens for prevention of infant HIV acquisition. We defined the optimal
vaccine intervals, adjuvants, and doses to achieve maximal immunogenicity in the infant immune system, and
determined that concurrent passive bnAb-active HIV Env immunization does not impair vaccine-elicited
immune responses. In this renewal HIVRAD Program, we hypothesize that HIV Env vaccine platforms
administered in early life and boosted in preadolescence will achieve more durable, broad, and polyfunctional
immune responses and be more efficacious at prevention of sexual transmission than initiation of immunization
in preadolescence. We will compare vaccine responses to two of the most promising HIV Env vaccine
candidates, bnAb germline-targeting SOSIP trimers (Project 1) and lipid nanoparticle mRNA vaccines (Project
2) initiated in infancy with boosting throughout childhood to that of initiation of vaccination in preadolescence in
the rhesus model (Nonhuman Primate (NHP) Core), and test their efficacy against intrarectal homologous
and heterologous SHIV challenge in adolescence. We will apply systems immunology to define the
immunologic, transcriptomic, and microbiologic signatures associated with the HIV Env vaccine antibody
function and induction of bnAb precursors (Integrated Systems Immunology Core (ISIC)). The
Administrative Core provides the full range of support for scientific, fiscal, and other programmatic
management and oversight. By leveraging the extended window for maturation of vaccine-induced responses
and defining the mechanistic advantages of early life immunization for effective anti-HIV responses, this
Program will inform the target population and design of an HIV Env vaccine that will provide life-long
protection.
Terms: <12-20 years old><21+ years old><AIDS Virus><AIDS/HIV><Ab-mediated immunity><Ab-mediated protection><Achievement><Achievement Attainment><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome Virus><Adjuvant><Adolescence><Adolescent><Adolescent Youth><Adult><Adult Human><Adult females><Adult women><Age><Antibodies><Antibody Response><Antibody immunity><Antibody protection><Antibody-mediated protection><Antigens><Autologous><B blood cells><B cell><B cells><B-Cells><B-Lymphocytes><B-cell><Biological><Blood Plasma><Breast Milk><Breastmilk><Cell Body><Cell Communication><Cell Interaction><Cell Lineage><Cell-to-Cell Interaction><Cells><Childhood><Clinical Research><Clinical Study><Collaborations><Development><Dose><Epidemic><Evolution><Females in adulthood><Funding><Future><Germ Lines><Goals><HIV><HIV Infections><HIV envelope><HIV envelope protein><HIV vaccine><HIV-1><HIV-I><HIV/AIDS><HIV/AIDS Vaccines><HIV1><HTLV-III Infections><HTLV-III-LAV Infections><Human><Human Immunodeficiency Virus Type 1><Human Immunodeficiency Viruses><Human Milk><Human Mother's Milk><Human T-Lymphotropic Virus Type III Infections><Human immunodeficiency virus 1><Ig Somatic Hypermutation><Immune><Immune response><Immune system><Immunes><Immunity><Immunization><Immunize><Immunochemical Immunologic><Immunoglobulin Somatic Hypermutation><Immunologic><Immunological><Immunological response><Immunologically><Immunologics><Immunology><Infant><Infection><Infrastructure><LAV-HTLV-III><Life><Lymphadenopathy-Associated Virus><M mulatta><M. mulatta><Macaca mulatta><Mammary Gland Milk><Mediating><Messenger RNA><Modeling><Modern Man><Molecular><Monkeys><Mother's Milk><Passive Immunization><Pathway interactions><Plasma><Plasma Serum><Population><Prevention><RNA vaccine><RNA-based vaccine><Rectum><Regimen><Reticuloendothelial System, Serum, Plasma><Rhesus><Rhesus Macaque><Rhesus Monkey><Risk Reduction><SHIV><Sexual Transmission><System><Systems Biology><Target Populations><Testing><Time><Translations><Transmission><Vaccination><Vaccine Clinical Trial><Vaccine Design><Vaccines><Vertical Disease Transmission><Virus><Virus-HIV><Women in adulthood><Work><Youth><Youth 10-21><adolescence (12-20)><adult youth><adulthood><age group><ages><antibody-mediated immunity><biologic><design><designing><developmental><global gene expression><global transcription profile><host response><human immunodeficiency virus vaccine><immune response to vaccination><immune response to vaccines><immune system response><immunization strategy><immunogen><immunogenicity><immunoresponse><infancy><infantile><initiation of sexual activity><insight><juvenile><juvenile human><lipid based nanoparticle><lipid nanoparticle><mRNA><mRNA lipid nano particle vaccine><mRNA vaccine><mRNA-LNP based vaccine><mRNA-LNP combination vaccines><mRNA-LNP vaccines><mRNA-based vaccine><maternal milk><microbial><microbial consortia><microbial flora><microbial interaction><microbial signature><microbiome><microbiota><microflora><microorganism interaction><mother to child transmission><multispecies consortia><neutralizing antibody><non-human primate><nonhuman primate><novel><passive vaccination><pathway><pediatric><pre-adolescent><pre-clinical study><preadolescence><preclinical study><predictive signature><preteen><prevent><preventing><programs><reduce risk><reduce risks><reduce that risk><reduce the risk><reduce these risks><reduces risk><reduces the risk><reducing risk><reducing the risk><response><risk-reducing><sexual debut><sexual initiation><sexually transmitted><simian HIV><simian human immunodeficiency virus><somatic hypermutation><transcriptome><transcriptomics><translation><transmission process><vaccination strategy><vaccine antibodies><vaccine associated immune response><vaccine candidate><vaccine immune response><vaccine immunogenicity><vaccine induced antibodies><vaccine induced immune response><vaccine platform><vaccine response><vaccine responsiveness><vaccine strategy><vaccine-induced antibodies><vaccine-induced response><young adult><young adulthood>