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Principal Investigator: Yang Xu
Organization: LUNA LABS USA, LLC
Fiscal Year: 2024
Award: $903,639
Funding agency: National Institute of Mental Health
Project Summary
Significant research has gone into the development of a safe and effective vaccine for HIV-1.
Although many strategies have been attempted; none has been successfully established. Even a
partially effective vaccine could decrease the number of people who are infected with HIV, further
reducing the number of people who can pass the virus on to others. By substantially reducing the
number of new infections, we could eventually stop the pandemic. To date, the elicitation of
broadly neutralizing antibodies (bNAbs) has proven extremely difficult to achieve which brought
a lot of effort on the novel trimer design and modification. At the same time, it was found that
induced HIV- specific CD8+ T cell responses could limit both the transmission and establishment
of persistent viral reservoirs. All the evidence suggest that no individual factor will determine the
ultimate success of a bNAb-inducing HIV-1 vaccine, which will likely require a combination of
efficient precursor B cell priming, optimization of Env design and presentation, sustained
heterologous Env boosting, a T cell-based strategy, and newly developed delivery systems or
adjuvants. Adjuvants or delivery systems can stimulate different arms of the immune system and
are vital components of subunit vaccines, especially in the case of poorly immunogenic envelope
glycoprotein. Deliver systems can also be designed to address instability of mRNA-based
vaccines. The goal of this program is therefore to overcome challenges with HIV-1 vaccination
and deliver a safe and effective vaccine using a biocompatible, biodegradable, easily
manufactured short carbon nanotube (CNTVac) platform. Env-trimer and mRNA encoding
peptide will be antigens for delivery and will target generation of both humoral and cellular
responses. A humanized mouse model and a non-human primate model will be used for
immunogenicity and efficacy studies. As the novel non-viral gene transfer vector for HIV-1 vaccine
delivery, we will establish methodology for potential GMP production and generate safety profiles
under FDA requirements.
Terms: <ADME Study><AIDS Virus><Absorption, Distribution, Metabolism, and Excretion Study><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome Virus><Address><Adjuvant><Affinity><Antibodies><Antigen Variation><Antigenic Determinants><Antigenic Variability><Antigenic Variation><Antigens><B blood cells><B cell><B cells><B-Cells><B-Lymphocytes><B-cell><Binding><Binding Determinants><Biotech><Biotechnology><Buckytubes><CD8><CD8 Cell><CD8 T cells><CD8 lymphocyte><CD8+ T cell><CD8+ T-Lymphocyte><CD8-Positive Lymphocytes><CD8-Positive T-Lymphocytes><CD8B><CD8B1><CD8B1 gene><Carbon Nanotubes><Carbon nano tubes><Certification><Chemistry><Clinical><Clinical Research><Clinical Study><Collaborations><Development><Ensure><Epitopes><Formulation><Generations><Glycans><Glycoproteins><Goals><HIV><HIV resistance><HIV resistant><HIV vaccine><HIV-1><HIV-1 vaccine><HIV-I><HIV/AIDS Vaccines><HIV1><HIV1 vaccine><Human Immunodeficiency Virus Type 1><Human Immunodeficiency Viruses><Human immunodeficiency virus 1><Immune response><Immune system><Immunological response><In Vitro><Individual><Infection><Injectable><Injections><Intramuscular><LAV-HTLV-III><LYT3><Lymphadenopathy-Associated Virus><M mulatta><M. mulatta><Macaca mulatta><Mediating><Messenger RNA><Methodology><Methods><Modeling><Modification><Molecular Configuration><Molecular Conformation><Molecular Interaction><Molecular Stereochemistry><Peptides><Persons><Phase><Physiologic><Physiological><Polysaccharides><Pre IND FDA meeting><Pre-IND mtg><Process><Production><RNA vaccine><RNA-based vaccine><Radiolabeled><Recombinants><Research><Retroviridae><Retroviruses><Rhesus Macaque><Rhesus Monkey><Safety><Specific qualifier value><Specified><Structure><Subunit Vaccines><Surface><Synthetic Antigens><System><T cell response><T-Cells><T-Lymphocyte><T8 Cells><T8 Lymphocytes><Technology><Testing><Time><Toxic effect><Toxicities><Translations><Transmission><Universities><Vaccination><Vaccines><Validation><Viral reservoir><Virus><Virus reservoir><Virus-HIV><Virus-Retrovirus><Work><analytical method><arm><biocompatibility><biomaterial compatibility><clinical translation><clinically translatable><commercial scale manufacturing><conformation><conformational><conformational state><conformationally><conformations><cost><cost effective><deliver mRNA><deliver messenger RNA><deliver vaccines><delivery system for mRNA><design><designing><develop a vaccine><develop vaccines><development of a vaccine><developmental><discover vaccines><efficacy study><gang><gene transfer vector><host response><human immunodeficiency virus vaccine><humanized mice><humanized mouse><immune system response><immunogen><immunogenic><immunogenicity><immunoresponse><in vivo><lipid based nanoparticle><lipid nanoparticle><mRNA><mRNA Instability><mRNA delivery><mRNA vaccine><mRNA-based vaccine><manufacture><manufacturing process><manufacturing ramp-up><manufacturing scale-up><messenger RNA delivery><mouse model><murine model><nano vaccine><nanovaccine><neutralizing antibody><non-human primate><nonhuman primate><novel><pandemic><pandemic disease><pre-IND consultation><pre-IND discussion><pre-IND meeting><pre-Investigational New Drug meeting><pre-clinical study><preclinical study><predict responsiveness><predicting response><preservation><programs><radiolabeling><radiologically labeled><response><scale up><scale up batch><scale up production><success><thymus derived lymphocyte><translation><transmission process><upscale manufacturing><vaccine candidate><vaccine delivery><vaccine development><vaccine discovery><vaccine formulation><vaccine platform><validations>