Nushin Alavi
A5063437170- HIV Research and Treatment
- Immunodeficiency and Autoimmune Disorders
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- vaccines and immunoinformatics approaches
- Bacteriophages and microbial interactions
- RNA Interference and Gene Delivery
- Immune Cell Function and Interaction
- Blood groups and transfusion
- Hepatitis B Virus Studies
- Cytomegalovirus and herpesvirus research
- Vaccine Coverage and Hesitancy
International AIDS Vaccine Initiative
2022-2025
Scripps Research Institute
2022-2025
Broadly neutralizing antibodies (bnAbs) can protect against HIV infection but have not been induced by human vaccination. A key barrier to bnAb induction is vaccine priming of rare bnAb-precursor B cells. In a randomized, double-blind, placebo-controlled phase 1 clinical trial, the vaccine-priming candidate eOD-GT8 60mer adjuvanted with AS01
Broadly neutralizing antibodies (bnAbs) to the HIV envelope (Env) V2-apex region are important leads for vaccine design. Most bnAbs engage Env with an uncommonly long heavy-chain complementarity-determining 3 (HCDR3), suggesting that rarity of bnAb precursors poses a challenge priming. We created precursor sequence definitions HCDR3-dependent and searched related in human antibody ultradeep sequencing data from 14 HIV-unexposed donors. found potential majority donors only two long-HCDR3...
A protective HIV vaccine will likely need to induce broadly neutralizing antibodies (bnAbs). Vaccination with the germline-targeting immunogen eOD-GT8 60mer adjuvanted AS01
A protective vaccine against HIV will likely need to induce broadly neutralizing antibodies (bnAbs) that engage relatively conserved epitopes on the envelope glycoprotein (Env) trimer. Nearly all strategies bnAbs require use of complex immunization regimens involving a series different immunogens, most which are Env trimers. Producing protein-based clinical material evaluate such in humans presents major challenges cost and time. Furthermore, with trimers as soluble proteins induces strong...
Abstract Transmembrane glycoproteins of enveloped viruses are the targets neutralizing antibodies and essential vaccine antigens. mRNA-LNP technology allows in situ production transmembrane upon immunization, but biophysical characterization antigens vitro analysis post-immunization antibody responses typically rely on soluble proteins. Here, we present a methodological platform for assembling glycoprotein candidates into lipid nanodiscs. We demonstrate utility nanodiscs HIV membrane...
One challenge in vaccine development is designing immunogens that elicit durable immunity. We hypothesized antigen avidity regulates the magnitude, diversity, and durability of immune response. tested this multiple preclinical HIV models using a neoteric mosaic nanoparticle platform. This allowed us to precisely modulate by varying multivalency affinity independently, whilst keeping other variables constant. Antigen drove seeding, interclonal competition, immunodominance within germinal...
A leading HIV vaccine strategy requires a priming immunogen to induce broadly neutralizing antibody (bnAb) precursors, followed by series of heterologous boosters elicit somatic hypermutation (SHM) and produce bnAbs. In two randomized, open-label phase 1 human clinical trials, IAVI-G002 in the United States IAVI-G003 Rwanda South Africa, we evaluated safety immunogenicity mRNA-encoded nanoparticles as immunogens (both trials) first-boosting (IAVI-G002). The vaccines were generally safe well...
SUMMARY Rare B cells can have special pathogen-recognition features giving them the potential to make outsized contributions protective immunity. However, rare naive infrequently participate in immune responses. We investigated how germline-targeting vaccine antigen delivery and adjuvant selection affect priming of exceptionally BG18-like HIV broadly neutralizing antibody-precursor (~1 50 million) non-human primates. Only escalating dose (ED) immunization using saponin SMNP elicited...