Saman Eskandarzadeh
A5042583739- HIV Research and Treatment
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Immunodeficiency and Autoimmune Disorders
- Monoclonal and Polyclonal Antibodies Research
- SARS-CoV-2 and COVID-19 Research
- Ginseng Biological Effects and Applications
- Herpesvirus Infections and Treatments
- RNA Interference and Gene Delivery
- Toxin Mechanisms and Immunotoxins
- Blood groups and transfusion
- Cytomegalovirus and herpesvirus research
- vaccines and immunoinformatics approaches
Scripps Research Institute
2022-2025
International AIDS Vaccine Initiative
2022-2024
Ragon Institute of MGH, MIT and Harvard
2024
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
Vaccines generate high-affinity antibodies by recruiting antigen-specific B cells to germinal centers (GCs), but the mechanisms governing recruitment GCs on secondary challenges remain unclear. Here, using preclinical SARS-CoV and HIV mouse models, we demonstrated that elicited during primary humoral responses shaped naive cell exposures. The from could either enhance or, conversely, restrict GC participation of cells: broad-binding, low-affinity, low-titer enhanced recruitment, whereas,...
Abstract A key barrier to the development of vaccines that induce broadly neutralizing antibodies (bnAbs) against human immunodeficiency virus (HIV) and other viruses high antigenic diversity is design priming immunogens rare bnAb-precursor B cells. The neutralization breadth HIV bnAb 10E8 makes elicitation 10E8-class bnAbs desirable; however, recessed epitope within gp41 envelope trimers poor requires possess a long heavy chain complementarity determining region 3 (HCDR3) with specific...
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...
Germline-targeting (GT) protein immunogens to induce VRC01-class broadly neutralizing antibodies (bnAbs) the CD4-binding site of HIV envelope (Env) have shown promise in clinical trials. Here, we preclinically validated a lipid nanoparticle-encapsulated nucleoside mRNA (mRNA-LNP) encoding eOD-GT8 60mer as soluble self-assembling nanoparticle mouse models. In model with three humanized B cell lineages bearing distinct VRC01-precursor receptors (BCRs) similar affinities for eOD-GT8, all could...
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 Adjuvants and antigen delivery kinetics can profoundly influence B cell responses should be critically considered in rational vaccine design, particularly for difficult neutralizing antibody targets such as human immunodeficiency virus (HIV). Antigen change depending on the method. To promote extended immunogen bioavailability to present a multivalent form, native-HIV Env trimers are modified with short phosphoserine peptide linkers that tight binding aluminum hydroxide (pSer:alum)....
SUMMARY Saponin-based vaccine adjuvants are potent in preclinical animal models and humans, but their mechanisms of action remain poorly understood. Here, using a stabilized HIV envelope trimer immunogen, we carried out studies non-human primates (NHPs) comparing the most common clinical adjuvant alum with Saponin/MPLA Nanoparticles (SMNP), novel ISCOMs-like adjuvant. SMNP elicited substantially stronger humoral immune responses than alum, including 7-fold higher peak antigen-specific...
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...
Abstract Saponin-based vaccine adjuvants are potent in preclinical animal models and humans, but their mechanisms of action remain poorly understood. Here, using a stabilized HIV envelope trimer immunogen, we carried out studies nonhuman primates (NHPs) comparing the most common clinical adjuvant aluminum hydroxide (alum) with saponin/monophosphoryl lipid A nanoparticles (SMNP), an immune-stimulating complex–like adjuvant. SMNP elicited substantially stronger humoral immune responses than...