Jelle van Schooten
A5080717638- HIV Research and Treatment
- Monoclonal and Polyclonal Antibodies Research
- SARS-CoV-2 and COVID-19 Research
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- COVID-19 Clinical Research Studies
- Glycosylation and Glycoproteins Research
- SARS-CoV-2 detection and testing
- COVID-19 epidemiological studies
- Animal Virus Infections Studies
- T-cell and B-cell Immunology
- Herpesvirus Infections and Treatments
- Viral gastroenteritis research and epidemiology
- Vaccine Coverage and Hesitancy
- interferon and immune responses
- HIV-related health complications and treatments
- Escherichia coli research studies
- Cytomegalovirus and herpesvirus research
- Viral Infections and Outbreaks Research
- HIV/AIDS Research and Interventions
- HIV/AIDS drug development and treatment
University of Amsterdam
2018-2024
Amsterdam University Medical Centers
2018-2024
Amsterdam UMC Location University of Amsterdam
2023-2024
California Institute of Technology
2018-2023
National Institute of Allergy and Infectious Diseases
2018
Sites of vulnerability in SARS-CoV-2 Antibodies that neutralize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could be an important tool treating disease 2019 (COVID-19). Brouwer et al. isolated 403 monoclonal antibodies from three convalescent COVID-19 patients. They show the patients had strong immune responses against viral spike protein, a complex binds to receptors on host cell. A subset was able virus. Competition and electron microscopy studies showed these target...
Most antibodies isolated from individuals with coronavirus disease 2019 (COVID-19) are specific to severe acute respiratory syndrome 2 (SARS-CoV-2). However, COVA1-16 is a relatively rare antibody that also cross-neutralizes SARS-CoV. Here, we determined crystal structure of the fragment (Fab) SARS-CoV-2 receptor-binding domain (RBD) and negative-stain electron microscopy reconstructions spike glycoprotein trimer elucidate structural basis its cross-reactivity. binds highly conserved epitope...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is continuing to disrupt personal lives, global healthcare systems, and economies. Hence, there an urgent need for a vaccine that prevents viral infection, transmission, disease. Here, we present two-component protein-based nanoparticle displays multiple copies of the SARS-CoV-2 spike protein. Immunization studies show this induces potent neutralizing antibody responses in mice, rabbits, cynomolgus macaques....
The induction of broad and potent immunity by vaccines is the key focus research efforts aimed at protecting against HIV-1 infection. Soluble native-like envelope glycoproteins have shown promise as vaccine candidates they can induce autologous neutralizing responses in rabbits non-human primates. In this study, monoclonal antibodies were isolated characterized from rhesus macaques immunized with BG505 SOSIP.664 trimer to better understand vaccine-induced antibody responses. Our studies...
Abstract The rapid spread of SARS-CoV-2 has a significant impact on global health, travel and economy. Therefore, preventative therapeutic measures are urgently needed. Here, we isolated neutralizing antibodies from convalescent COVID-19 patients using stabilized prefusion spike protein. Several these were able to potently inhibit live infection at concentrations as low 0.007 µg/mL, making them the most potent human described date. Mapping studies revealed that protein contained multiple...
Abstract Effective treatments against Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) are urgently needed. Monoclonal antibodies have shown promising results in patients. Here, we evaluate the vivo prophylactic and therapeutic effect of COVA1-18, a neutralizing antibody highly potent B.1.1.7 isolate. In both settings, SARS-CoV-2 remains undetectable lungs treated hACE2 mice. Therapeutic treatment also causes reduction viral loads Syrian hamsters. When administered at 10 mg kg-1...
Eliciting potent and broadly neutralizing antibodies (bnAbs) is a major goal in HIV-1 vaccine development. Here, we describe how germline-targeting immunogen BG505 SOSIP germline trimer 1.1 (GT1.1), generated through structure-based design, engages diverse range of VRC01-class bnAb precursors. A single immunization with GT1.1 expands CD4 binding site (CD4bs)–specific B cells knock-in mice drives maturation. In nonhuman primates (NHPs), primes CD4bs-specific serum responses. Selected...
Adolescents are a growing population of people living with HIV. The period between weaning and sexual debut presents low-risk window for HIV acquisition, making early childhood an ideal time implementing immunization regimen. Because the elicitation broadly neutralizing antibodies (bnAbs) is critical effective vaccine, our goal was to assess ability bnAb B cell lineage-designed envelope SOSIP (protein stabilized by disulfide bond gp120-gp41-named "SOS"-and isoleucine-to-proline point...
Passive transfer of broadly neutralizing anti–HIV-1 antibodies (bNAbs) protects against infection, and therefore, eliciting bNAbs by vaccination is a major goal HIV-1 vaccine efforts. that target the CD4 binding site (CD4bs) on Env are among most active, but to date, responses elicited this epitope in vaccinated animals have lacked potency breadth. We hypothesized CD4bs resembling antibody IOMA might be easier elicit than other exhibit higher somatic mutation rates, difficult-to-achieve...
Most antibodies isolated from COVID-19 patients are specific to SARS-CoV-2. COVA1-16 is a relatively rare antibody that also cross-neutralizes SARS-CoV. Here we determined crystal structure of Fab with the SARS-CoV-2 RBD, and negative-stain EM reconstruction spike glycoprotein trimer, elucidate structural basis its cross-reactivity. binds highly conserved epitope on mainly through long CDR H3, competes ACE2 binding due steric hindrance rather than overlap. flexible up conformation RBD relies...
The development of an effective human immunodeficiency virus (HIV-1) vaccine is a high global health priority. Soluble native-like HIV-1 envelope glycoprotein trimers (Env), including those based on the SOSIP design, have shown promise as candidates by inducing neutralizing antibody responses against autologous in animal models. However, to overcome HIV-1's extreme diversity needs induce broadly antibodies (bNAbs). Such bNAbs can protect non-human primates (NHPs) and humans from infection....
Soluble "SOSIP"-stabilized envelope (Env) trimers are promising HIV-vaccine immunogens. However, they induce high-titer responses against the glycan-free trimer base, which is occluded on native virions. To delineate effect base of priming with immunogens targeting fusion peptide (FP) site vulnerability, here, we quantify prevalence trimer-base antibody in 49 non-human primates immunized various SOSIP-stabilized Env and FP-carrier conjugates. Trimer-base account for ∼90% overall response...
The human immunodeficiency virus type 1 (HIV-1) trimeric envelope glycoprotein (Env) is heavily glycosylated, creating a dense glycan shield that protects the underlying peptidic surface from antibody recognition. absence of conserved glycans, due to missing potential N-linked glycosylation sites (PNGS), can result in strain-specific, autologous neutralizing (NAb) responses. Here, we sought gain deeper understanding neutralization by introducing holes otherwise shields AMC011 and AMC016...
Abstract A major goal of current HIV-1 vaccine design efforts is to induce broadly neutralizing antibodies (bNAbs). The VH1-2-derived bNAb IOMA directed the CD4-binding site envelope glycoprotein interest because, unlike better-known VRC01-class bNAbs, it does not require a rare short light chain complementarity-determining region 3 (CDRL3). Here, we describe three IOMA-class NAbs, ACS101-103, with up 37% breadth, that share many characteristics IOMA, including an average-length CDRL3....
Background:The most effective way to control the AIDS epidemic would be through active vaccination.The current focus of HIV vaccine design is induction broadly neutralizing antibodies (bNAbs) against Envelope protein (Env) that neutralize majority circulating viral strains.Due their breadth and potency, desirable bNAbs elicit immunization are VRC01-class target conserved host receptor (CD4) binding site (CD4bs).VRC01-class mimic CD4 share a common mode gp120 glycan accommodation using...
<title>Abstract</title> One year into the Coronavirus Disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), effective treatments are still needed<sup>1–3</sup>. Monoclonal antibodies, given alone or as part of a therapeutic cocktail, have shown promising results in patients, raising hope that they could play an important role preventing clinical deterioration severely ill exposed, high risk individuals<sup>4–6</sup>. Here, we evaluated...
Abstract The induction of broad and potent immunity by vaccines is the key focus research efforts aimed at protecting against HIV-1 infection. Soluble native-like envelope glycoproteins have shown promise as vaccine candidates they can induce autologous neutralizing responses in rabbits non-human primates. In this study, monoclonal antibodies were isolated characterized from rhesus macaques immunized with BG505 SOSIP.664 trimer to better understand vaccine-induced antibody responses. Our...
Abstract The HIV-1 envelope glycoprotein (Env) trimer is the key target for vaccines aimed at inducing neutralizing antibodies (NAbs) against HIV-1. clinical candidate immunogen ConM SOSIP.v7 a stabilized native-like Env based on an artificial consensus sequence of all isolates in group M. In preclinical studies trimers induced strong autologous NAb responses non-human primates (NHPs). To fine-map these responses, we isolated monoclonal (mAbs) from six cynomolgus macaques that were immunized...
Summary The SARS-CoV-2 pandemic is continuing to disrupt personal lives, global healthcare systems and economies. Hence, there an urgent need for a vaccine that prevents viral infection, transmission disease. Here, we present two-component protein-based nanoparticle displays multiple copies of the spike protein. Immunization studies show this induces potent neutralizing antibody responses in mice, rabbits cynomolgus macaques. vaccine-induced immunity protected macaques against high dose...
The SARS-CoV-2 pandemic is continuing to disrupt personal lives, global healthcare systems and economies. Hence, there an urgent need for a vaccine that prevents viral infection, transmission disease. Here, we present two-component protein-based nanoparticle displays multiple copies of the spike protein. Immunization studies show this induces potent neutralizing antibody responses in mice, rabbits cynomolgus macaques. vaccine-induced immunity protected macaques against high dose challenge,...
A vaccine that can achieve protective immunity prior to sexual debut is critical prevent the estimated 410,000 new HIV infections occur yearly in adolescents. As children living with make broadly neutralizing antibody (bnAb) responses plasma at a faster rate than adults, early childhood an opportune window for implementation of multi-dose immunization strategy elicit adolescence. Therefore, goal our study was assess ability B cell lineage-designed envelope SOSIP induce bnAbs life. Infant...
Broadly neutralizing antibodies (bNAbs) have remarkable breadth and potency against most HIV-1 subtypes are able to prevent infection in animal models. However, bNAbs extremely difficult induce by vaccination. Defining the developmental pathways towards neutralization can assist design of strategies elicit protective bNAb responses Here, envelope glycoproteins (Env)-specific IgG + B cells were isolated at various time points post from an infected elite neutralizer obtain monoclonal (mAbs)....