A5038121664- SARS-CoV-2 and COVID-19 Research
- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- Immune Cell Function and Interaction
- COVID-19 Clinical Research Studies
- T-cell and B-cell Immunology
- Cancer-related Molecular Pathways
- Chronic Lymphocytic Leukemia Research
- Immunotherapy and Immune Responses
- SARS-CoV-2 detection and testing
- PI3K/AKT/mTOR signaling in cancer
- HIV/AIDS Research and Interventions
- Long-Term Effects of COVID-19
- Glycosylation and Glycoproteins Research
- Monoclonal and Polyclonal Antibodies Research
- RNA Interference and Gene Delivery
- Ubiquitin and proteasome pathways
- Psoriasis: Treatment and Pathogenesis
- Pancreatic function and diabetes
- Viral gastroenteritis research and epidemiology
- COVID-19 epidemiological studies
- vaccines and immunoinformatics approaches
- Viral Infections and Outbreaks Research
Centro de Biología Molecular Severo Ochoa
2016-2023
Universidad Autónoma de Madrid
2016-2023
Consejo Superior de Investigaciones Científicas
2016-2023
Rockefeller University
2018-2021
During the coronavirus disease-2019 (COVID-19) pandemic, severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has led to infection of millions people and claimed hundreds thousands lives. The entry virus into cells depends on receptor-binding domain (RBD) spike (S) protein SARS-CoV-2. Although there is currently no vaccine, it likely that antibodies will be essential for protection. However, little known about human antibody response SARS-CoV-21–5. Here we report 149...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected 78 million individuals and is responsible for over 1.7 deaths to date. Infection associated with the development of variable levels antibodies neutralizing activity, which can protect against infection in animal models1,2. Antibody decrease time, but, our knowledge, nature quality memory B cells that would be required produce upon reinfection not been examined. Here we report on humoral response a cohort 87 assessed at...
The emergence of SARS-CoV-2 and the ensuing explosive epidemic COVID-19 disease has generated a need for assays to rapidly conveniently measure antiviral activity SARS-CoV-2–specific antibodies. Here, we describe collection approaches based on spike-pseudotyped, single-cycle, replication-defective human immunodeficiency virus type-1 (HIV-1), vesicular stomatitis (VSV), as well replication-competent VSV/SARS-CoV-2 chimeric virus. While each surrogate exhibited subtle differences in...
Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection produces B cell responses that continue to evolve for at least a year. During time, memory cells express increasingly broad and potent antibodies are resistant mutations found in variants of concern 1 . As result, vaccination disease 2019 (COVID-19) convalescent individuals with currently available mRNA vaccines high levels plasma neutralizing activity against all tested 1,2 Here we examine evolution five months...
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected 78 million individuals and is responsible for over 1.7 deaths to date. Infection associated with development of variable levels antibodies neutralizing activity that can protect against infection in animal models. Antibody decrease time, but the nature quality memory B cells would be called upon produce re-infection not been examined. Here we report on humoral response a cohort 87 assessed at 1.3 6.2 months after...
Abstract During the COVID-19 pandemic, SARS-CoV-2 infected millions of people and claimed hundreds thousands lives. Virus entry into cells depends on receptor binding domain (RBD) spike protein (S). Although there is no vaccine, it likely that antibodies will be essential for protection. However, little known about human antibody response to 1–5 . Here we report 149 convalescent individuals. Plasmas collected an average 39 days after onset symptoms had variable half-maximal neutralizing...
SARS-CoV-2 is responsible for an ongoing pandemic that has affected millions of individuals around the globe. To gain further understanding immune response in recovered individuals, we measured T cell responses paired samples obtained average 1.3 and 6.1 mo after infection from 41 individuals. The data indicate show persistent polyfunctional antigen–specific memory could contribute to rapid recall responses. Recovered also enduring alterations relative overall numbers CD4+ CD8+ cells,...
A clinical trial was performed to evaluate 3BNC117, a potent anti–HIV-1 antibody, in infected individuals during suppressive antiretroviral therapy and subsequent analytical treatment interruption (ATI). The circulating reservoir evaluated by quantitative qualitative viral outgrowth assay (Q2VOA) at entry after 6 mo. There were no significant changes the size of before ATI, composition clones varied manner that did not correlate with 3BNC117 sensitivity. binding site amino acid variants...
HIV-1 infection requires lifelong therapy with antiretroviral drugs due to the existence of a latent reservoir transcriptionally inactive integrated proviruses. The goal cure research is eliminate or functionally silence this reservoir. To end, there are numerous ongoing studies evaluate immunological approaches, including monoclonal antibody therapies. Evaluating results these sensitive and specific measures Here, we describe relatively high-throughput combined quantitative PCR (qPCR)...
Antiretroviral therapy suppresses but does not cure HIV-1 infection due to the existence of a long-lived reservoir latently infected cells. The has an estimated half-life 44 mo and is largely composed clones CD4+ T long appears result in part from expansion contraction cell clones. However, mechanisms that govern this process are poorly understood. To determine whether might be maintained by exposure antigen, we measured responses cells small subset antigens viruses produce chronic or...
Abstract The emergence of SARS-CoV-2 and the ensuing explosive epidemic COVID19 disease has generated a need for assays to rapidly conveniently measure antiviral activity SARS-CoV-2-specific antibodies. Here, we describe collection approaches based on spike-pseudotyped, single-cycle, replication-defective human immunodeficiency virus type-1 (HIV-1) vesicular stomatitis (VSV), as well replication-competent VSV/SARS-CoV-2 chimeric virus. While each surrogate exhibited subtle differences in...
Combination antiretroviral therapy controls but does not cure HIV-1 infection because a small fraction of cells harbor latent viruses that can produce rebound viremia when is interrupted. The circulating virus reservoir has been documented by variety methods, most prominently viral outgrowth assays (VOAs) in which CD4 + T are activated to vitro, or more recently amplifying proviral near full-length (NFL) sequences from DNA. Analysis samples obtained clinical studies individuals underwent...
Successful vaccines rely on activating a functional humoral response that results from promoting proper germinal center (GC) reaction. Key in this process is the activation of follicular B cells need to acquire antigens and present them cognate CD4 T cells. Here, we report can phagocytose large antigen-coated particles, thought be exclusive specialized antigen-presenting such as macrophages dendritic We show antigen phagocytosis by BCR-driven mechanistically dependent GTPase RhoG. Using...
Modulating T cell activation is critical for treating autoimmune diseases but requires avoiding concomitant opportunistic infections. Antigen binding to the receptor (TCR) triggers recruitment of cytosolic adaptor protein Nck a proline-rich sequence in cytoplasmic tail TCR's CD3ε subunit. Through virtual screening and using combinatorial chemistry, we have generated an orally available, low-molecular weight inhibitor TCR-Nck interaction that selectively inhibits TCR-triggered with IC50...
Chronic lymphocytic leukemia (CLL) is the most frequent, and still incurable, form of in Western World. It widely accepted that cancer results from an evolutionary process shaped by acquisition driver mutations which confer selective growth advantage to cells harbor them. Clear examples are missense classic RAS genes (KRAS, HRAS NRAS) underlie development approximately 13% human cancers. Although autonomous B cell antigen receptor (BCR) signaling involved many tumor suppressor oncogenes have...
Metabolic reprogramming of germinal center B cells requires the activity R-Ras2.
Novel therapeutic and preventive strategies are needed to contain the HIV-1 epidemic. Broadly neutralizing human antibodies (bNAbs) with exceptional activity against currently being tested in prevention trials. The selection of anti-HIV-1 bNAbs for clinical development was primarily guided by their vitro Env pseudotyped viruses. Here we report on 9 now 126 Clade A, C, D PBMC-derived primary African isolates. potency breadth significantly reduced compared viruses panels. difference...
Abstract SARS-CoV-2 is responsible for an ongoing pandemic that affected millions of individuals around the globe. To gain further understanding immune response in recovered we measured T cell responses paired samples obtained average 1.3 and 6.1 months after infection from 41 individuals. The data indicate show persistent polyfunctional antigen specific memory could contribute to rapid recall responses. In addition, enduring alterations relative numbers CD4 + CD8 cells, expression...
Summary Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection produces B-cell responses that continue to evolve for at least one year. During time, memory B cells express increasingly broad and potent antibodies are resistant mutations found in variants of concern 1 . As a result, vaccination disease 2019 (COVID-19) convalescent individuals with currently available mRNA vaccines high levels plasma neutralizing activity against all tested 1, Here, we examine cell evolution 5...
Abstract Novel therapeutic and preventive strategies are needed to contain the HIV-1 epidemic. Broadly neutralizing human antibodies (bNAbs) with exceptional activity against currently being tested in prevention trials. The selection of anti-HIV-1 bNAbs for clinical development was primarily guided by their vitro Env pseudotyped viruses. Here we report on 9 now 126 Clade A, C, D PBMC-derived primary African isolates. potency breadth significantly reduced compared viruses panels. difference...
Abstract Successful vaccines rely on activating a functional humoral immune response through the generation of class-switched high affinity immunoglobulins (Igs). The germinal center (GC) reaction is crucial for this process, in which B cells are selected their search antigen and T cell help. A major hurdle to understand mechanisms cell:T cooperation has been lack an antigen-specific vitro GC system. Here we report antigen-specific, high-affinity, Igs simple 2-cell type cultures naive cells....
B-cell chronic lymphocytic leukemia (B-CLL) is the most common type of in Western world. Mutations different genes, such as TP53 and ATM, deletions specific chromosomal regions, including 11q or 17p, have been associated with a worse prognosis for disease. Recent research from our group has demonstrated that, contrary to usual cancer development process through missense mutations, B-CLL driven by overexpression small GTPase RRAS2 its wild-type form, without activating mutations. While some...