Natalia Freund Lab for Human Antibody Responses
Department of Microbiology and Immunology, Sackler School of Medicine
Antibodies are the basis for most vaccines and they can be protective against pathogens.
The main focus of our research is to understand how antibody responses develop and what are the rules for successful protective antibody responses. To answer these key questions, we develop and apply a variety of molecular, genetic and computational immunological tools, and use different models, such as HIV-1, Mtb, SARS Coronavirus 2 (SARS-CoV-2), and cancer.
Our ultimate goal is to exploit our knowledge of the human antibody responses for the development of new diagnostic tools, immune-treatments and for the discovery of new vaccine targets.
Isolation of broadly neutralizing antibodies against SARS CoV-2
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological cause of coronavirus-induced disease 19 (COVID-19) that emerged in late 2019 causing a worldwide epidemic.
SARS-CoV-2 belongs toathe family Coronaviridae together with SARS-CoV that emerged in 2002 causing approximately 8000 infections with the lethality of 10%. Both viruses are the result of a zoonotic transfer from an animal reservoir that caused a life-threatening respiratory illness in humans. Along with other accumulating evidence, our working hypothesis that SARS-CoV-2 convalescent individuals have protective anti-SARS-CoV-2 immunity, and particularly, antibodies.
In this study, we aim to isolate anti-SARS Co-V-2 broadly neutralizing antibodies (bNAbs) bNAbs from convalescent COVID-19 patients and to generate a panel of candidates for treatment and prevention of COVID-19.
Antibody responses to Mycobacterium tuberculosis
In collaboration with: Dr. Danielle Bendayan, Lung division, Shmuel Harofe Hospital, Dr. Oren Zimchoni, Kaplan Hospital
Mycobacterium Tuberculosis (MTb) is the cause of Tuberculosis disease and is the top infectious agent worldwide according to the WHO. In the last century, MTb was successfully controlled with highly efficient antibiotic treatment. However, recently the number of antibiotic-resistant MTb cases increased dramatically.
Our goal is to characterize and B cell response to Mtb and isolate anti-mob inhibiting antibodies that in the future can be translated into new antibody-based therapeutics, diagnostics, and vaccine candidates for MTb. For that, we isolate and characterize the antibodies that are naturally produced in response to MTb in infected individuals.
Neutralizing anti-HIV-1 antibodies
Human immunodeficiency virus 1 (HIV-1) is the etiologic cause of infectious AIDS disease. According to the WHO, in 2016 35 million people were infected with the virus and 1.2 million people died from AIDS. The current antiretroviral treatment is efficient in keeping low levels of viremia, however, the virus is not completely eliminated by this treatment and some levels persist through latency and low-level replication. It is important therefore to investigate alternative strategies to eliminate HIV-1.
A small fraction of HIV-1 infected individuals produces neutralizing antibodies that show potent neutralizing activity against a broad range of different HIV-1 isolates. Our goal is to characterize new broadly anti-HIV-1 antibodies from infected patients with the aim of identifying new antibody-base therapeutics and new potential vaccine targets
Discovery of anti-tumor antibodies
In collaboration with Dr. Einav Gal-Yam, Sheba Cancer Center
Monoclonal antibodies are widely used for the treatment of specific types of tumors.
Our goal is to understand the natural antibody immune response against tumors in breast and lung cancer patients by isolating naturally produced antibodies against tumor-associated antigens (TAA). We use single-cell antibody sequencing methods for the discovery of new anti-tumor antibodies that can potentially be used in the clinic for the diagnostic and treatment of patients.
Vaccination under stress
In collaboration with: Shamgar Ben-Eliyahu, PhD, Gordon Faculty of Social Sciences.
Stress plays a central role in physiological regulation, including modulation of the immune system. However, the effects of stress on antibody-mediated immune response following vaccination are still unknown. In this project we investigate the effects of stress-induced β-adrenergic receptor activation on the B cell response following vaccination at the molecular and the systemic levels. We use both in vitro boost immunization model, a mouse model as well as molecular immunology tools in order to study what antibodies are elicited during stress, and compare them to antibodies and B cells under non-stress conditions.