Cooperative Center for Human Immunology

The Rockefeller University received a renewed round of funding from the National Institute of Allergy and Infectious Diseases (NIAID) for a Cooperative Center on Human Immunology (CCHI) at The Rockefeller University (U19AI111825).

Significant progress in basic immunology research over the last three decades has resulted in numerous medical advances and dissected the general mechanisms by which the human immune system responds to foreign antigens. However, a much more substantial understanding of the coordinated molecular mechanisms involved in eliciting immunity will be required, as each viral pathogen poses unique challenges to the immune system and the elicited immune responses are characterized by substantial heterogeneity that impacts disease susceptibility and pathogenesis. Indeed, it is expected that B-cell responses against diverse viral pathogens are uniquely evolved during infection to shape the functional activity of IgG antibodies. Studies from viral infectious diseases have shown that antiviral IgG antibodies have the capacity to mediate a wide spectrum of opposing functions: (i) protective functions, including neutralization, viral opsonization, and clearance of infected cells and (ii) pathogenic activities, which enhance viral infectivity, disease susceptibility and severity; a phenomenon termed as antibody-mediated enhancement (ADE) of disease. ADE mechanisms have been previously suggested to account for susceptibility to dengue disease, as epidemiological data support that prior flavivirus infection is the major risk factor for dengue disease, implicating the presence of cross-reactive, non-neutralizing IgG antibodies to this process. Understanding the heterogeneity of IgG responses elicited upon infection or vaccination with diverse viral antigens is therefore critical for characterizing the immunological mechanisms that drive human immunity and determine the protective vs. pathogenic activity of IgG antibodies.

Our Center will feature three Projects directed by Drs. Ravetch (Project 1: Fc domain effector activity in dengue disease), Nussenzweig and Rice (Project 2: Understanding B cell memory in response to diverse virus infections), and Wang (Project 3: Immunity to dengue viruses), supported by a scientific core (Core A: Transgenic mouse core) and the administrative core (Core B). Through a series of collaborative studies between the three Projects, our Center aims to study human antiviral immune responses during infection and vaccination and characterize the immune mechanisms that regulate the function of IgG antibodies in humans. More specifically, we aim to characterize the heterogeneity of IgG responses elicited upon vaccination or infection with diverse viral pathogens, including Zika and dengue. Additionally, we will dissect the ADE mechanisms by which IgG antibodies mediate disease-enhancing activities and contribute to dengue disease susceptibility and pathogenesis. These studies will provide novel insights into the mechanisms that drive protective immunity and modulate antibody function, having a broader impact on the development of vaccination strategies against infectious pathogens.

The purpose of this website is to allow for interested parties to access information on the investigators, CCHI, and each research project, as well as advertise upcoming CCHI-sponsored events around campus, and provide further information related to publications and past presentations from members of the CCHI and its External Scientific Advisory Group.

 

The Rockefeller University received a renewed round of funding from the National Institute of Allergy and Infectious Diseases (NIAID) for a Cooperative Center on Human Immunology (CCHI) at The Rockefe