Sanofi Pasteur Vaxdesign Corporation

Virginia Commonwealth University

Vaxdesign Corporation

Donald Drake

William L Warren

Eric Mishkin

John G Tew

Russell Higbee

Heather Fahlenkamp

Guzman Sanchez-Schmitz

Anatoly Kachurin

Janice Moser

Inderpal Singh

Haifeng Song

Mohey Eldin M El Shikh

Luis Mosquera

Conan Li

Selva Sukumar

Robert Parkhill

Michael N Nguyen

David Moe

Darrell J Irvine

Vaughan Wittman

Evan Gomes

Tirumalai Kamala

Mohey Edin El Shikh

In vitro biomimetic models of the neonatal immune system are provided along with methods of using the models in pre-clinical assessment of infant immune cell-mediated and humoral responses to immunogenic stimulation, such as vaccination. The models include one comprising cord blood-derived T follicular helper cells and B cells, and one comprising cord blood-derived dendritic cells and CD4+ T cells. The models can be used, for example, to assess candidate vaccines via analysis of cellular responses to antigen and vaccine exposure.

In vitro neonatal biomimetic (nMIMIC) model and methods of using same

The present invention relates to methods for preparing an artificial immune system. The artificial immune system comprises a cell culture comprising T cells, B cells and antigen-primed dendritic cells. The artificial immune system of the present invention can be used for in vitro testing of vaccines, adjuvants, immunotherapy candidates, cosmetics, drugs, biologics and other chemicals.

Methods for testing an immune response using cultures of T cells, B cells, dendritic cells and follicular dendritic cells

Methods for testing an immune response using cultures of T cells, B cells and dendritic cells

The present invention incorporates germinal centers (GCs) into three-dimensional (3D) engineered tissue constructs (ETCs). In an embodiment, we have incorporated the GC in the design of an artificial immune system (AIS) to examine immune responses to vaccines and other compounds. Development of an in vitro GC adds functionality to an AIS, in that it enables generation of an in vitro human humoral response by human B lymphocytes that is accurate and reproducible, without using human subjects. The invention also permits evaluation of, for example, vaccines, allergens, and immunogens, and activation of human B cells specific for a given antigen, which can then be used to generate human antibodies. In an embodiment of the present invention the function of the in vitro GC is enhanced by placing FDCs and other immune cells in a 3D ETC; FDCs appear more effective over a longer time (antibody production is sustained for up to about 14 days.

Methods for assaying responses to vaccines

The present invention relates to methods of constructing an integrated artificial immune system that comprises appropriate in vitro cellular and tissue constructs or their equivalents to mimic the normal tissues that interact with vaccines in mammals. The artificial immune system can be used to test the efficacy of vaccine candidates in vitro and thus, is useful to accelerate vaccine development and testing drug and chemical interactions with the immune system.

Methods for antibody production

Methods of evaluating an immune response to an antigen

Method for determining the immunogenicity of an antigen

Co-culture lymphoid tissue equivalent (LTE) for an artificial immune system (AIS)

Artificial lymphoid tissue equivalent

In vitro germinal centers

Automatable artificial immune system (AIS)

The present invention is directed to methods for constructing and using in vivo and in vitro models of aspects of human immunity and, in particular, construction of a human immune system model for the testing of, for example, vaccines, adjuvants, immunotherapy candidates, cosmetics, drugs, biologics and other chemicals. The present invention comprises both in vivo and in vitro models of aspects of human immunity that are useful for assessing the interaction of substances with the immune system, and thus can be used to accelerate and improve the accuracy and predictability of, for example, vaccine, drug, biologic, immunotherapy, cosmetic and chemical development. The invention is also useful for the generation of human monoclonal and polyclonal antibodies.

Models for vaccine assessment

Growing community of inventors

Orlando, FL, United States of America

Donald Drake