Talk Title: Modulation of humoral immunity during immunization through control of vaccine kinetics

 

Darrell J. Irvine1-5;

1Koch Institute, MIT; 2 Scripps CHAVD, 3 Biological Eng and Materials Science & Eng, MIT; 4 Ragon Institute of MGH, MIT, and Harvard; 5 HHMI

Abstract: Following infection, even “acute” viral and bacterial infections are often accompanied by prolonged antigen and/or inflammatory cue exposure, which can extend weeks after infectious pathogen is cleared. This is in contrast the relatively short duration of antigen/inflammation that accompanies many subunit vaccines. Motivated by these differences, we have been interested in whether the timing of antigen/inflammatory cues is important in the immune response to vaccines, and particularly for humoral immune responses. We recently showed in both small and large animal models that prolonged exposure to vaccine antigen and adjuvants significantly enhances germinal center (GC) responses, increases output antibody titers, and increases the number of distinct B cell clones able to enter GC responses. These enhanced responses correlated with enhanced antigen capture in follicles during “extended dosing” immunizations. However, clinically-relevant methods to control the duration of antigen delivery to lymph nodes in subunit vaccines are lacking. We conjugated antigens derived from the HIV envelope with a phosphoserine (pSer) peptide that binds tightly to the most common clinical adjuvant, aluminum hydroxide (Alhydrogel, or alum). Tight binding to alum converted alum itself into an “extended dosing”, nanoparticle delivery vehicle, where alum particles carrying antigen slowly arrived at lymph nodes over several weeks. This change in kinetics and the form of antigen exposure to B cells triggered 30-fold increases in germinal center responses, increased serum antibody titers and plasma cell development, and enhanced neutralizing antibody responses relative to the unmodified antigens. Thus, engineering immunogen binding to alum may provide a simple and broadly-applicable strategy to enhance the efficacy of subunit vaccines. Currently, we are exploring this same technology as a means to localize immunomodulatory drugs in tumors for cancer immunotherapy.

Biography

Prof. Irvine holds a Bachelor's Degree in Engineering Physics from University of Pittsburgh. After completing his PhD at MIT in Polymer Science, he continued his postdoctoral research in Immunology at Stanford University. Darrell Irvine joined MIT in 2002 as Assistant Professor of Biomedical Engineering, Department of Material Science and Engineering and the then Biological Engineering Division.

Research

Engineering approaches grounded in immunology hold the key to the discovery and development of novel treatments for cancer, infectious disease, and autoimmunity. To this end, the overarching goal of the Irvine laboratory is to engineer immunity through a fusion of immunology with biotechnology and materials chemistry, employing a materials science-centric approach to create new therapies based on the controlled modulation of the immune system. Our work toward this goal divides into three complimentary themes, all focused on adapting engineering principles to enhance the ability of the immune system to prevent and treat human disease:

1. Smart materials and nanotechnology for enhanced vaccines against infectious disease and cancer. We develop synthetic materials as adjuvants and delivery systems that shape the immune response elicited by vaccination, and study the underlying biological mechanisms governing this response.

2. Nanomaterials-enabled immunotherapy. Here we are exploring strategies to promote, amplify, and maintain anti-tumor immune responses by controlling where and when cells of the immune system receive stimulatory cues, and seeking to overcome the immunosuppressive milieu developed in solid tumors.

3. New tools for manipulating and monitoring the immune system. We develop biomaterials-based approaches to monitor and manipulate immune cells, to increase our fundamental understanding of the immune system and invent new methods for monitoring immunity in humans.

Institutional Profile: Darrell J. Irvine, PhD | MIT Department of Biological Engineering

 

A 'Tea with the Speaker' will follow this seminar, where Pathway 2/PGR staff and Undergraduate students are warmly encouraged to join in an informal discussion with the speaker following their talk. 

Professor Darrell Irvine