Hosted by the School of Cellular and Molecular Medicine

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.

Zoom Webinar Link: https://bristol-ac-uk.zoom.us/j/94998759391

There will be a 'Tea with the Speaker' held virtually via Zoom after the seminar has finished, where Pathway 2, PGR and UG students are welcome to join the host for an informal chat to find out more about their background and career:

• Tea with the Speaker Zoom Link: https://bristol-ac-uk.zoom.us/j/95079209538?pwd=emc5M0svT2pZSWVtMWhzaWF3QUMyQT09 
• Meeting ID: 950 7920 9538
• Passcode: 045950

More information on the event webpage: http://www.bristol.ac.uk/cellmolmed/events/2021/professor-darrell-irvine-mit-.html.