Understanding the requirements for enhanced onset to immunity using light-based immune modulation for pulsatile presentation of foreign responses
Abstract
Vaccines that require multiple administrations are a problem in public and military health. Giving multiple shots limits the completion rate for many vaccines. For deployed or domestic service members, it means they often do not get their booster shots before encountering a bio-weapon of mass destruction. Research into single-dose vaccines will help solve this problem by enabling one shot vaccinations - improving health rates at home and saving lives on the battlefield. To develop a single-dose vaccine, a better understanding of how the immune system works throughout the life of a vaccination is needed. To gain this understanding, we will develop new technologies that can activate the immune system over the period of 1 yr. These technologies will activate the immune system in a controlled fashion without activating it, by accident, at earlier time points. Our goal in this project is to develop this technology and to test how activating the immune system in different ways will help improve single-dose vaccines. We propose a new technology that allow us to control how the immune system responds to a vaccination. Normally, when infected, two signals are sent to the immune system. The first, is a very fast warning to directly combat and destroy the disease - inflammation. The second is a slow signal to prime the rest of the immune system should the infection return - antigen presentation. These two signals are coupled and cannot yet be fully separated. Vaccines take advantage of this second signal to prime the immune response before an infection occurs. However, because they must rely on the first signal, many vaccines waste much of their potential as the first signal to combat and destroy is fast and cannot be made persistent over time without complications. Our proposal will separate these two signals and include them in a time-release formulation to help us control where and when inflammation and antigen presentation occur. By separating inflammation from antigen presentation, we can make vaccines that are more effective over a longer period while causing less of the problems that require multiple boosts. We propose to develop a new technology that acts as a potent, antigen presenting vaccine, but can rest inside the body – cloaked - for up to 1 yr without activating the immune system. By controlling the moment that it activates, we can create multiple boosting events in a single dose without leading to the issues associated with implantation, injection or with multiple boosting events. Using this technology, we can control when an immune response gets turned on and how much of the response is focused towards inflammation and how much to antigen presentation. This basic knowledge will help improve single-dose vaccines with our target being improvement of a single dose vaccine against a potential bio-weapon - Q-fever.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jul 16, 2019
- Source ID
- HDTRA11810052
Entities
People
- Aaron Esserkahn
Organizations
- Defense Threat Reduction Agency
- University of Chicago