A Milk Protein-Hitchhiking Strategy for the Oral Delivery of Amphiphilic Vaccines
Abstract
Service members and civilian populations are potentially exposed to many emerging infectious diseases that are life-threatening. These include, but are not limited to, Zika virus (ZIKV), dengue, HIV, norovirus, hepatitis, and Middle East Respiratory Syndrome. However, many of these diseases remain among the leading causes of illness and death in the battlefield and account for substantial spending on the related consequences of infection even after Soldiers come back from the service. Many infectious diseases, however, can be prevented through vaccination. Developing a convenient and cost-effective vaccine delivery technology that can be deployed to Service members and civilians remains highly desirable. Oral vaccination is a very powerful and effective approach for vaccination because it can not only induce a broad immunity through the blood and lymphatics, but also help patrol a very thin lining in the respiratory, digestive, and reproductive systems for potential virus invasion. The latter is particularly important as many pathogens invade the body via sexual or respiratory transmission. However, the stomach presents a major barrier to successful delivery of protein-based vaccines to the intestines, in which immune cells would otherwise receive alarm signals. The stomach is highly acidic and also contains proteins that recognize vaccines as food sources to chop up. To address this challenge, we draw inspiration from two seemingly irrelevant disciplines -- dairy science and bioconjugation chemistry -- to develop a “plug and play” type of approach for oral delivery of vaccines. Our strategy is to repurpose a milk protein, alpha-lactalbumin, as a vehicle, which is known to be resistant to degradation by stomach. Since this protein naturally associates with many bioactive lipids such as vitamin D, we propose to explore a range of lipid molecules derived from a common supplement (e.g., vitamin D) and vegetable oil (e.g., oleic acid). As a proof-of-principle study, we will link lipid molecules to a short strand of amino acids that serves as the “ID” for ZIKV, and a short DNA sequence that serve as the “danger” signal to reinforce the vaccination. We envision that co-administering these two components with alpha-lactalbumin will help them from being cleared by the stomach, and therefore a stronger signal will be sent to immune cells lying underneath the intestines. While this work focuses on ZIKV, this strategy can work in theory for many other infectious pathogens in a “plug and play” fashion. Importantly, this formulation can in principle maintain long shelf lives in a form of dry powder and be administered along with water, which enables easy deployment to Service members and civilian populations to prevent infectious diseases.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910041
Entities
People
- Jiahe Li
Organizations
- Northeastern University
- United States Army