User:Samira S. Daswani/Notebook/WF orange
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Sixing Zhao and Samira Daswani
In vivo Antigen Delivery for HIV vaccine
According to the WHO, the HIV epidemic continues to kill ~2 million deaths per year. The rapid mutation of the virus, and its ability to kill cells of the immune system plays a key role in containing the infection. Research to develop a prophylatic vaccine have made some headway. Significant advancements have been made in bio-inspired, bioengineered and biomimetic drug delivery carriers. For our project, we would like to investigate intracellular delivery of protein or nucleic acid antigens in light of a HIV vaccine.
The immune system has evolved to respond to antigens that are in micro- or nano-particulate form. We want to design a biodegradable polymer micro- or nano-particle as a potential vaccine delivery carrier. The ability to control the release rate of components and the inherent potency of degradable particles for vaccine delivery, particularly PLGA, can be used to improve the immune response. Additionally, particles can co-deliver immunostimulatory molecules on the same particle. We want to combine this concept of antigen surface-display with a strategy for creating degradable particles whose surfaces could mimic microbial pathogens. This pathogen-mimetic surface structure would enhance immune responses to delivered antigens.
1. Bershteyn A, Hanson MC, Crespo MP, Moon JJ, Li AV, Suh H, and Irvine DJ, “Robust IgG responses to nanograms of antigen using a biomimetic lipid-coated particle vaccine” Elsevier 2012; 157 (3): 354-265
The authors of this paper studied subunit vaccine formulations that increased the potency of the vaccines to promote less doses of certain vaccines. Here, they used poly(lactide-co-glycolide) micro or nano particles in PEGylated phospholipid bilayers with protein antigens attached to the lipid surface and lipophilic adjuvants imbedded in the bilayer coating. This structure enhances the potency of the micro or nano particles on humoral immune responses. These particles were found to elicit high antigen-specific IgG titers at low doses. Thus, lipid-enveloped biodegradable micro and nano particles are a great platform for high potent low dose vaccine delivery.
2. De Temmerman M-L, Rejman J, Demeester J, Irvine DJ, Gander B, and De Smedt SC, “Particulate vaccines: on the quest for optimal delivery and immune response,” Drug Discov Today 2011; 16(13-14): 569-82
Subunit vaccines presents an antigen to the immune system without introducing viral particles. This can be done by isolating a specific protein from a virus and administering the protein alone. However, protein are easily denatured in the body and are not easily targeted to the virus. This review covers the many attempts to overcome this problem by using micro and nano delivery systems that carry the antigen. The review addresses the past work done on antigen-delivery vehicles to obtain safe and efficient vaccines.