John Garner

PLA-PEG-Maleimide from PolySciTech used in development of long-lasting vaccines against infections

Blog Post created by John Garner on May 14, 2019

The human immune system can be visualized as an angry guard dog on a long chain. The dog has enough power and bite to destroy just about anything within its area but, in order to be effective, it must be trained carefully as to who is and is not allowed within its sector (i.e. “self” versus “non-self” designations). In this metaphor, vaccine technology would be equivalent to showing the guard dog a picture of a known thief and instructing it to bite said thief on sight. Of course, humans cannot ‘speak’ to the immune system, so unraveling the biochemical language by which the immune system can be ‘trained’ to attack deadly pathogens is critical to preventing epidemics. Recently, researchers at DILIsym Services Inc., Mylan Pharmaceuticals Inc., University of Nebraska, Eppley Institute for Research in Cancer and Allied Diseases, San Diego State University, and Creighton University used mal-PEG-PLA (AI050) from PolySciTech (www.polyscitech.com) to create modified nanoparticles which were decorated with an immunogenic-peptide on the outside to act as an adjuvant in vaccine technology. This research holds promise for the development of more effective vaccines against a wide range of diseases. Read more: Tallapaka, Shailendra B., Bala VK Karuturi, Pravin Yeapuri, Stephen M. Curran, Yogesh A. Sonawane, Joy A. Phillips, D. David Smith, Sam D. Sanderson, and Joseph A. Vetro. "Surface conjugation of EP67 to biodegradable nanoparticles increases the generation of long-lived mucosal and systemic memory T-cells by encapsulated protein vaccine after respiratory immunization and subsequent T-cell-mediated protection against respiratory infection." International Journal of Pharmaceutics (2019). https://www.sciencedirect.com/science/article/pii/S0378517319303667

“Abstract: Encapsulation of protein vaccines in biodegradable nanoparticles (NP) increases T-cell expansion after mucosal immunization but requires incorporating a suitable immunostimulant to increase long-lived memory T-cells. EP67 is a clinically viable, host-derived peptide agonist of the C5a receptor that selectively activates antigen presenting cells over neutrophils. We previously found that encapsulating EP67-conjugated CTL peptide vaccines in NP increases long-lived memory subsets of CTL after respiratory immunization. Thus, we hypothesized that alternatively conjugating EP67 to the NP surface can increase long-lived mucosal and systemic memory T-cells generated by encapsulated protein vaccines. We found that respiratory immunization of naïve female C57BL/6 mice with LPS-free ovalbumin (OVA) encapsulated in PLGA 50:50 NP (∼380 nm diameter) surface-conjugated with ∼0.1 wt% EP67 through 2 kDa PEG linkers (i.) increased T-cell expansion and long-lived memory subsets of OVA323-339-specific CD4+ and OVA257-264-specific CD8a+ T-cells in the lungs (CD44HI/CD127/KLRG1) and spleen (CD44HI/CD127/KLRG1/CD62L) and (ii.) decreased peak CFU of OVA-expressing L. monocytogenes (LM-OVA) in the lungs, liver, and spleen after respiratory challenge vs. encapsulation in unmodified NP. Thus, conjugating EP67 to the NP surface is one approach to increase the generation of long-lived mucosal and systemic memory T-cells by encapsulated protein vaccines after respiratory immunization. Keywords: mucosal vaccine vaccine delivery nanoparticle targeted vaccines dendritic cell targeting CD88 host-derived immunostimulant complement-derived immunostimulant”

 

Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register to attend at www.bpcrconference.com

Outcomes