Tuesday, October 13, 2015

PLGA-PEG-PLGA (AK097) thermogel from PolySciTech used as adjuvant to improve vaccine efficacy

PolySciTech division of Akina, Inc. (www.polyscitech.com) provides a wide array of biodegradable block copolymers including thermogelling PLGA-PEG-PLGA block copolymers. Recently, PolySciTech’s thermogelling PolyVivo AK097, was used by researchers at Auburn University for the co-administration of a phage-based vaccine as an adjuvant. Impressively, after 4-8 weeks this co-administration of phage with thermogel yielded a statistically significant 2.5-3 fold increase in the immune response (as measured by ELISA) relative to a control delivery of the phage itself without the thermogel (Fig 6A). This indicates that the thermogel has promise as an adjuvant to boost the immune response towards vaccines and improve therapeutic efficacy of these vaccines. Read more: Samoylov, Alexandre, Anna Cochran, Bettina Schemera, Michelle Kutzler, Caitlin Donovan, Valery Petrenko, Frank Bartol, and Tatiana Samoylova. "Humoral immune responses against gonadotropin releasing hormone elicited by immunization with phage-peptide constructs obtained via phage display." Journal of Biotechnology (2015). http://www.sciencedirect.com/science/article/pii/S0168165615301498

“Abstract: Phage display is based on genetic engineering of phage coat proteins resulting in fusion peptides displayed on the surface of phage particles. The technology is widely used for generation of phages with novel characteristics for numerous applications in biomedicine and far beyond. The focus of this study was on development of phage-peptide constructs that stimulate production of antibodies against gonadotropin releasing hormone (GnRH). Phage-peptide constructs that elicit production of neutralizing GnRH antibodies can be used for anti-fertility and anti-cancer applications. Phage-GnRH constructs were generated via selection from a phage display library using several types of GnRH antibodies as selection targets. Such phage constructs were characterized for sequence similarities to GnRH peptide and frequency of their occurrence in the selection rounds. Five of the constructs with suitable characteristics were tested in mice as a single dose 5 × 1011 virions (vir) vaccine and were found to be able to stimulate production of GnRH-specific antibodies, but not to suppress testosterone (indirect indicator of GnRH antibody neutralizing properties). Next, one of the constructs was tested at a higher dose of 2 × 1012 vir per mouse in combination with a poly(lactide- co -glycolide) (PLGA)-based adjuvant. This resulted in multifold increase in GnRH antibody production and significant reduction of serum testosterone, indicating that antibodies produced in response to the phage-GnRH immunization possess neutralizing properties. To achieve optimal immune responses for desired applications, phage-GnRH constructs can be modified with respect to flanking sequences of GnRH-like peptides displayed on phage. Anticipated therapeutic effects also might be attained using optimized phage doses, a combination of several constructs in a single treatment, or application of adjuvants and advanced phage delivery systems. Keywords: filamentous phage; phage display; gonadotropin releasing hormone; GnRH antibodies; contraception; hormone-dependent reproductive cancers Abbreviations: cfu, colony forming unit; FSHR, follicle-stimulating hormone receptor; GnRH, gonadotropin releasing hormone; GnRHR, gonadotropin releasing hormone receptor; PLGA, poly(lactide- co -glycolide); PEG, polyethylene glycol; vir, virion”
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