Polylactide-co-glycolide (PLG) microparticles modify the immune response to DNA vaccination

Vaccine
Rebecca HelsonPeter J M Openshaw

Abstract

Priming with the major surface glycoprotein G of respiratory syncytial virus (RSV) expressed by recombinant vaccinia leads to strong Th2 responses and lung eosinophilia during viral challenge. We now show that DNA vaccination in BALB/c mice with plasmids encoding G attenuated RSV replication but also enhanced disease with lung eosinophilia and increased IL-4/5 production. However, formulating the DNA with PLG microparticles reduced the severity of disease during RSV challenge without significantly lessening protection against viral replication. PLG formulation greatly reduced lung eosinophilia and prevented the induction of IL-4 and IL-5 during challenge, accompanied by a less marked CD4+ T cell response and a restoration of the CD8+ T cell recruitment seen during infection of non-vaccinated animals. After RSV challenge, lung eosinophilia was enhanced and prolonged in mice vaccinated with DNA encoding a secreted form of G; this effect was virtually prevented by PLG formulation. Therefore, PLG microparticulate formulation modifies the pattern of immune responses induced by DNA vaccination boosts CD8+ T cell priming and attenuates Th2 responses. We speculate that PLG microparticles affect antigen uptake and processing, thereby in...Continue Reading

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Citations

Jan 10, 2012·Cold Spring Harbor Perspectives in Medicine·Richard A Koup, Daniel C Douek
Aug 20, 2010·Pharmaceutical Research·Yogita KrishnamachariAliasger K Salem
Oct 14, 2010·Cell Biochemistry and Function·Maria Augusta RoosAntonio Ponzetto
Jun 28, 2016·Scientific Reports·Jiwon HanSukho Park
Oct 1, 2010·Critical Reviews in Biotechnology·Clarence M OngkudonMichael K Danquah

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