Immunological responses after immunisation of mice with microparticles containing antigen and single stranded RNA (polyuridylic acid).
Certain toll-like receptor (TLR) agonists, e.g. CpG DNA, can be used as potent vaccine 'adjuvants'. It is known that some sequences of single stranded (ss) RNA stimulate proinflammatory and antiviral responses following interaction with TLR 7 and 8. We have encapsulated ovalbumin (OVA) in the presence and absence of polyuridylic acid (poly-U) inside polylactide microparticles. In comparison to microparticles containing only OVA, bulk cultures of bone marrow-derived plasmacytoid and myeloid dendritic cells produced more (P<0.05) IL-12 and interferon (IFN)-alpha when stimulated with microparticles containing OVA and poly-U. Subcutaneous injection of comicroencapsulated OVA and poly-U resulted in statistically elevated levels of serum anti-OVA IgG1 (P<0.05 versus naïve mice). Conversely, anti-OVA IgG1 levels in C57 BL6 mice immunised with OVA loaded microparticles (without RNA) were statistically indifferent to naïve animals. Furthermore, injection of coencapsulated OVA and poly-U resulted in (P<0.05) greater numbers of OVA specific IFN-gamma secreting T-cells as compared with mice injected with OVA loaded microparticles. A similar trend was seen in mice immunised with OVA loaded microparticles decorated with CpG or solutions of admixed OVA and CpG (P<0.05). These data demonstrate, for the first time, that appropriately formulated ssRNA can act as a potent adjuvant and modulator of adaptive immunological responses.
Westwood
Angie
A
Building 7A, DSTL, Porton Down, Salisbury SP4 0JQ, UK.
Elvin
Stephen J
SJ
Healey
Gareth D
GD
Williamson
E Diane
ED
Eyles
Jim E
JE
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000906:Antibodies / Q000097:blood; D003713:Dendritic Cells / Q000276:immunology; D004339:Drug Compounding; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D016898:Interferon-alpha / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008863:Microspheres; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000276:immunology; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology*; D011072:Poly U / Q000008:administration & dosage / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D051193:Toll-Like Receptors
D000276:Adjuvants, Immunologic; D000906:Antibodies; C408982:CPG-oligonucleotide; D007074:Immunoglobulin G; D016898:Interferon-alpha; D009838:Oligodeoxyribonucleotides; D051193:Toll-Like Receptors; D018664:Interleukin-12; D011072:Poly U; D010047:Ovalbumin