Cellular mechanism for immunogenicity of PEGylated 'stealth' liposomes (IRC3P.466)
| Autor: | Akiko Watanabe, Derek Cain, Melissa Hanson, Mikyung Kim, Ellis Reinherz, Darrell Irvine, Garnett Kelsoe |
|---|---|
| Rok vydání: | 2014 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 192:59.9-59.9 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.192.supp.59.9 |
| Popis: | Liposomes have been used as a vehicle to deliver pharmaceutical agents and as a carrier of vaccine antigens for malaria, cancer and HIV. The potency of a liposome-based vaccination is affected by the lipid formulation and inclusion of adjuvants, in addition to the immunogenicity of target antigens. While liposomal vaccines elicit robust humoral responses against target antigens, recent studies have shown that lipid components, such as monophosphoryl lipid A (MPLA), or liposome adducts, such as polyethylene glycol (PEG), are also capable of being targets of induced antibody. To understand the cellular interactions and molecular pathways responsible for the anti-liposome responses, we immunized mice with PEGylated “stealth” liposomes containing lipid-arrayed membrane-proximal external region (MPER) of HIV-1, and followed the kinetics of the humoral responses against liposome components as well as MPER. Immunized mice mounted robust IgM and IgG against PEG and, to a lesser extent, MPLA. PEG IgG was dependent on CD154, yet the requirement for T cells was less stringent. Moreover, PEG IgG was generated independent of MHCII, CD1d, and TCRδ, suggesting a novel form of T-cell help. Anti-MPER IgG, in contrast, was dependent on CD154, MHCII, and LAT. These results suggest that anti-liposome IgG responses are induced by atypical T-B cognate interaction, which is independent of CD4, NKT and γδ T cells and are distinct from MPER IgG responses, which require classical T-B collaboration. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|