Background Cytotoxic T lymphocyte (CTL) vaccine carriers are known to enhance the efficacy of vaccines, but a search for more effective carriers is warranted. Elastin-like polypeptides (ELPs) have been examined for many medical applications but not as CTL vaccine carriers. Purpose We aimed to create immune tolerant ELPs using a new polypeptide engineering practice and create CTL vaccine carriers using the ELPs. Results Four sets of novel ELPs, termed immune-tolerant elastin-like polypeptide (iTEP) were generated according to the principles dictating humoral immunogenicity of polypeptides and phase transition property of ELPs. The iTEPs were non-immunogenic in mice. Their phase transition feature was confirmed through a turbidity assay. An iTEP nanoparticle (NP) was assembled from an amphiphilic iTEP copolymer plus a CTL peptide vaccine, SIINFEKL. The NP facilitated the presentation of the vaccine by dendritic cells and enhanced vaccine-induced CTL responses. Discussion A new ELP design and development practice was established. The non-canonical motif and the immune tolerant nature of the iTEPs broaden our insights about ELPs. ELPs, for the first time, were successfully used as carriers for CTL vaccines. Conclusion It is feasible to concurrently engineer both immune-tolerant and functional peptide materials. ELPs are a promising type of CTL vaccine carriers.

In vivo 19F NMR at 4.7 T has shown that the biphasic elimination of the vapor anesthetic isoflurane from rat brain is ca 15% slower in old (23-24 months) animals compared with young (5-6 months) animals. The fast kinetic component has a t1/2 of ca 7-9 min and the slow event, 100-115 min. Gas chromatographic measurement of arterial blood elimination displays age attenuation to the same extent, although a monophasic kinetic process (6-7 min). The slow wash-out from brain is thought to involve elimination from intracranial fatty tissue as postulated by others in rabbit brain. Longitudinal relaxation time measurements show monoexponential recovery and essentially identical values for young (1.09 + 0.11 s) and old (1.04 +/- 0.09 s) animals. For dipalmitoylphosphatidylcholine vesicles the monoexponential recovery also suggests rapidly exchanging averaged homogeneous lipid environments for the anesthetic, but the longer T1s (2.75 +/- 0.25 s) imply less restricted mobility compared with brain. Single T2 values were obtained in vivo, indicating either a single compartment or rapid exchange between multiple environments. These measurements were inconsistent, undoubtedly as a result of B1 inhomogeneity. The age-attenuated elimination kinetics for isoflurane are consistent with poorer cardiopulmonary function, whereas the T1 data suggest similar environments for the anesthetic in young and old brain tissue.

No abstract

No abstract

No abstract