摘要:
The hepatitis B virus (HBV) capsid is made up of a single species of protein called the core antigen (HBcAg) which self-assembles into particles. The particles are highly immunogenic and are able to present heterologous epitopes to the immune system when the epitopes are inserted into a surface-exposed region of the particles called the "e1 loop". The structural building blocks of the particles are tightly associated dimers of HBcAg in which the adjacent e1 loops are closely juxtaposed. It is proposed that sequences inserted into the e1 loop are conformationally restrained in the assembled particles when presented in monomeric core protein. The invention seeks to solve this problem by covalently linking core proteins as tandem copies (e.g., as dimers) so that insertions can be made independently in each copy. This is particularly useful for insertion of large sequences into the e1 loop because it allows such sequences to be inserted into just one copy of the core protein per tandem repeat, thereby reducing potential conformational clashes in assembly. Alternatively, a different sequence may be inserted into each e1 loop of a tandem repeat, thus increasing the flexibility of HBcAg particles as an epitope delivery system.
摘要:
It is intended to provide an HBV precore protein capable of forming particles and a means of assaying the same. A novel HBV precore protein forming HBV virus-like particles is identified. Thus, this novel HBV precore protein is provided. It is also intended to provide core-like particles and virus-like particles formed by this HBV precore protein. These virus-like particles are usable in vaccines and remedies. Moreover, it is intended to provide a method of assaying the HBV precore protein and a method of assaying an anti-HBV precore protein antibody.
摘要:
The invention is related to polynucleotide-based cytomegalovirus vaccines. In particular, the invention is plasmids operably encoding HCMV antigens, in which the naturally-occurring coding regions for the HCMV antigens have been modified for improved translation in human or other mammalian cells through codon optimization. HCMV antigens which are useful in the invention include, but are not limited to pp65, glycoprotein B (gB), IEI, and fragments, variants or derivatives of either of these antigens. In certain embodiments, sequences have been deleted, e.g., the Arg435-Lys438 putative kinase in pp65 and the membrane anchor and endocellular domains in gB. The invention is further directed to methods to induce an immune response to HCMV in a mammal, for example, a human, comprising delivering a plasmid encoding a codon-optimized HCMV antigen as described above. The invention is also directed to pharmaceutical compositions comprising plasmids encoding a codon-optimized HCMV antigen as described above, and further comprising adjuvants, excipients, or immune modulators.
摘要:
A method for designing antigenic peptide libraries accounts for naturally occurring and potential variability in a group of protein sequences from a variable pathogen. The peptide libraries can elicit an immune response against a range of pathogen variants.
摘要:
The invention relates to an isolated nucleic acid sequence, obtainable from the genome of the HXHV virus, in particular, the nucleic acid sequence comprising the sequence SEQ ID NO: 4 or the complementary sequence to SEQ ID NO: 4, polypeptides coded by said nucleic acid sequences and uses thereof.
摘要:
The invention provides a method for designing protein immunogen, which comprises (a) modifying the amino acid sequence of the immunogen, and (b) determining whether the T-helper (Th) cell response to the modified immunogen is of the Th1 type or the Th2 type. The method is useful in identifying immunogens for use in immunotherapy of diseases. For example, chronic hepatitis is believed to be associated with a Th2-dominated response which fails to clear the virus, and switching the Th response to a Th1 response by administration of an immunogen that induces a Th1 response may help in clearing the virus.
摘要:
A protein is provided comprising hepatitis B core antigen (HBcAg) wherein one or more of the four arginine repeats has been deleted, said protein comprising the C-terminal cysteine of HBcAg. The deleted region may be replaced by an epitope from a protein other than HBcAg, in which case the HBcAg acts as a carrier to present the epitope to the immune system. The chimeric protein is useful in prophylactic and therapeutic vaccination of a host, for example against hepatitis B virus.
摘要:
A chimeric, carboxy-terminal truncated hepatitis B virus nucleocapsid protein (HBc) is disclosed that is engineered for both enhanced stability of self-assembled particles and the display of an immunogenic epitope. The display of the immunogenic epitope is displayed in the immunogenic loop of HBc, whereas the enhanced stability of self-assembled particles is obtained by the presence of at least one heterologous cysteine residue near the carboxy-terminus of the chimer molecule. Methods of making and using the chimers are also disclosed.
摘要:
An isolated HCV peptide of 15 residues or less, comprising a sequence selected from the group consisting of:
KLVALGINAV (SEQ ID NO:175) SLMAFTAAV (SEQ ID NO:176) CINGVCWTV (SEQ ID NO:177) TISGVLWQV (SEQ ID NO:178) SISGVLWQV (SEQ ID NO:179) SLMAFTASV(SEQ ID NO:180) GLRDCTMLV (SEQ ID NO:181) KLVALGVNAV(SEQ ID NO:182) KLSGLGLNAV (SEQ ID NO:183) LLCPAGHAV (SEQ ID NO:186) LLFNILGWV (SEQ ID NO:187) and
any of the above sequences modified by one or two conservative substitutions.