Methods and compositions for inducing an immune response using conserved element constructs
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example 1
Illustration of Enhanced Immune Responses Obtained with CE Construct Prime Followed by CE and Full-Length Polypeptides as Boost
[0257]This example evaluated prime-boost combination vaccines to increase breadth of immunity. In addition to the CE prime-full length molecule boost, it was found that using a boost involving co-delivery of CE and full-length molecule resulted in significantly further improved breadth of the responses. This boost further elicited higher levels of cytotoxic T cells focusing the immune responses to the highly conserved epitopes.
[0258]Method: this study was performed using a simian immunodeficiency virus (SIV) derived conserved element pDNA vaccine that was designed from the SIV p27gag capsid protein by analogy to an HIV CE vaccine. The SIV p27gag is the proteolytic processing product derived from the full length SIV p57gag protein. Seven highly conserved elements were identified within the p27gag capsid protein by (i) analogy to HIV CE sequences and (ii) sequ...
example 2
Env DNA Vaccination Induces Cross-Clade Specific Cellular Immune Responses in Mice
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Conserved Element DNA Vaccines
[0270]A set of conserved elements (CE) was identified in the HIV Env protein (FIG. 9). This example describes the identification of 12 conserved elements in HIV Env of 11, 14, 21, 15, 23, 21, 13, 12, 14, 43, 20, and 13 AA in length (FIG. 10). Each CE segment is separated by linkers 3 amino acids in length, composed of alanine and some of which also contain a valine, glutamic acid, lysine, aspartic acid, phenylalanine or glycine, designed to facilitate processing of the protein. Expression-optimized synthetic Env-CE1 and Env-CE2 genes were inserted into an eukaryotic expression vector pCMVkan between the human CMV promoter and bovine growth hormone poly A signal. pCMVkan is optimized for optimal growth in bacteria (kanR) and expression of the insert in mammalian cells.
[0271]Regions for inclusion / exclusion from the vaccine were selected based on whether immune respons...
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