Abstract: We identified regions of the HIV-1 proteome with high conservation, and low variant incidence. Such highly conserved sequences have direct relevance to the development of new-generation vaccines and diagnostic applications. The immune relevance of these sequences was assessed by their correlation to previously reported human T-cell epitopes and to recently identified human HIV-1 T-cell epitopes (identified using HLA transgenic mice). We identified (a) sequences specific to HIV-1 with no shared identity to other viruses and organisms, and (b) sequences that are specific to primate lentivirus group, with multiclade HIV-1 conservation.

Abstract: Flaviviruses represent an increasing global public health issue, with no prophylactic and therapeutic formulations currently available for many of them. The combination of factors such as evolutionary change, global warming and wide range of animal hosts suggest the possible occurrence of Flavivirus strains with greater distribution and human pathogenicity. There is, thus, a need for greater understanding of viral protein sequences that function in the human immune responses. The evolutionary diversity of the reported sequences of major flaviviruses, such as dengue virus, yellow fever virus, Japanese encephalitis virus, and West Nile virus were analyzed with a combination of experimental and bioinformatics methodologies. The analysis of all reported sequences revealed that these species-specific peptide tags are highly conserved and are potential T-cell epitopes due to correspondence to known or predicted epitopes.

Abstract: Pandemic A(H1N1) continues its global spread, and vaccine production is a serious problem. Protection by current vaccines is limited by the mutational differences that rapidly accumulate in the circulating strains, especially in the virus surface proteins. New vaccine strategies are focusing at conserved regions of the viral internal proteins to produce T cell epitope-based vaccines. T cell responses have been shown to reduce morbidity and promote recovery in mouse models of influenza challenge. We previously reported 54 highly conserved sequences of NP, M1 and the polymerases of all human H1N1, H3N2, H1N2, and H5N1, and avian subtypes over the past 30 years. Sixty-three T cell epitopes elicited responses in HLA transgenic mice (A2, A24, B7, DR2, DR3 and DR4). These epitopes were compared to the 2007-2009 human H1N1 sequences to identify conserved and variant residues.

Abstract: The inventors have discovered a targeting signal that will direct proteins to the endosomal/lysosomal compartment, and they have demonstrated that chimeric proteins containing a luminal antigenic domain and a cytoplasmic endosomal/lysosomal targeting signal will effectively target antigens to that compartment, where the antigenic domain is processed and peptides from it are presented on the cell surface in association with major histocompatibility (MHC) class II molecules. Chimeric DNA encoding the antigen of interest, linked to an endosomal/lysosomal targeting sequence, inserted in an immunization vector, can introduce the chimeric genes into cells, where the recombinant antigens are expressed and targeted to the endosomal/lysosomal compartment. As a result, the antigens associate more efficiently with MHC class II molecules, providing enhanced in vivo stimulation of CD4.sup.+ T cells specific for the recombinant antigen.