Wellesley, MA, United States
Wellesley, MA, United States

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Liao Q.,Nankai University | Strong A.J.,Vaccine Technologies Inc. | Liu Y.,U.S. Center for Disease Control and Prevention | Liu Y.,Nankai University | And 7 more authors.
Vaccine | Year: 2012

The Indian rhesus macaque is the established animal model for HIV infection and vaccine research. Growing evidence suggests that the more readily available Chinese rhesus macaque may be a more relevant option. As increasing numbers of novel Chinese rhesus MHC alleles are reported, we decided to explore potential HIV vaccine epitopes in this model. We immunized forty Chinese rhesus macaques with three different HIV vaccine candidates either individually or following a prime/boost strategy. We used ELISPOT to measure immune response in vitro to HIV-1 p24C and HIV-1 gp160 peptide libraries. We identified five putative epitopes with associations to HLA-I alleles including HLA*B-2705 and HLA-B*5101 (associated with slow disease progression and low viral set point) and HLA-B*18 (associated with rapid disease progression and high viral set point). This suggests the possible use of Chinese rhesus macaques to model different disease progressions. We also explored the use of fusion proteins as stimulators in ELISPOT assays. While PBMCs from 6 monkeys responded to peptide stimulation, PBMCs from 28 monkeys responded to the anthrax lethal factor fusion proteins LFn p24C and/or LFn gp140C. Our results support the use of Chinese rhesus macaques in HIV vaccine studies. © 2011 Elsevier Ltd.


Liu Y.,Nankai University | Zhao Z.,Nankai University | Li T.,Nankai University | Liao Q.,Nankai University | And 7 more authors.
PLoS ONE | Year: 2012

Background: Host immunogenetic factors such as HLA class I polymorphism are important to HIV-1 infection risk and AIDS progression. Previous studies using high-resolution HLA class I profile data of Chinese populations appeared insufficient to provide information for HIV-1 vaccine development and clinical trial design. Here we reported HLA class I association with HIV-1 susceptibility in a Chinese Han and a Chinese Uyghur cohort. Methodology/Principal Findings: Our cohort included 327 Han and 161 Uyghur ethnic individuals. Each cohort included HIV-1 seropositive and HIV-1 seronegative subjects. Four-digit HLA class I typing was performed by sequencing-based typing and high-resolution PCR-sequence specific primer. We compared the HLA class I allele and inferred haplotype frequencies between HIV-1 seropositive and seronegative groups. A neighbor-joining tree between our cohorts and other populations was constructed based on allele frequencies of HLA-A and HLA-B loci. We identified 58 HLA-A, 75 HLA-B, and 32 HLA-Cw distinct alleles from our cohort and no novel alleles. The frequency of HLA-B*5201 and A*0301 was significantly higher in the Han HIV-1 negative group. The frequency of HLA-B*5101 was significantly higher in the Uyghur HIV-1 negative group. We observed statistically significant increases in expectation-maximization (EM) algorithm predicted haplotype frequencies of HLA-A*0201-B*5101 in the Uyghur HIV-1 negative group, and of Cw*0304-B*4001 in the Han HIV-1 negative group. The B62s supertype frequency was found to be significantly higher in the Han HIV-1 negative group than in the Han HIV-1 positive group. Conclusions: At the four-digit level, several HLA class I alleles and haplotypes were associated with lower HIV-1 susceptibility. Homogeneity of HLA class I and Bw4/Bw6 heterozygosity were not associated with HIV-1 susceptibility in our cohort. These observations contribute to the Chinese HLA database and could prove useful in the development of HIV-1 vaccine candidates. © 2012 Liu et al.


Patent
Vaccine Technologies Incorporated | Date: 2010-06-11

The present invention is directed to a method for promoting or stimulating a cell-mediated immune response to an antigen, by administering a target antigen (such as a protein) with a transport factor that contains a fragment of a bipartite protein exotoxin, but not the corresponding protective antigen. Preferred transport factors include the protective antigen binding domain of lethal factor (LFn) from B. anthracis, consisting of amino acids 1-255, preferably a fragment of at least 80 amino acids that shows at least 80% homology to LFn, and a fragment of about 105 amino acids from the carboxy portion that does not bind PA. The target antigen can include any molecule for which it would be desirable to elicit a CMI response, including viral antigens and tumor antigens.


Patent
Vaccine Technologies Incorporated | Date: 2010-06-11

Described are compositions and methods for detecting or monitoring the ability of an individual to mount a cell mediated immune response to a target antigen. Methods rely in part upon the physical association, e.g., by fusion, of a Lethal Factor (LF) polypeptide with a target antigen. The LF polypeptide moiety, including, for example, an LFn polypeptide moiety, serves as a transport factor to deliver target antigens, including full length target polypeptides, to the cytosol of an intact, living immune cell from an individual. Measurement of a cytokine response by the immune cell from the individual provides a read out of a cell cell from mediated immune response. The methods and compositions described provide diagnostic as well as prognostic information and can guide the direction of therapy.


Patent
Vaccine Technologies Incorporated | Date: 2011-06-09

The present invention generally relates to HIV compositions and methods of use. One aspect of the present invention relates to a composition comprising a pharmaceutically acceptable carrier and an antigen preparation, the antigen preparation comprising an HIV polypeptide or fragment thereof and a Bacillus anthracis lethal factor (LF) polypeptide, such as a LFn polypeptide. In some embodiments, the LF polypeptide can be fused or otherwise associated with the HIV polypeptide. Other aspect of the present invention relate to use of vaccine comprising a HIV polypeptide and a Bacillus anthracis lethal factor (LF) polypeptide in methods to enhance efficacy traditional antiretroviral therapy.

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