Todd Allen

..However, current HIV vaccine designs are largely based on viral sequence alignments only, not incorporating experimental data on T cell function and specificity...

..By themselves, these strong CTL responses failed to control SIVmac239 replication...

..These data suggest that targeting these and other conserved viral regions may be the key to developing an effective HIV-1 vaccine...

..Alternative approaches to long-term control of viral replication and disease progression are clearly needed...

..CONCLUSION: These data demonstrate that host genetic factors can influence the clinical manifestations of acute HIV-1 infection and provide a functional link between HLA-B57 and viral immune control...

..These data suggest that subdominant responses can contribute to in vivo viral control and that high HLA allele frequencies may drive the elimination of subdominant yet effective epitopes from circulating viral populations...

..Differential selection by CTL may therefore be a paradigm of immunodeficiency virus infection...

..Together, these data indicate that viral escape from CD8+ T cell responses occurs during human HCV infection and that acute immune selection pressure is of sufficient magnitude to influence HCV evolution...

..The stereotypic nature of acquired mutations provides support for biochemical constraints limiting HIV-1 evolution and for the impact of CD8 escape mutations on viral fitness...

..These data show the influence of HLA allele subtypes on TCR selection and indicate that extensive TCR diversity is not a prerequisite to prevention of allowable viral mutations...

..In most of the Mamu-A*01-positive macaques tested, CTL responses against epitopes bound by Mamu-A*01 dominated the CD8(+) cellular immune response...

..Moreover, reversion of these mutations in the absence of the original immune pressure reveals the potential plasticity of immunologically selected evolutionary changes...

..However, despite these immunological changes, no differences in viremia or in the CD4+ T cell count were found 6 months after HAART was stopped, when treated subjects were compared with untreated subjects...

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..These data also support a role for cellular immune pressures in driving the selection of new recombinant forms of HIV...

..Despite the induction of Tat-specific CTL, there was no significant reduction in either peak or viral set point compared to that of controls...

..Our data show that full maturation of virus-specific CD8+ T cells is possible in the context of HIV-1-infection, and suggest that such maturation might be important in viral control...

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..Our results provide a conceptual framework that unifies diverse empirical observations, and have implications for vaccination strategies...

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..The lack of cross-protective immunity for closely related HIV-1 strains, despite persistent recognition of multiple CD8 epitopes, has important implications for public health and vaccine development...

..These data demonstrate that immunization with hybrid HBcAg-epitope DNA vaccines is an effective strategy to increase the magnitude and breadth of HIV-specific CTL responses...

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..Our results suggest that acute viral escape from CTLs is a hallmark of SIV infection and that CTLs with high functional avidity can rapidly select for escape variants...

..These results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection...

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..Of the common MHC class I alleles, animals that expressed Mamu-A*01 exhibited the best control of viral replication...

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..Later diversification of responses to other proteins during prolonged antigen exposure provides evidence of the initial preferential immunogenicity of Nef epitopes compared to similarly conserved regions within other viral proteins...

..Taken together, these findings indicate that the developing immune system of children may exhibit greater plasticity in responding to a continually evolving chronic viral infection...

..Herein, we illustrate the long-term stability of stereotypic escape mutations in the immunodominant HLA-B27-restricted epitope KK10 in p24/Gag following transmission when accompanied by a specific compensatory mutation...

..These data suggest a dual mechanism for durable control of HIV replication, consisting of viral fitness loss resulting from CTL escape mutations together with strong CD8 T-cell immune responses to the arising variant epitopes...

..We aimed to determine the correlations between these alleles and natural outcomes of HCV and determine associated key T-cell responses...

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..To evaluate the recognition of computationally designed, centralized HIV-1 antigens derived from clade B, C and group M sequences by individuals infected with HIV-1-M clades B and C...

..Dramatic differences in escape and reversion rates across codons, genes, and HLA restrictions are observed, highlighting the complexity of viral adaptation to the host immune response...

..Our data indicate that most CD8 T-cell responses in chronic HCV infection do not target the circulating virus and that the appearance of HCV-specific CD127(+) T cells is driven by viral variation...

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..Our results suggest that an analysis of PD-1 expression alone is not sufficient to predict infection outcome or to determine T-cell functionality in HCV infection...

..The persistence of drug-resistance mutations argues for baseline resistance genotyping at the time therapy is initiated to accurately predict the efficacy of treatment...

..Toggled peptides therefore afford a cost-effective and significantly more complete view of the host immune response to HIV and are directly applicable to other variable pathogens...

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..These results reveal considerable concordance of adaptive cellular and humoral immune responses and HIV evolution in the same genetic environment, suggesting constraints on mutational pathways to HIV immune escape...

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..They also demonstrate that CD8 T-cell responses to the variable HIV-1 proteins are more common than previously reported...

..Here we examined the effect of a lymphotropic virus, HIV-1, on the ability of coinfected patients to maintain spontaneous control of HCV infection...

..This comprehensive characterization of CD4(+) T cell epitopes in resolved HCV infection provides important information to facilitate studies of immunopathogenesis and HCV vaccine design and evaluation...

..Abrogated recognition of variant CD4(+) T cell epitopes presents a potential obstacle to vaccine development...

..These results indicate that the spontaneous control of HIV replication is not attributable to shared viral genetic defects or shared viral polymorphisms...

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..These results suggest that HIV-1-specific cytotoxicity of CD8(+) T cells is preferentially mediated by a subset of CD8(+) T cells secreting both interferon-gamma and TNF-alpha...

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..These parallel in vivo and in vitro data suggest that HLA-B57 confers its advantage primarily by driving and maintaining a fitness-attenuating mutation in p24-Gag...

..To illustrate the importance of escape analysis, we show that rapid emergence of escape variants postchallenge contributed to the failure of a DNA prime/MVA boost vaccine regimen encoding SIV Tat...

..These data suggest that high-avidity HIV-1-specific CD8+ T-cell clones are recruited during early infection but are subsequently lost in the presence of persistent high-level viral replication...

..The data support an important role of the presented epitope in mediating relative control of HIV replication and help to better define immune correlates of controlled HIV infection...

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..These observations have important implications for vaccine approaches that may need to induce high-avidity responses in vivo...

..These data provide the first functional evidence that variation at the KIR locus influences the effectiveness of NK cell activity in the containment of viral replication...

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..Our results predict that the diversity of TCR clonotypes responding to pathogens like HCV will be very similar in both species and will facilitate a molecular dissection of the immune response in chimpanzee models of human diseases...

..Thus, immunization with MVA/SHIV89.6 alone or with a protein boost stimulated both arms of the immune system and resulted in significant control of viremia and delayed progression to disease after challenge with SHIV-89.6P...

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..Analyses in a second cohort in the United States confirm these findings and point towards a dominant role of Gag-specific immunity in effective control of HIV infection, providing important guidance for HIV vaccine development...

..Immunizing before infection or with multi-epitopes enhanced these effects. These results demonstrate that DNA immunization during antiretroviral therapy may be an effective strategy to treat HIV infection...

..Herein we review the published reports of HIV-1 superinfection and highlight studies providing additional insight into the potential for HIV-1 superinfections to affect the global epidemic...

..Our findings illustrate the flexibility of a heterogeneous HIV-1-specific CD8+ TCR repertoire in subjects with partial control of viremia...

..These data suggest that broad CD8(+) T-cell responses alone may be insufficient to contain HCV replication, and also that early therapy is effective independent of such responses...

..In conclusion, this FACS-based method provides a sensitive approach to measure the replication capacity of HIV-1 and may prove useful in studies examining the impact of viral fitness on disease progression...

..Thus, our results suggest that factors other than mutational escape contribute to the failure of intrahepatic virus-specific CD8+ T-cells...

..The proposed project, therefore, will use whole viral genome sequencing along with cellular assays to examine these issues. ..

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..The proposed project, therefore, will use whole viral genome sequencing along with cellular assays to examine these issues. ..

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..The proposed project, therefore, will use whole viral genome sequencing along with cellular assays to examine these issues. ..

..The potency of these responses will be tested in a new humanized mouse model to identify immune responses critical to the design of an effective HIV vaccine. ..