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RISS 인기검색어
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- 저자 : Ratto-Kim, Silvia (검색결과 2 건)
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O'Connell, Robert J.,Excler, Jean-Louis,Polonis, Victoria R.,Ratto-Kim, Silvia,Cox, Josephine,Jagodzinski, Linda L.,Liu, Michelle,Wieczorek, Lindsay,McNeil, John G.,El-Habib, Raphaelle,Michael, Nelson Oxford University Press 2016 The Journal of Infectious Diseases Vol.213 No.12
<P>Background. Prime-boost regimens comprising ALVAC-HIV (prime) and human immunodeficiency virus type 1 (HIV) Env (boost) induce HIV-specific neutralizing antibody and cell-mediated immune responses, but the impact of boost schedule and adjuvant requires further definition. Methods. A phase 1 trial was conducted. In part A (open label), 19 volunteers received oligomeric glycoprotein 160 from HIV strains MN and LAI-2 (ogp160 MN/LAI-2) with dose escalation (25, 50, 100 mu g) and either polyphosphazene (pP) or alum adjuvant. In part B, 72 volunteers received either placebo (n=12) or recombinant canarypox virus expressing HIV antigens (ALVAC-HIV [vCP205]) with different doses and schedules of ogp160 MN/LAI-2 in pP or alum (n = 60). Results. The vaccines were safe and well tolerated, with no vaccine-related serious adverse events. Anti-gp70 V1V2 antibody responses were detected in 17 of 19 part A volunteers (89%) and 10%-100% of part B volunteers. Use of a peripheral blood mononuclear cell-based assay revealed that US-1 primary isolate neutralization was induced in 2 of 19 recipients of ogp160 protein alone (10.5%) and 5 of 49 prime-boost volunteers (10.2%). Among ogp160 recipients, those who received pP were more likely than those who received alum to have serum that neutralized tier 2 viruses (12% vs 0%; P = .015). Conclusions. Administration of ogp160 with pP induces primary isolate tier 2 neutralizing antibody responses in a small percentage of volunteers, demonstrating proof of concept and underscoring the importance of further optimization of prime-boost strategies for HIV infection prevention.</P>
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Liu, Fengliang,Fan, Xiuzhen,Auclair, Sarah,Ferguson, Monique,Sun, Jiaren,Soong, Lynn,Hou, Wei,Redfield, Robert R.,Birx, Deborah L.,Ratto-Kim, Silvia,Robb, Merlin L.,Kim, Jerome H.,Michael, Nelson L.,H Public Library of Science 2016 PLoS pathogens Vol.12 No.6
<▼1><P>Loss of immune control over opportunistic infections can occur at different stages of HIV-1 (HIV) disease, among which mucosal candidiasis caused by the fungal pathogen <I>Candida albicans (C</I>. <I>albicans)</I> is one of the early and common manifestations in HIV-infected human subjects. The underlying immunological basis is not well defined. We have previously shown that compared to cytomegalovirus (CMV)-specific CD4 cells, <I>C</I>. <I>albicans-specific</I> CD4 T cells are highly permissive to HIV <I>in vitro</I>. Here, based on an antiretroviral treatment (ART) naïve HIV infection cohort (RV21), we investigated longitudinally the impact of HIV on <I>C</I>. <I>albicans</I>- and CMV-specific CD4 T-cell immunity <I>in vivo</I>. We found a sequential dysfunction and preferential depletion for <I>C</I>. <I>albicans-</I>specific CD4 T cell response during progressive HIV infection. Compared to Th1 (IFN-γ, MIP-1β) functional subsets, the Th17 functional subsets (IL-17, IL-22) of <I>C</I>. <I>albicans-</I>specific CD4 T cells were more permissive to HIV <I>in vitro</I> and impaired earlier in HIV-infected subjects. Infection history analysis showed that <I>C</I>. <I>albicans-</I>specific CD4 T cells were more susceptible to HIV <I>in vivo</I>, harboring modestly but significantly higher levels of HIV DNA, than CMV-specific CD4 T cells. Longitudinal analysis of HIV-infected individuals with ongoing CD4 depletion demonstrated that <I>C</I>. <I>albicans-</I>specific CD4 T-cell response was preferentially and progressively depleted. Taken together, these data suggest a potential mechanism for earlier loss of immune control over mucosal candidiasis in HIV-infected patients and provide new insights into pathogen-specific immune failure in AIDS pathogenesis.</P></▼1><▼2><P><B>Author Summary</B></P><P>HIV infection is closely associated with enhanced host susceptibility to various opportunistic infections (OIs), among which mucosal candidiasis caused by the fungal pathogen <I>Candida albicans</I> (<I>C</I>. <I>albicans</I>) is an early and common manifestation. Even in the era of effective ART, mucosal candidiasis is still a clinically relevant presentation in HIV-infected patients. The underlying mechanisms are not well defined. CD4-mediated immunity is the major host defense mechanism against <I>C</I>. <I>albicans</I>. We here investigated a group of ART naïve, HIV-infected human subjects and examined longitudinally the impact of HIV on <I>C</I>. <I>albicans</I>-specific CD4 T-cell immunity as compared to CD4 T-cell immunity specific for CMV, another opportunistic pathogen that usually does not cause active disease in early HIV infection. We found that <I>C</I>. <I>albicans</I>-specific CD4 T cells were more susceptible to HIV <I>in vivo</I> and were preferentially depleted in progressive HIV-infected individuals as compared to CMV-specific CD4 T cells. Of importance, we also found that in these HIV-infected subjects <I>C</I>. <I>albicans</I>-specific CD4 T cell response manifested a sequential dysfunction with earlier impairment of Th17, but not Th1, functions. Our study suggests an immunological basis that helps explain the earlier and more common onsets of mucosal candidiasis in progressive HIV-infected patients.</P></▼2>
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