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Comparison of Antibody Responses Induced by RV144, VAX003, and VAX004 Vaccination Regimens
Karnasuta, Chitraporn,Akapirat, Siriwat,Madnote, Sirinan,Savadsuk, Hathairat,Puangkaew, Jiraporn,Rittiroongrad, Surawach,Rerks-Ngarm, Supachai,Nitayaphan, Sorachai,Pitisuttithum, Punnee,Kaewkungwal, J MARY ANN LIEBERT INC PUBL 2017 AIDS RESEARCH AND HUMAN RETROVIRUSES Vol.33 No.5
<P><B>Abstract</B></P><P>The RV144 prime-boost regimen demonstrated efficacy against HIV acquisition while VAX003 and VAX004 did not. Although these trials differed by risk groups, immunization regimens, and immunogens, antibody responses may have contributed to the differences observed in vaccine efficacy. We assessed HIV-specific IgG, both total and subclass, and IgA binding to HIV envelope (Env): gp120 proteins and Cyclic V2 (CycV2) and CycV3 peptides and gp70 V1 V2 scaffolds in these 3 HIV vaccine trials. After two protein immunizations, IgG responses to 92TH023 gp120 (contained in ALVAC-HIV vaccine) were significantly higher in RV144 but responses to other Env were higher in the VAX trials lacking ALVAC-HIV. IgG responses declined significantly between vaccinations. All trials induced antibodies to gp70 V1 V2 but VAX004 responses to 92TH023 gp70 V1 V2 were weak. All CycV2 responses were undetectable in VAX004 while 92TH023 gp70 V1 V2 was detected in both RV144 and VAX003 but MN CycV2 was detected only in VAX003. Multiple protein vaccinations in VAX trials did not improve magnitude or durability of V1 V2 and CycV2 antibodies. Herpes simplex virus glycoprotein D (gD) peptide at the N terminus of AIDSVAX<SUP>®</SUP> B/E and B/B gp120 proteins induced antibodies in all trials, although significantly higher in VAX trials. gD peptide induced IgA, IgG1, IgG2, and IgG3 but not IgG4. Multiple protein vaccinations decreased IgG3 and increased IgG4 changing subclass contribution to total IgG. Although confounded by different modes of HIV transmission, higher Env-specific IgA and IgG4 binding antibodies induced in the VAX trials compared to RV144 raises the hypothesis that these differences may have contributed to different vaccine efficacy results.</P>
Park, Sae-Gwang,Jung, Young-Joo,Lee, Young-Yi,Yang, Cheul-Min,Kim, Ik-Jung,Chung, Jun-Ho,Kim, Ik-Sang,Lee, Youn-Jae,Park, Sung-Jae,Lee, Jeong-Nyeo,Seo, Su-Kil,Park, Yong-Hong,Choi, In-Hak MARY ANN LIEBERT INC PUBL 2006 VIRAL IMMUNOLOGY Vol.19 No.1
<P>CDR3 of the heavy-chain variable region of immunoglobulin is a region in which somatic mutation occurs heavily after secondary antibody response, resulting in an affinity maturation of antibodies in vivo. The aim of this study was to improve the affinity of a human single-chain variable fragment (scFv) specific for pre-S1 of hepatitis B virus (HBV) by introducing random mutagenesis in CDR3 variable region of heavy chain (V(H)) of the parental scFv clone 1E4. By using a BIAcore for panning and screening, we have selected three clones (A9, B2, and B9) with lower highest affinity (K(D)) than 1E4. Affinities of selected clones ranged from 1.7 x 10(7) mol/L to 6.3 x 10(8) mol/L, which were increased by factors of 1.4 to 4.0, respectively, compared to the parental clone. Binding inhibition assay using flow cytometry and polymerase chain reaction revealed that B2 (6.4 x 10(8) mol/L) had a higher neutralizing activity against pre-S1 or HBV virion binding to liver cell line. This anti-pre-S1 scFv can be considered as a potential therapeutic tool for a passive immunotherapy for HBV infection.</P>
CCR2b-64I Allelic Polymorphisms in Advanced HIV-Infected Koreans Accelerate Disease Progression
Choi, Byeong-Sun,Choi, Jang-Hoon,Kim, Sung Soon,Kee, Mee-Kyung,Lee, Joo-Shil MARY ANN LIEBERT INC PUBL 2007 AIDS RESEARCH AND HUMAN RETROVIRUSES Vol.23 No.6
<P>Genetic polymorphisms of chemokine genes and chemokine-receptor genes in HIV-infected patients have been associated with delayed progression of this disease. The allelic frequencies of these genetic variants also differ between ethnic groups. To investigate the effects of the SDF1 and CCR2b genotypes on disease progression, survival of 200 HIV-infected persons for whom at least four subsequent immunologic data items had been collected was analyzed. A genotyping assay of SDF1 and CCR2b genes was carried out using polymerase chain reaction-restriction fragment length polymorphism analyses. HIV-infected persons heterozygous for the SDF1-3'A or CCR2b-64I alleles were included in the survival analysis, but homozygotes were excluded because of a very small sample number. Neither the CCR2b-+/64I allele nor the SDF1-+/3'A allele, separately or in combination, had a significant impact on survival during the asymptomatic period of HIV infection. However, CCR2b-+/64I alleles were associated with accelerated disease progression during the advanced period of HIV infection. The survival time of HIV-infected people with CCR2b-+/64I and SDF1-+/+ genotypes was significantly shorter than those of the other groups (p < 0.01), but this effect was not apparent in persons with CCR2b-+/64I alleles and SDF1-+/3'A genotypes. These results suggest that the effect of CCR2b-64I polymorphisms on disease progression may differ according to the stage of HIV infection and interactions with other gene variants.</P>
HIV-1 Genetic Diversity Among Incident Infections in Mbeya, Tanzania
Billings, Erik,Sanders-Buell, Eric,Bose, Meera,Kijak, Gustavo H.,Bradfield, Andrea,Crossler, Jacqueline,Arroyo, Miguel A.,Maboko, Leonard,Hoffmann, Oliver,Geis, Steffen,Birx, Deborah L.,Kim, Jerome H. MARY ANN LIEBERT INC PUBL 2017 AIDS RESEARCH AND HUMAN RETROVIRUSES Vol.33 No.4
<P><B>Abstract</B></P><P>In preparation for vaccine trials, HIV-1 genetic diversity was surveyed between 2002 and 2006 through the Cohort Development study in the form of a retrospective and prospective observational study in and around the town of Mbeya in Tanzania's Southwest Highlands. This study describes the molecular epidemiology of HIV-1 strains obtained from 97 out of 106 incident HIV-1 infections identified in three subpopulations of participants (one rural, two urban) from the Mbeya area. Near full-genome or half-genome sequencing showed a subtype distribution of 40% C, 17% A1, 1% D, and 42% inter-subtype recombinants. Compared to viral subtyping results previously obtained from the retrospective phase of this study, the overall proportion of incident viral strains did not change greatly during the study course, suggesting maturity of the epidemic. A comparison to a current Phase I-II vaccine being tested in Africa shows ∼17% amino acid sequence difference between the gp120 of the vaccine and subtype C incident strains. Phylogenetic and recombinant breakpoint analysis of the incident strains revealed the emergence of CRF41_CD and many unique recombinants, as well as the presence of six local transmission networks most of which were confined to the rural subpopulation. In the context of vaccine cohort selection, these results suggest distinct infection transmission dynamics within these three geographically close subpopulations. The diversity and genetic sequences of the HIV-1 strains obtained during this study will greatly contribute to the planning, immunogen selection, and analysis of vaccine-induced immune responses observed during HIV-1 vaccine trials in Tanzania and neighboring countries.</P>
Karasavvas, Nicos,Karnasuta, Chitraporn,Savadsuk, Hathairat,Madnote, Sirinan,Inthawong, Dutsadee,Chantakulkij, Somsak,Rittiroongrad, Surawach,Nitayaphan, Sorachai,Pitisuttithum, Punnee,Thongcharoen, P MARY ANN LIEBERT INC PUBL 2015 AIDS RESEARCH AND HUMAN RETROVIRUSES Vol.31 No.11
<P><B>Abstract</B></P><P>RV144 correlates of risk analysis showed that IgG antibodies to gp70V1V2 scaffolds inversely correlated with risk of HIV acquisition. We investigated IgG antibody responses in RV135 and RV132, two ALVAC-HIV prime-boost vaccine trials conducted in Thailand prior to RV144. Both trials used ALVAC-HIV (vCP1521) at 0, 1, 3, and 6 months and HIV-1 gp120MNgD and gp120A244gD in alum (RV135) or gp120SF2 and gp120CM235 in MF59 (RV132) at 3 and 6 months. We assessed ELISA binding antibodies to the envelope proteins (Env) 92TH023, A244gD and MNgD, cyclicV2, and gp70V1V2 CaseA2 (subtype B) and 92TH023 (subtype CRF01_AE), and Env-specific IgG1 and IgG3. Antibody responses to gp120 A244gD, MNgD, and gp70V1V2 92TH023 scaffold were significantly higher in RV135 than in RV132. Antibodies to gp70V1V2 CaseA2 were detected only in RV135 vaccine recipients and IgG1 and IgG3 antibody responses to A244gD were significantly higher in RV135. IgG binding to gp70V1V2 CaseA2 and CRF01_AE scaffolds was higher with the AIDSVAX<SUP>®</SUP>B/E boost but both trials showed similar rates of antibody decline post-vaccination. MF59 did not result in higher IgG antibody responses compared to alum with the antigens tested. However, notable differences in the structure of the recombinant proteins and dosage used for immunizations may have contributed to the magnitude and specificity of IgG induced by the two trials.</P>
Late Presentation into Care of HIV Disease and Its Associated Factors in Asia: Results of TAHOD
Jeong, Su Jin,Italiano, Claire,Chaiwarith, Romanee,Ng, Oon Tek,Vanar, Sasheela,Jiamsakul, Awachana,Saphonn, Vonthanak,Nguyen, Kinh Van,Kiertiburanakul, Sasisopin,Lee, Man Po,Merati, Tuti Parwati,Pham, MARY ANN LIEBERT INC PUBL 2016 AIDS RESEARCH AND HUMAN RETROVIRUSES Vol.32 No.3
Eo, Jungwoo,Cha, Hee-Jae,Imai, Hiroo,Hirai, Hirohisa,Kim, Heui-Soo MARY ANN LIEBERT INC PUBL 2014 AIDS RESEARCH AND HUMAN RETROVIRUSES Vol. No.
<P>Endogenous retroviruses (ERVs), which are footprints of ancient germline infections, were inserted into the genome during the early stages of primate evolution. Human endogenous retroviruses (HERVs) occupy approximately 8% of the human genome. Although most ERV genes are defective, with large deletions, stop codons, and frameshifts in their open reading frames (ORFs), some full-length sequences containing long ORFs are expressed in several tissues and cancers. Several envelope glycoproteins that are encoded by env genes have retained some characteristics of their ancestral infectious viruses. These glycoproteins play essential physiological roles in the organs in which they are expressed. Previous studies have demonstrated the expression of ERV env at the mRNA level in cells and tissues rather than at the protein level, which is more difficult to detect. However, it is not known whether Env is functionally conserved in primates. To understand the possible role of Env in primates, we examined the expression of the env genes of four ERVs (ERV-R, -K, -W, and -FRD) at the protein as well as mRNA levels in various tissues of the rhesus monkey. The ERV env gene products were observed at moderate to high levels in each tissue that was examined and showed tissue-specific expression patterns. Our data suggest a biologically important role for retroviral proteins in healthy tissues of the rhesus monkey.</P>
Jeong, Su Jin,Kim, Min Hyung,Song, Je Eun,Ahn, Jin Young,Kim, Sun Bean,Ann, Hea Won,Kim, Jae Kyung,Choi, Heun,Ku, Nam Su,Han, Sang Hoon,Kim, June Myung,Smith, Davey M.,Kim, Hyon-Suk,Choi, Jun Yong MARY ANN LIEBERT INC PUBL 2014 AIDS Research and Human Retroviruses Vol. No.
<P>Less costly but still accurate methods for monitoring HIV treatment response are needed. We prospectively evaluated if a qualitative polymerase chain reaction (PCR) amplification assay for virologic monitoring could maintain accuracy while reducing costs in Seoul, South Korea. We conducted the first prospective study comparing a qualitative PCR amplification of HIV-1 reverse transcriptase (RT) versus a commercial real time PCR assay (i.e., viral load) for virologic monitoring of 150 patients receiving antiretroviral therapy (ART) between November 2011 and August 2012 at an urban hospital in Seoul, South Korea. A total of 215 blood plasma samples from 150 patients receiving ART for more than 6 months were evaluated. Using the individual viral load assay, 12 of 215 (5.6%) plasma samples had more than 500 HIV RNA copies/ml. The qualitative PCR amplification assay detected individual samples with 500 HIV RNA copies/ml with 100% sensitivity. The specificities of the qualitative PCR amplification of the HIV-1 RT assay were 94.1%, 93.6%, and 93.2% compared to the real time PCR at 500, 1,000, and 5,000 threshold of HIV RNA copies/ml, respectively, and $24,940 USD would have been saved for 150 patients during 10 months. The qualitative PCR amplification of the HIV-1 RT assay might be a useful approach to effectively monitor patients receiving ART and save resources.</P>