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Comprehensive Sieve Analysis of Breakthrough HIV-1 Sequences in the RV144 Vaccine Efficacy Trial
Edlefsen P.T. - ไม่ระบุหน่วยงาน
ชื่อเรื่อง (EN): Comprehensive Sieve Analysis of Breakthrough HIV-1 Sequences in the RV144 Vaccine Efficacy Trial
ผู้แต่ง / หัวหน้าโครงการ (EN): Edlefsen P.T.
บทคัดย่อ (EN): The RV144 clinical trial showed the partial efficacy of a vaccine regimen with an estimated vaccine efficacy (VE) of 31% for protecting low-risk Thai volunteers against acquisition of HIV-1. The impact of vaccine-induced immune responses can be investigated through sieve analysis of HIV-1 breakthrough infections (infected vaccine and placebo recipients). A V1/V2-targeted comparison of the genomes of HIV-1 breakthrough viruses identified two V2 amino acid sites that differed between the vaccine and placebo groups. Here we extended the V1/V2 analysis to the entire HIV-1 genome using an array of methods based on individual sites, k-mers and genes/proteins. We identified 56 amino acid sites or “signatures” and 119 k-mers that differed between the vaccine and placebo groups. Of those, 19 sites and 38 k-mers were located in the regions comprising the RV144 vaccine (Env-gp120, Gag, and Pro). The nine signature sites in Env-gp120 were significantly enriched for known antibody-associated sites (p = 0.0021). In particular, site 317 in the third variable loop (V3) overlapped with a hotspot of antibody recognition, and sites 369 and 424 were linked to CD4 binding site neutralization. The identified signature sites significantly covaried with other sites across the genome (mean = 32.1) more than did non-signature sites (mean = 0.9) (p < 0.0001), suggesting functional and/or structural relevance of the signature sites. Since signature sites were not preferentially restricted to the vaccine immunogens and because most of the associations were insignificant following correction for multiple testing, we predict that few of the genetic differences are strongly linked to the RV144 vaccine-induced immune pressure. In addition to presenting results of the first complete-genome analysis of the breakthrough infections in the RV144 trial, this work describes a set of statistical methods and tools applicable to analysis of breakthrough infection genomes in general vaccine efficacy trials for diverse pathogens. © 2015 Ferdinandy et al.
บทคัดย่อ: ไม่พบข้อมูลจากหน่วยงานต้นทาง
ภาษา (EN): en
เอกสารแนบ (EN): https://www.scopus.com/inward/record.uri?eid=2-s2.0-84995610492&doi=10.1371%2fjournal.pcbi.1003973&partnerID=40&md5=fa1a0f0c5ee5b60568eae0a4e3134bb0
เผยแพร่โดย (EN): มหาวิทยาลัยมหิดล
คำสำคัญ (EN): Sequence Analysis, Protein
เจ้าของลิขสิทธิ์ (EN): มหาวิทยาลัยมหิดล
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Edlefsen P.T.. "Comprehensive Sieve Analysis of Breakthrough HIV-1 Sequences in the RV144 Vaccine Efficacy Trial". ไม่ระบุหน่วยงาน. ม.ป.ป.

Edlefsen P.T.. "Comprehensive Sieve Analysis of Breakthrough HIV-1 Sequences in the RV144 Vaccine Efficacy Trial". ไม่ระบุหน่วยงาน. ม.ป.ป.. Print.



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Comprehensive Sieve Analysis of Breakthrough HIV-1 Sequences in the RV144 Vaccine Efficacy Trial
Edlefsen P.T.
มหาวิทยาลัยมหิดล
ไม่ระบุวันที่เผยแพร่
Accuracy of clinical diagnosis of dengue episodes in the RV144 HIV vaccine efficacy trial in Thailand CD8 and CD4 epitope predictions in RV144: No strong evidence of a T-cell driven sieve effect in HIV-1 Breakthrough sequences from trial participants Characterization of HIV-1 gp120 antibody specificities induced in anogenital secretions of RV144 vaccine recipients after late boost immunizations Hepatitis B and C co-infection in HIV patients from the TREAT Asia HIV observational database: Analysis of risk factors and survival Modulation of vaccine-induced CD4 T cell functional profiles by changes in components of HIV vaccine regimens in humans Drinking fermented milk containing Lactobacillus paracasei 431 (IMULUS™) improves immune response against H1N1 and cross-reactive H3N2 viruses after influenza vaccination: A pilot randomized triple-bl Monoclonal antibodies, derived from humans vaccinated with the RV144 HIV vaccine containing the HVEM binding domain of herpes simplex virus (HSV) glycoprotein D, neutralize HSV infection, mediate anti Prevalence of HIV infection, access to HIV care, and response to antiretroviral therapy among partners of HIV-infected individuals in Thailand National Survey of Pretreatment HIV-Drug Resistance in Thai HIV-1-Infected Adults Efficacy and safety of topical Trikatu preparation in, relieving mosquito bite reactions : A randomized controlled trial
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