schliessen

Filtern

 

Bibliotheken

A study of vaccine-induced immune pressure on breakthrough infections in the Phambili phase 2b HIV-1 vaccine efficacy trial

Abstract Introduction The Merck Adenovirus-5 Gag/Pol/Nef HIV-1 subtype-B vaccine evaluated in predominately subtype B epidemic regions (Step Study), while not preventing infection, exerted vaccine-induced immune pressure on HIV-1 breakthrough infections. Here we investigated if the same vaccine exer... Full description

Journal Title: Vaccine 2016, Vol.34 (47), p.5792-5801
Main Author: Hertz, T
Other Authors: Logan, M.G , Rolland, M , Magaret, C.A , Rademeyer, C , Fiore-Gartland, A , Edlefsen, P.T , DeCamp, A , Ahmed, H , Ngandu, N , Larsen, B.B , Frahm, N , Marais, J , Thebus, R , Geraghty, D , Hural, J , Corey, L , Kublin, J , Gray, G , McElrath, M.J , Mullins, J.I , Gilbert, P.B , Williamson, C
Format: Electronic Article Electronic Article
Language: English
Subjects:
Quelle: Alma/SFX Local Collection
Publisher: Netherlands: Elsevier Ltd
ID: ISSN: 0264-410X
Link: https://www.ncbi.nlm.nih.gov/pubmed/27756485
Zum Text:
SendSend as email Add to Book BagAdd to Book Bag
Staff View
recordid: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5309337
title: A study of vaccine-induced immune pressure on breakthrough infections in the Phambili phase 2b HIV-1 vaccine efficacy trial
format: Article
creator:
  • Hertz, T
  • Logan, M.G
  • Rolland, M
  • Magaret, C.A
  • Rademeyer, C
  • Fiore-Gartland, A
  • Edlefsen, P.T
  • DeCamp, A
  • Ahmed, H
  • Ngandu, N
  • Larsen, B.B
  • Frahm, N
  • Marais, J
  • Thebus, R
  • Geraghty, D
  • Hural, J
  • Corey, L
  • Kublin, J
  • Gray, G
  • McElrath, M.J
  • Mullins, J.I
  • Gilbert, P.B
  • Williamson, C
subjects:
  • Adenoviridae
  • AIDS Vaccines - administration & dosage
  • AIDS Vaccines - immunology
  • Allergy and Immunology
  • Amino acids
  • Article
  • Clinical trials
  • Cohort Studies
  • Cytotoxicity
  • Double-Blind Method
  • Epitopes - genetics
  • Epitopes - immunology
  • Female
  • gag Gene Products, Human Immunodeficiency Virus - genetics
  • gag Gene Products, Human Immunodeficiency Virus - immunology
  • Gene Frequency
  • Genomes
  • Health aspects
  • HIV (Viruses)
  • HIV Infections - prevention & control
  • HIV-1 - immunology
  • HIV-1 vaccine
  • HLA-A2 Antigen - genetics
  • HLA-A2 Antigen - immunology
  • Humans
  • HVTN-503
  • Immunity, Active
  • Infections
  • Lentivirus
  • Lymphocytes
  • Male
  • Medical research
  • Medicine, Experimental
  • Methods
  • nef Gene Products, Human Immunodeficiency Virus - genetics
  • nef Gene Products, Human Immunodeficiency Virus - immunology
  • Phambili
  • Phylogenetics
  • pol Gene Products, Human Immunodeficiency Virus - genetics
  • pol Gene Products, Human Immunodeficiency Virus - immunology
  • Proteins
  • Sample Size
  • Sieve analysis
  • Step
  • Vaccination Coverage
  • Vaccines
  • Vaccines, Synthetic - administration & dosage
  • Vaccines, Synthetic - immunology
ispartof: Vaccine, 2016, Vol.34 (47), p.5792-5801
description: Abstract Introduction The Merck Adenovirus-5 Gag/Pol/Nef HIV-1 subtype-B vaccine evaluated in predominately subtype B epidemic regions (Step Study), while not preventing infection, exerted vaccine-induced immune pressure on HIV-1 breakthrough infections. Here we investigated if the same vaccine exerted immune pressure when tested in the Phambili Phase 2b study in a subtype C epidemic. Materials and methods A sieve analysis, which compares breakthrough viruses from placebo and vaccine arms, was performed on 277 near full-length genomes generated from 23 vaccine and 20 placebo recipients. Vaccine coverage was estimated by computing the percentage of 9-mers that were exact matches to the vaccine insert. Results There was significantly greater protein distances from the vaccine immunogen sequence in Gag (p = 0.045) and Nef (p = 0.021) in viruses infecting vaccine recipients compared to placebo recipients. Twenty-seven putative sites of vaccine-induced pressure were identified (p < 0.05) in Gag (n = 10), Pol (n = 7) and Nef (n = 10), although they did not remain significant after adjustment for multiple comparisons. We found the epitope sieve effect in Step was driven by HLA A∗02:01; an allele which was found in low frequency in Phambili participants compared to Step participants. Furthermore, the coverage of the vaccine against subtype C Phambili viruses was 31%, 46% and 14% for Gag, Pol and Nef, respectively, compared to subtype B Step virus coverage of 56%, 61% and 26%, respectively. Discussion This study presents evidence of sieve effects in Gag and Nef; however could not confirm effects on specific amino acid sites. We propose that this weaker signal of vaccine immune pressure detected in the Phambili study compared to the Step study may have been influenced by differences in host genetics (HLA allele frequency) and reduced impact of vaccine-induced immune responses due to mismatch between the viral subtype in the vaccine and infecting subtypes.
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0264-410X
fulltext: fulltext
issn:
  • 0264-410X
  • 1873-2518
url: Link


@attributes
NO1
SEARCH_ENGINEprimo_central_multiple_fe
SEARCH_ENGINE_TYPEPrimo Central Search Engine
RANK2.5106418
LOCALfalse
PrimoNMBib
record
control
sourceidgale_pubme
recordidTN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5309337
sourceformatXML
sourcesystemPC
galeidA472213536
sourcerecordidA472213536
originalsourceidFETCH-LOGICAL-1688t-3862f5754277337c2c5aaaa9778ce6e6f527f89f13f6b02f3e30951d4a48d7bb3
addsrcrecordideNqNk1tv1DAQhSMEoqXwE0CWeOEliy9x4gipqKqAVqoEEhfxZjnOuOttYi92UmnFn2dWuy20LyUvuZ3zeew5UxQvGV0wyuq3q8W1sdYHWHB8XdB2QWX1qDhkqhEll0w9Lg4pr6uyYvTnQfEs5xWlVArWPi0OeNPIulLysPh9QvI09xsSHdkDSx_62UJP_DjOAcg6Qc5zAhID6RKYq2mZ4ny5JD44sJOPIeMjmZZAvizN2PnBk_XSZCC8I2fnP0p2QybgnLfGbsiUvBmeF0-cGTK82N-Piu8fP3w7PSsvPn86Pz25KFmt1FQKVXMnG1lh1UI0lltp8GqbRlmooXaSN061jglXd5Q7AYK2kvWVqVTfdJ04Ko533PXcjdBbCFMyg14nP5q00dF4ffdP8Et9Ga-1RBCuiICzHSCuIRif4I63DzDp2GteN7pnVBkFRnS8sbLnWFDbi6oTrBKKNzWi3uxrSfHXDHnSo88WhsEEiHPWTOF6nAkm_kcqq1aKWqL09T3pKs4p4KFuVaIVSrYtqhY71aUZQGP3Iu4W22F6GL2NAZzH7ydVw7EA5KJB7gw2xZwTuNt9M6q3KdQrvW-t3qZQ01ZjCtH36t8Dv3XdxA4F7-6BrZ_MNkpYkR8exL_fuQFDc-0h6Ww9BIwstsZOuo_-QcLxPYIdfMBoDlewgfz38HTmmuqv20HazhGrBVUKp-gPYskX9A
sourcetypeOpen Access Repository
isCDItrue
recordtypearticle
pqid1833938599
display
typearticle
titleA study of vaccine-induced immune pressure on breakthrough infections in the Phambili phase 2b HIV-1 vaccine efficacy trial
sourceAlma/SFX Local Collection
creatorHertz, T ; Logan, M.G ; Rolland, M ; Magaret, C.A ; Rademeyer, C ; Fiore-Gartland, A ; Edlefsen, P.T ; DeCamp, A ; Ahmed, H ; Ngandu, N ; Larsen, B.B ; Frahm, N ; Marais, J ; Thebus, R ; Geraghty, D ; Hural, J ; Corey, L ; Kublin, J ; Gray, G ; McElrath, M.J ; Mullins, J.I ; Gilbert, P.B ; Williamson, C
creatorcontribHertz, T ; Logan, M.G ; Rolland, M ; Magaret, C.A ; Rademeyer, C ; Fiore-Gartland, A ; Edlefsen, P.T ; DeCamp, A ; Ahmed, H ; Ngandu, N ; Larsen, B.B ; Frahm, N ; Marais, J ; Thebus, R ; Geraghty, D ; Hural, J ; Corey, L ; Kublin, J ; Gray, G ; McElrath, M.J ; Mullins, J.I ; Gilbert, P.B ; Williamson, C
descriptionAbstract Introduction The Merck Adenovirus-5 Gag/Pol/Nef HIV-1 subtype-B vaccine evaluated in predominately subtype B epidemic regions (Step Study), while not preventing infection, exerted vaccine-induced immune pressure on HIV-1 breakthrough infections. Here we investigated if the same vaccine exerted immune pressure when tested in the Phambili Phase 2b study in a subtype C epidemic. Materials and methods A sieve analysis, which compares breakthrough viruses from placebo and vaccine arms, was performed on 277 near full-length genomes generated from 23 vaccine and 20 placebo recipients. Vaccine coverage was estimated by computing the percentage of 9-mers that were exact matches to the vaccine insert. Results There was significantly greater protein distances from the vaccine immunogen sequence in Gag (p = 0.045) and Nef (p = 0.021) in viruses infecting vaccine recipients compared to placebo recipients. Twenty-seven putative sites of vaccine-induced pressure were identified (p < 0.05) in Gag (n = 10), Pol (n = 7) and Nef (n = 10), although they did not remain significant after adjustment for multiple comparisons. We found the epitope sieve effect in Step was driven by HLA A∗02:01; an allele which was found in low frequency in Phambili participants compared to Step participants. Furthermore, the coverage of the vaccine against subtype C Phambili viruses was 31%, 46% and 14% for Gag, Pol and Nef, respectively, compared to subtype B Step virus coverage of 56%, 61% and 26%, respectively. Discussion This study presents evidence of sieve effects in Gag and Nef; however could not confirm effects on specific amino acid sites. We propose that this weaker signal of vaccine immune pressure detected in the Phambili study compared to the Step study may have been influenced by differences in host genetics (HLA allele frequency) and reduced impact of vaccine-induced immune responses due to mismatch between the viral subtype in the vaccine and infecting subtypes.
identifier
0ISSN: 0264-410X
1EISSN: 1873-2518
2DOI: 10.1016/j.vaccine.2016.09.054
3PMID: 27756485
languageeng
publisherNetherlands: Elsevier Ltd
subjectAdenoviridae ; AIDS Vaccines - administration & dosage ; AIDS Vaccines - immunology ; Allergy and Immunology ; Amino acids ; Article ; Clinical trials ; Cohort Studies ; Cytotoxicity ; Double-Blind Method ; Epitopes - genetics ; Epitopes - immunology ; Female ; gag Gene Products, Human Immunodeficiency Virus - genetics ; gag Gene Products, Human Immunodeficiency Virus - immunology ; Gene Frequency ; Genomes ; Health aspects ; HIV (Viruses) ; HIV Infections - prevention & control ; HIV-1 - immunology ; HIV-1 vaccine ; HLA-A2 Antigen - genetics ; HLA-A2 Antigen - immunology ; Humans ; HVTN-503 ; Immunity, Active ; Infections ; Lentivirus ; Lymphocytes ; Male ; Medical research ; Medicine, Experimental ; Methods ; nef Gene Products, Human Immunodeficiency Virus - genetics ; nef Gene Products, Human Immunodeficiency Virus - immunology ; Phambili ; Phylogenetics ; pol Gene Products, Human Immunodeficiency Virus - genetics ; pol Gene Products, Human Immunodeficiency Virus - immunology ; Proteins ; Sample Size ; Sieve analysis ; Step ; Vaccination Coverage ; Vaccines ; Vaccines, Synthetic - administration & dosage ; Vaccines, Synthetic - immunology
ispartofVaccine, 2016, Vol.34 (47), p.5792-5801
rights
0Elsevier Ltd
12016 Elsevier Ltd
2Copyright © 2016 Elsevier Ltd. All rights reserved.
3COPYRIGHT 2016 Elsevier B.V.
4Copyright Elsevier Limited Nov 11, 2016
lds50peer_reviewed
oafree_for_read
citedbyFETCH-LOGICAL-1688t-3862f5754277337c2c5aaaa9778ce6e6f527f89f13f6b02f3e30951d4a48d7bb3
links
openurl$$Topenurl_article
openurlfulltext$$Topenurlfull_article
thumbnail$$Usyndetics_thumb_exl
backlink$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27756485$$D View this record in MEDLINE/PubMed
search
creatorcontrib
0Hertz, T
1Logan, M.G
2Rolland, M
3Magaret, C.A
4Rademeyer, C
5Fiore-Gartland, A
6Edlefsen, P.T
7DeCamp, A
8Ahmed, H
9Ngandu, N
10Larsen, B.B
11Frahm, N
12Marais, J
13Thebus, R
14Geraghty, D
15Hural, J
16Corey, L
17Kublin, J
18Gray, G
19McElrath, M.J
20Mullins, J.I
21Gilbert, P.B
22Williamson, C
title
0A study of vaccine-induced immune pressure on breakthrough infections in the Phambili phase 2b HIV-1 vaccine efficacy trial
1Vaccine
addtitleVaccine
descriptionAbstract Introduction The Merck Adenovirus-5 Gag/Pol/Nef HIV-1 subtype-B vaccine evaluated in predominately subtype B epidemic regions (Step Study), while not preventing infection, exerted vaccine-induced immune pressure on HIV-1 breakthrough infections. Here we investigated if the same vaccine exerted immune pressure when tested in the Phambili Phase 2b study in a subtype C epidemic. Materials and methods A sieve analysis, which compares breakthrough viruses from placebo and vaccine arms, was performed on 277 near full-length genomes generated from 23 vaccine and 20 placebo recipients. Vaccine coverage was estimated by computing the percentage of 9-mers that were exact matches to the vaccine insert. Results There was significantly greater protein distances from the vaccine immunogen sequence in Gag (p = 0.045) and Nef (p = 0.021) in viruses infecting vaccine recipients compared to placebo recipients. Twenty-seven putative sites of vaccine-induced pressure were identified (p < 0.05) in Gag (n = 10), Pol (n = 7) and Nef (n = 10), although they did not remain significant after adjustment for multiple comparisons. We found the epitope sieve effect in Step was driven by HLA A∗02:01; an allele which was found in low frequency in Phambili participants compared to Step participants. Furthermore, the coverage of the vaccine against subtype C Phambili viruses was 31%, 46% and 14% for Gag, Pol and Nef, respectively, compared to subtype B Step virus coverage of 56%, 61% and 26%, respectively. Discussion This study presents evidence of sieve effects in Gag and Nef; however could not confirm effects on specific amino acid sites. We propose that this weaker signal of vaccine immune pressure detected in the Phambili study compared to the Step study may have been influenced by differences in host genetics (HLA allele frequency) and reduced impact of vaccine-induced immune responses due to mismatch between the viral subtype in the vaccine and infecting subtypes.
subject
0Adenoviridae
1AIDS Vaccines - administration & dosage
2AIDS Vaccines - immunology
3Allergy and Immunology
4Amino acids
5Article
6Clinical trials
7Cohort Studies
8Cytotoxicity
9Double-Blind Method
10Epitopes - genetics
11Epitopes - immunology
12Female
13gag Gene Products, Human Immunodeficiency Virus - genetics
14gag Gene Products, Human Immunodeficiency Virus - immunology
15Gene Frequency
16Genomes
17Health aspects
18HIV (Viruses)
19HIV Infections - prevention & control
20HIV-1 - immunology
21HIV-1 vaccine
22HLA-A2 Antigen - genetics
23HLA-A2 Antigen - immunology
24Humans
25HVTN-503
26Immunity, Active
27Infections
28Lentivirus
29Lymphocytes
30Male
31Medical research
32Medicine, Experimental
33Methods
34nef Gene Products, Human Immunodeficiency Virus - genetics
35nef Gene Products, Human Immunodeficiency Virus - immunology
36Phambili
37Phylogenetics
38pol Gene Products, Human Immunodeficiency Virus - genetics
39pol Gene Products, Human Immunodeficiency Virus - immunology
40Proteins
41Sample Size
42Sieve analysis
43Step
44Vaccination Coverage
45Vaccines
46Vaccines, Synthetic - administration & dosage
47Vaccines, Synthetic - immunology
issn
00264-410X
11873-2518
fulltexttrue
rsrctypearticle
creationdate2016
recordtypearticle
recordideNqNk1tv1DAQhSMEoqXwE0CWeOEliy9x4gipqKqAVqoEEhfxZjnOuOttYi92UmnFn2dWuy20LyUvuZ3zeew5UxQvGV0wyuq3q8W1sdYHWHB8XdB2QWX1qDhkqhEll0w9Lg4pr6uyYvTnQfEs5xWlVArWPi0OeNPIulLysPh9QvI09xsSHdkDSx_62UJP_DjOAcg6Qc5zAhID6RKYq2mZ4ny5JD44sJOPIeMjmZZAvizN2PnBk_XSZCC8I2fnP0p2QybgnLfGbsiUvBmeF0-cGTK82N-Piu8fP3w7PSsvPn86Pz25KFmt1FQKVXMnG1lh1UI0lltp8GqbRlmooXaSN061jglXd5Q7AYK2kvWVqVTfdJ04Ko533PXcjdBbCFMyg14nP5q00dF4ffdP8Et9Ga-1RBCuiICzHSCuIRif4I63DzDp2GteN7pnVBkFRnS8sbLnWFDbi6oTrBKKNzWi3uxrSfHXDHnSo88WhsEEiHPWTOF6nAkm_kcqq1aKWqL09T3pKs4p4KFuVaIVSrYtqhY71aUZQGP3Iu4W22F6GL2NAZzH7ydVw7EA5KJB7gw2xZwTuNt9M6q3KdQrvW-t3qZQ01ZjCtH36t8Dv3XdxA4F7-6BrZ_MNkpYkR8exL_fuQFDc-0h6Ww9BIwstsZOuo_-QcLxPYIdfMBoDlewgfz38HTmmuqv20HazhGrBVUKp-gPYskX9A
startdate2016
enddate2016
creator
0Hertz, T
1Logan, M.G
2Rolland, M
3Magaret, C.A
4Rademeyer, C
5Fiore-Gartland, A
6Edlefsen, P.T
7DeCamp, A
8Ahmed, H
9Ngandu, N
10Larsen, B.B
11Frahm, N
12Marais, J
13Thebus, R
14Geraghty, D
15Hural, J
16Corey, L
17Kublin, J
18Gray, G
19McElrath, M.J
20Mullins, J.I
21Gilbert, P.B
22Williamson, C
general
0Elsevier Ltd
1Elsevier B.V
2Elsevier Limited
scope
0CGR
1CUY
2CVF
3ECM
4EIF
5NPM
6AAYXX
7CITATION
8BSHEE
93V.
107QL
117RV
127T2
137T5
147U9
157X7
167XB
1788C
1888E
198AO
208C1
218FE
228FH
238FI
248FJ
258FK
268G5
27ABUWG
28AZQEC
29BBNVY
30BENPR
31BHPHI
32C1K
33DWQXO
34FYUFA
35GHDGH
36GNUQQ
37GUQSH
38H94
39HCIFZ
40K9-
41K9.
42KB0
43LK8
44M0R
45M0S
46M0T
47M1P
48M2O
49M7N
50M7P
51MBDVC
52NAPCQ
53PQEST
54PQQKQ
55PQUKI
56Q9U
577X8
587U2
59BOBZL
60CLFQK
615PM
sort
creationdate2016
titleA study of vaccine-induced immune pressure on breakthrough infections in the Phambili phase 2b HIV-1 vaccine efficacy trial
authorHertz, T ; Logan, M.G ; Rolland, M ; Magaret, C.A ; Rademeyer, C ; Fiore-Gartland, A ; Edlefsen, P.T ; DeCamp, A ; Ahmed, H ; Ngandu, N ; Larsen, B.B ; Frahm, N ; Marais, J ; Thebus, R ; Geraghty, D ; Hural, J ; Corey, L ; Kublin, J ; Gray, G ; McElrath, M.J ; Mullins, J.I ; Gilbert, P.B ; Williamson, C
facets
frbrtype5
frbrgroupidcdi_FETCH-LOGICAL-1688t-3862f5754277337c2c5aaaa9778ce6e6f527f89f13f6b02f3e30951d4a48d7bb3
rsrctypearticles
prefilterarticles
languageeng
creationdate2016
topic
0Adenoviridae
1AIDS Vaccines - administration & dosage
2AIDS Vaccines - immunology
3Allergy and Immunology
4Amino acids
5Article
6Clinical trials
7Cohort Studies
8Cytotoxicity
9Double-Blind Method
10Epitopes - genetics
11Epitopes - immunology
12Female
13gag Gene Products, Human Immunodeficiency Virus - genetics
14gag Gene Products, Human Immunodeficiency Virus - immunology
15Gene Frequency
16Genomes
17Health aspects
18HIV (Viruses)
19HIV Infections - prevention & control
20HIV-1 - immunology
21HIV-1 vaccine
22HLA-A2 Antigen - genetics
23HLA-A2 Antigen - immunology
24Humans
25HVTN-503
26Immunity, Active
27Infections
28Lentivirus
29Lymphocytes
30Male
31Medical research
32Medicine, Experimental
33Methods
34nef Gene Products, Human Immunodeficiency Virus - genetics
35nef Gene Products, Human Immunodeficiency Virus - immunology
36Phambili
37Phylogenetics
38pol Gene Products, Human Immunodeficiency Virus - genetics
39pol Gene Products, Human Immunodeficiency Virus - immunology
40Proteins
41Sample Size
42Sieve analysis
43Step
44Vaccination Coverage
45Vaccines
46Vaccines, Synthetic - administration & dosage
47Vaccines, Synthetic - immunology
toplevel
0peer_reviewed
1online_resources
creatorcontrib
0Hertz, T
1Logan, M.G
2Rolland, M
3Magaret, C.A
4Rademeyer, C
5Fiore-Gartland, A
6Edlefsen, P.T
7DeCamp, A
8Ahmed, H
9Ngandu, N
10Larsen, B.B
11Frahm, N
12Marais, J
13Thebus, R
14Geraghty, D
15Hural, J
16Corey, L
17Kublin, J
18Gray, G
19McElrath, M.J
20Mullins, J.I
21Gilbert, P.B
22Williamson, C
collection
0Medline
1MEDLINE
2MEDLINE (Ovid)
3MEDLINE
4MEDLINE
5PubMed
6CrossRef
7Academic OneFile (A&I only)
8ProQuest Central (Corporate)
9Bacteriology Abstracts (Microbiology B)
10Nursing & Allied Health Database
11Health and Safety Science Abstracts (Full archive)
12Immunology Abstracts
13Virology and AIDS Abstracts
14Health & Medical Collection
15ProQuest Central (purchase pre-March 2016)
16Healthcare Administration Database (Alumni)
17Medical Database (Alumni Edition)
18ProQuest Pharma Collection
19Public Health Database
20ProQuest SciTech Collection
21ProQuest Natural Science Collection
22Hospital Premium Collection
23Hospital Premium Collection (Alumni Edition)
24ProQuest Central (Alumni) (purchase pre-March 2016)
25Research Library (Alumni Edition)
26ProQuest Central (Alumni Edition)
27ProQuest Central Essentials
28Biological Science Collection
29ProQuest Central
30Natural Science Collection
31Environmental Sciences and Pollution Management
32ProQuest Central Korea
33Health Research Premium Collection
34Health Research Premium Collection (Alumni)
35ProQuest Central Student
36Research Library Prep
37AIDS and Cancer Research Abstracts
38SciTech Premium Collection
39Consumer Health Database (Alumni Edition)
40ProQuest Health & Medical Complete (Alumni)
41Nursing & Allied Health Database (Alumni Edition)
42ProQuest Biological Science Collection
43Consumer Health Database
44Health & Medical Collection (Alumni Edition)
45Healthcare Administration Database
46Medical Database
47Research Library
48Algology Mycology and Protozoology Abstracts (Microbiology C)
49Biological Science Database
50Research Library (Corporate)
51Nursing & Allied Health Premium
52ProQuest One Academic Eastern Edition
53ProQuest One Academic
54ProQuest One Academic UKI Edition
55ProQuest Central Basic
56MEDLINE - Academic
57Safety Science and Risk
58OpenAIRE (Open Access)
59OpenAIRE
60PubMed Central (Full Participant titles)
jtitleVaccine
delivery
delcategoryRemote Search Resource
fulltextfulltext
addata
au
0Hertz, T
1Logan, M.G
2Rolland, M
3Magaret, C.A
4Rademeyer, C
5Fiore-Gartland, A
6Edlefsen, P.T
7DeCamp, A
8Ahmed, H
9Ngandu, N
10Larsen, B.B
11Frahm, N
12Marais, J
13Thebus, R
14Geraghty, D
15Hural, J
16Corey, L
17Kublin, J
18Gray, G
19McElrath, M.J
20Mullins, J.I
21Gilbert, P.B
22Williamson, C
formatjournal
genrearticle
ristypeJOUR
atitleA study of vaccine-induced immune pressure on breakthrough infections in the Phambili phase 2b HIV-1 vaccine efficacy trial
jtitleVaccine
addtitleVaccine
date2016
risdate2016
volume34
issue47
spage5792
epage5801
pages5792-5801
issn0264-410X
eissn1873-2518
notes
0Present address: Department of Biology, Emory University, Atlanta, GA 30322, United States.
1Present address: Department of Microbiology Immunology and Genetics and National Center for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
2Present address: Health Systems Research Unit, South African Medical Research Council, Cape Town 7505, South Africa.
abstractAbstract Introduction The Merck Adenovirus-5 Gag/Pol/Nef HIV-1 subtype-B vaccine evaluated in predominately subtype B epidemic regions (Step Study), while not preventing infection, exerted vaccine-induced immune pressure on HIV-1 breakthrough infections. Here we investigated if the same vaccine exerted immune pressure when tested in the Phambili Phase 2b study in a subtype C epidemic. Materials and methods A sieve analysis, which compares breakthrough viruses from placebo and vaccine arms, was performed on 277 near full-length genomes generated from 23 vaccine and 20 placebo recipients. Vaccine coverage was estimated by computing the percentage of 9-mers that were exact matches to the vaccine insert. Results There was significantly greater protein distances from the vaccine immunogen sequence in Gag (p = 0.045) and Nef (p = 0.021) in viruses infecting vaccine recipients compared to placebo recipients. Twenty-seven putative sites of vaccine-induced pressure were identified (p < 0.05) in Gag (n = 10), Pol (n = 7) and Nef (n = 10), although they did not remain significant after adjustment for multiple comparisons. We found the epitope sieve effect in Step was driven by HLA A∗02:01; an allele which was found in low frequency in Phambili participants compared to Step participants. Furthermore, the coverage of the vaccine against subtype C Phambili viruses was 31%, 46% and 14% for Gag, Pol and Nef, respectively, compared to subtype B Step virus coverage of 56%, 61% and 26%, respectively. Discussion This study presents evidence of sieve effects in Gag and Nef; however could not confirm effects on specific amino acid sites. We propose that this weaker signal of vaccine immune pressure detected in the Phambili study compared to the Step study may have been influenced by differences in host genetics (HLA allele frequency) and reduced impact of vaccine-induced immune responses due to mismatch between the viral subtype in the vaccine and infecting subtypes.
copNetherlands
pubElsevier Ltd
pmid27756485
doi10.1016/j.vaccine.2016.09.054
oafree_for_read