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HIV-1 superinfection can occur in the presence of broadly neutralizing antibodies

•We proposed that HIV superinfection occurs during low or narrow neutralizing antibodies.•Prior high titres and broadly neutralizing antibody responses did not prevent HIV superinfection.•There were clade associations in neutralization sensitivity; clade D viruses were the least sensitive.•Neutraliz... Full description

Journal Title: Vaccine 2018, Vol.36 (4), p.578-586
Main Author: Serwanga, Jennifer
Other Authors: Ssemwanga, Deogratius , Muganga, Michael , Nakiboneka, Ritah , Nakubulwa, Susan , Kiwuwa-Muyingo, Sylvia , Morris, Lynn , Redd, Andrew D. , Quinn, Thomas C. , Kaleebu, Pontiano , Mayanja, Yunia , Hermanus, Tandile , Ilmonen, Pauliina , Jonathan, Levin , Porcella, Stephen F.
Format: Electronic Article Electronic Article
Language: English
Subjects:
HIV
Sex
STD
Quelle: Alma/SFX Local Collection
Publisher: Netherlands: Elsevier Ltd
ID: ISSN: 0264-410X
Link: https://www.ncbi.nlm.nih.gov/pubmed/29274699
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recordid: cdi_proquest_miscellaneous_1980103491
title: HIV-1 superinfection can occur in the presence of broadly neutralizing antibodies
format: Article
creator:
  • Serwanga, Jennifer
  • Ssemwanga, Deogratius
  • Muganga, Michael
  • Nakiboneka, Ritah
  • Nakubulwa, Susan
  • Kiwuwa-Muyingo, Sylvia
  • Morris, Lynn
  • Redd, Andrew D.
  • Quinn, Thomas C.
  • Kaleebu, Pontiano
  • Mayanja, Yunia
  • Hermanus, Tandile
  • Ilmonen, Pauliina
  • Jonathan, Levin
  • Porcella, Stephen F.
subjects:
  • Acquired immune deficiency syndrome
  • AIDS
  • Analysis
  • Antibodies
  • Antibodies, Neutralizing - blood
  • Antibodies, Neutralizing - immunology
  • Broadly neutralizing antibodies
  • CD4 antigen
  • CD4 Lymphocyte Count
  • Clade A
  • Clade D
  • Female
  • Gene expression
  • Genotype
  • Health risks
  • HIV
  • HIV (Viruses)
  • HIV Antibodies - blood
  • HIV Antibodies - immunology
  • HIV Infections - immunology
  • HIV Infections - virology
  • HIV-1
  • HIV-1 - immunology
  • Human immunodeficiency virus
  • Humans
  • Immune response
  • Immunoglobulins
  • Infections
  • Lymphocytes
  • Lymphocytes T
  • Male
  • Neutralization
  • Neutralization Tests
  • Neutralizing
  • Plasma
  • Plasmas
  • Plasmids
  • Prostitution
  • Recombinants
  • Risk taking
  • Sex
  • Sexual behavior
  • Sexually transmitted diseases
  • STD
  • Superinfection
  • Superinfection - immunology
  • T cells
  • Trends
  • Values
  • Viral antibodies
  • Viruses
  • Workers
ispartof: Vaccine, 2018, Vol.36 (4), p.578-586
description: •We proposed that HIV superinfection occurs during low or narrow neutralizing antibodies.•Prior high titres and broadly neutralizing antibody responses did not prevent HIV superinfection.•There were clade associations in neutralization sensitivity; clade D viruses were the least sensitive.•Neutralizing antibody responses were negatively associated with concurrent CD4 T Cell counts.•Greater neutralisation breadths than those detected during natural infection might be needed to prevent HIV-1 superinfection. Superinfection of individuals already infected with HIV-1 suggests that pre-existing immune responses may not adequately protect against re-infection. We assessed high-risk female sex workers initially infected with HIV-1 clades A, D or A/D recombinants, to determine if HIV-1 broadly neutralizing antibodies were lacking prior to superinfection. Six superinfected female sex workers previously stratified by HIV-1 high-risk behavior, infecting virus clade and volunteer CD4 counts were evaluated at baseline (n = 5) and at 350 days post-superinfection (n = 6); one superinfected volunteer lacked pre-superinfection plasma. Retrospective plasmas were assessed for neutralization of a multi-clade panel of 12 HIV-1 viruses before superinfection, and then at quarterly intervals thereafter. Similarly stratified singly infected female sex workers were correspondingly assessed at baseline (n = 19) and 350 days after superinfection (n = 24). Neutralization of at least 50% of the 12 viruses (broad neutralization), and geometric means of the neutralization titers (IC50) were compared before and after superinfection; and were correlated with the volunteer HIV-1 superinfection status, CD4 counts, and pseudovirus clade. Preexisting broad neutralization occurred in 80% (4/5) of the superinfected subjects with no further broadening by 350 days after superinfection. In one of the five subjects, HIV-1 superinfection occurred when broad neutralization was lacking; with subsequent broadening of neutralizing antibodies occuring within 9 months and plateauing by 30 months after detection of superinfection. Clade B and C pseudoviruses were more sensitive to neutralization (13; [87%]); and (12; [80%]) than the locally circulating clades A (10; [67%]) and D (6; [40%]), respectively (p = 0.025). Low antibody titers correlated with clade D viruses and with >500 CD4 T cell counts, but not with the superinfection status. These data demonstrate that HIV-1 superinfection can occur both in the
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0264-410X
fulltext: fulltext
issn:
  • 0264-410X
  • 1873-2518
url: Link


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titleHIV-1 superinfection can occur in the presence of broadly neutralizing antibodies
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creatorSerwanga, Jennifer ; Ssemwanga, Deogratius ; Muganga, Michael ; Nakiboneka, Ritah ; Nakubulwa, Susan ; Kiwuwa-Muyingo, Sylvia ; Morris, Lynn ; Redd, Andrew D. ; Quinn, Thomas C. ; Kaleebu, Pontiano ; Mayanja, Yunia ; Hermanus, Tandile ; Ilmonen, Pauliina ; Jonathan, Levin ; Porcella, Stephen F.
creatorcontribSerwanga, Jennifer ; Ssemwanga, Deogratius ; Muganga, Michael ; Nakiboneka, Ritah ; Nakubulwa, Susan ; Kiwuwa-Muyingo, Sylvia ; Morris, Lynn ; Redd, Andrew D. ; Quinn, Thomas C. ; Kaleebu, Pontiano ; Mayanja, Yunia ; Hermanus, Tandile ; Ilmonen, Pauliina ; Jonathan, Levin ; Porcella, Stephen F. ; The HIV Superinfection Study Group ; HIV Superinfection Study Group
description•We proposed that HIV superinfection occurs during low or narrow neutralizing antibodies.•Prior high titres and broadly neutralizing antibody responses did not prevent HIV superinfection.•There were clade associations in neutralization sensitivity; clade D viruses were the least sensitive.•Neutralizing antibody responses were negatively associated with concurrent CD4 T Cell counts.•Greater neutralisation breadths than those detected during natural infection might be needed to prevent HIV-1 superinfection. Superinfection of individuals already infected with HIV-1 suggests that pre-existing immune responses may not adequately protect against re-infection. We assessed high-risk female sex workers initially infected with HIV-1 clades A, D or A/D recombinants, to determine if HIV-1 broadly neutralizing antibodies were lacking prior to superinfection. Six superinfected female sex workers previously stratified by HIV-1 high-risk behavior, infecting virus clade and volunteer CD4 counts were evaluated at baseline (n = 5) and at 350 days post-superinfection (n = 6); one superinfected volunteer lacked pre-superinfection plasma. Retrospective plasmas were assessed for neutralization of a multi-clade panel of 12 HIV-1 viruses before superinfection, and then at quarterly intervals thereafter. Similarly stratified singly infected female sex workers were correspondingly assessed at baseline (n = 19) and 350 days after superinfection (n = 24). Neutralization of at least 50% of the 12 viruses (broad neutralization), and geometric means of the neutralization titers (IC50) were compared before and after superinfection; and were correlated with the volunteer HIV-1 superinfection status, CD4 counts, and pseudovirus clade. Preexisting broad neutralization occurred in 80% (4/5) of the superinfected subjects with no further broadening by 350 days after superinfection. In one of the five subjects, HIV-1 superinfection occurred when broad neutralization was lacking; with subsequent broadening of neutralizing antibodies occuring within 9 months and plateauing by 30 months after detection of superinfection. Clade B and C pseudoviruses were more sensitive to neutralization (13; [87%]); and (12; [80%]) than the locally circulating clades A (10; [67%]) and D (6; [40%]), respectively (p = 0.025). Low antibody titers correlated with clade D viruses and with >500 CD4 T cell counts, but not with the superinfection status. These data demonstrate that HIV-1 superinfection can occur both in the presence, and in the absence of broadly neutralizing antibodies.
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0ISSN: 0264-410X
1EISSN: 1873-2518
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languageeng
publisherNetherlands: Elsevier Ltd
subjectAcquired immune deficiency syndrome ; AIDS ; Analysis ; Antibodies ; Antibodies, Neutralizing - blood ; Antibodies, Neutralizing - immunology ; Broadly neutralizing antibodies ; CD4 antigen ; CD4 Lymphocyte Count ; Clade A ; Clade D ; Female ; Gene expression ; Genotype ; Health risks ; HIV ; HIV (Viruses) ; HIV Antibodies - blood ; HIV Antibodies - immunology ; HIV Infections - immunology ; HIV Infections - virology ; HIV-1 ; HIV-1 - immunology ; Human immunodeficiency virus ; Humans ; Immune response ; Immunoglobulins ; Infections ; Lymphocytes ; Lymphocytes T ; Male ; Neutralization ; Neutralization Tests ; Neutralizing ; Plasma ; Plasmas ; Plasmids ; Prostitution ; Recombinants ; Risk taking ; Sex ; Sexual behavior ; Sexually transmitted diseases ; STD ; Superinfection ; Superinfection - immunology ; T cells ; Trends ; Values ; Viral antibodies ; Viruses ; Workers
ispartofVaccine, 2018, Vol.36 (4), p.578-586
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0Serwanga, Jennifer
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2Muganga, Michael
3Nakiboneka, Ritah
4Nakubulwa, Susan
5Kiwuwa-Muyingo, Sylvia
6Morris, Lynn
7Redd, Andrew D.
8Quinn, Thomas C.
9Kaleebu, Pontiano
10Mayanja, Yunia
11Hermanus, Tandile
12Ilmonen, Pauliina
13Jonathan, Levin
14Porcella, Stephen F.
15The HIV Superinfection Study Group
16HIV Superinfection Study Group
title
0HIV-1 superinfection can occur in the presence of broadly neutralizing antibodies
1Vaccine
addtitleVaccine
description•We proposed that HIV superinfection occurs during low or narrow neutralizing antibodies.•Prior high titres and broadly neutralizing antibody responses did not prevent HIV superinfection.•There were clade associations in neutralization sensitivity; clade D viruses were the least sensitive.•Neutralizing antibody responses were negatively associated with concurrent CD4 T Cell counts.•Greater neutralisation breadths than those detected during natural infection might be needed to prevent HIV-1 superinfection. Superinfection of individuals already infected with HIV-1 suggests that pre-existing immune responses may not adequately protect against re-infection. We assessed high-risk female sex workers initially infected with HIV-1 clades A, D or A/D recombinants, to determine if HIV-1 broadly neutralizing antibodies were lacking prior to superinfection. Six superinfected female sex workers previously stratified by HIV-1 high-risk behavior, infecting virus clade and volunteer CD4 counts were evaluated at baseline (n = 5) and at 350 days post-superinfection (n = 6); one superinfected volunteer lacked pre-superinfection plasma. Retrospective plasmas were assessed for neutralization of a multi-clade panel of 12 HIV-1 viruses before superinfection, and then at quarterly intervals thereafter. Similarly stratified singly infected female sex workers were correspondingly assessed at baseline (n = 19) and 350 days after superinfection (n = 24). Neutralization of at least 50% of the 12 viruses (broad neutralization), and geometric means of the neutralization titers (IC50) were compared before and after superinfection; and were correlated with the volunteer HIV-1 superinfection status, CD4 counts, and pseudovirus clade. Preexisting broad neutralization occurred in 80% (4/5) of the superinfected subjects with no further broadening by 350 days after superinfection. In one of the five subjects, HIV-1 superinfection occurred when broad neutralization was lacking; with subsequent broadening of neutralizing antibodies occuring within 9 months and plateauing by 30 months after detection of superinfection. Clade B and C pseudoviruses were more sensitive to neutralization (13; [87%]); and (12; [80%]) than the locally circulating clades A (10; [67%]) and D (6; [40%]), respectively (p = 0.025). Low antibody titers correlated with clade D viruses and with >500 CD4 T cell counts, but not with the superinfection status. These data demonstrate that HIV-1 superinfection can occur both in the presence, and in the absence of broadly neutralizing antibodies.
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1AIDS
2Analysis
3Antibodies
4Antibodies, Neutralizing - blood
5Antibodies, Neutralizing - immunology
6Broadly neutralizing antibodies
7CD4 antigen
8CD4 Lymphocyte Count
9Clade A
10Clade D
11Female
12Gene expression
13Genotype
14Health risks
15HIV
16HIV (Viruses)
17HIV Antibodies - blood
18HIV Antibodies - immunology
19HIV Infections - immunology
20HIV Infections - virology
21HIV-1
22HIV-1 - immunology
23Human immunodeficiency virus
24Humans
25Immune response
26Immunoglobulins
27Infections
28Lymphocytes
29Lymphocytes T
30Male
31Neutralization
32Neutralization Tests
33Neutralizing
34Plasma
35Plasmas
36Plasmids
37Prostitution
38Recombinants
39Risk taking
40Sex
41Sexual behavior
42Sexually transmitted diseases
43STD
44Superinfection
45Superinfection - immunology
46T cells
47Trends
48Values
49Viral antibodies
50Viruses
51Workers
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6Morris, Lynn
7Redd, Andrew D.
8Quinn, Thomas C.
9Kaleebu, Pontiano
10Mayanja, Yunia
11Hermanus, Tandile
12Ilmonen, Pauliina
13Jonathan, Levin
14Porcella, Stephen F.
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titleHIV-1 superinfection can occur in the presence of broadly neutralizing antibodies
authorSerwanga, Jennifer ; Ssemwanga, Deogratius ; Muganga, Michael ; Nakiboneka, Ritah ; Nakubulwa, Susan ; Kiwuwa-Muyingo, Sylvia ; Morris, Lynn ; Redd, Andrew D. ; Quinn, Thomas C. ; Kaleebu, Pontiano ; Mayanja, Yunia ; Hermanus, Tandile ; Ilmonen, Pauliina ; Jonathan, Levin ; Porcella, Stephen F.
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0Acquired immune deficiency syndrome
1AIDS
2Analysis
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4Antibodies, Neutralizing - blood
5Antibodies, Neutralizing - immunology
6Broadly neutralizing antibodies
7CD4 antigen
8CD4 Lymphocyte Count
9Clade A
10Clade D
11Female
12Gene expression
13Genotype
14Health risks
15HIV
16HIV (Viruses)
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18HIV Antibodies - immunology
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32Neutralization Tests
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34Plasma
35Plasmas
36Plasmids
37Prostitution
38Recombinants
39Risk taking
40Sex
41Sexual behavior
42Sexually transmitted diseases
43STD
44Superinfection
45Superinfection - immunology
46T cells
47Trends
48Values
49Viral antibodies
50Viruses
51Workers
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6Morris, Lynn
7Redd, Andrew D.
8Quinn, Thomas C.
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abstract•We proposed that HIV superinfection occurs during low or narrow neutralizing antibodies.•Prior high titres and broadly neutralizing antibody responses did not prevent HIV superinfection.•There were clade associations in neutralization sensitivity; clade D viruses were the least sensitive.•Neutralizing antibody responses were negatively associated with concurrent CD4 T Cell counts.•Greater neutralisation breadths than those detected during natural infection might be needed to prevent HIV-1 superinfection. Superinfection of individuals already infected with HIV-1 suggests that pre-existing immune responses may not adequately protect against re-infection. We assessed high-risk female sex workers initially infected with HIV-1 clades A, D or A/D recombinants, to determine if HIV-1 broadly neutralizing antibodies were lacking prior to superinfection. Six superinfected female sex workers previously stratified by HIV-1 high-risk behavior, infecting virus clade and volunteer CD4 counts were evaluated at baseline (n = 5) and at 350 days post-superinfection (n = 6); one superinfected volunteer lacked pre-superinfection plasma. Retrospective plasmas were assessed for neutralization of a multi-clade panel of 12 HIV-1 viruses before superinfection, and then at quarterly intervals thereafter. Similarly stratified singly infected female sex workers were correspondingly assessed at baseline (n = 19) and 350 days after superinfection (n = 24). Neutralization of at least 50% of the 12 viruses (broad neutralization), and geometric means of the neutralization titers (IC50) were compared before and after superinfection; and were correlated with the volunteer HIV-1 superinfection status, CD4 counts, and pseudovirus clade. Preexisting broad neutralization occurred in 80% (4/5) of the superinfected subjects with no further broadening by 350 days after superinfection. In one of the five subjects, HIV-1 superinfection occurred when broad neutralization was lacking; with subsequent broadening of neutralizing antibodies occuring within 9 months and plateauing by 30 months after detection of superinfection. Clade B and C pseudoviruses were more sensitive to neutralization (13; [87%]); and (12; [80%]) than the locally circulating clades A (10; [67%]) and D (6; [40%]), respectively (p = 0.025). Low antibody titers correlated with clade D viruses and with >500 CD4 T cell counts, but not with the superinfection status. These data demonstrate that HIV-1 superinfection can occur both in the presence, and in the absence of broadly neutralizing antibodies.
copNetherlands
pubElsevier Ltd
pmid29274699
doi10.1016/j.vaccine.2017.11.075
orcididhttps://orcid.org/0000-0001-9675-4234