Antibody response against selected epitopes in the HIV-1 envelope gp41 ectodomain contributes to reduce viral burden in HIV-1 infected patients
Autor(a) principal: | |
---|---|
Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10362/130472 |
Resumo: | The ectodomain of gp41 is the target of potent binding and neutralizing antibodies (NAbs) and is being explored in new strategies for antibody-based HIV vaccines. Previous studies have suggested that the W164A-3S (3S) and EC26-2A4 (EC26) peptides located in the gp41 ectodomain may be potential HIV vaccine candidates. We assessed 3S- and EC26-specific binding antibody responses and related neutralizing activity in a large panel of chronic HIV-1-infected Portuguese individuals on ART. A similar proportion of participants had antibodies binding to 3S (9.6%) and EC26 (9.9%) peptides but the level of reactivity against 3S was significantly higher compared to EC26, except in the rare patients with double peptide reactivity. The higher antigenicity of 3S was unrelated with disease stage, as assessed by CD4+ T cell counts, but it was directly related with plasma viral load. Most patients that were tested (89.9%, N = 268) showed tier 1 neutralizing activity, the potency being inversely associated with plasma viral load. In the subset of patients that were tested for neutralization of tier 2 isolates, neutralization breadth was inversely correlated with plasma viral load and directly correlated with CD4+ T cell counts. These results are consistent with a role for neutralizing antibodies in controlling viral replication and preventing the decline of CD4+ T lymphocytes. Importantly, in patients with 3S-specific antibodies, neutralizing titers were inversely correlated with viral RNA levels and proviral DNA levels. Moreover, patients with 3S and/or EC26-specific antibodies showed a 1.9-fold higher tier 2 neutralization score than patients without antibodies suggesting that 3S and/or EC26-specific antibodies contribute to neutralization breadth and potency in HIV-1 infected patients. Overall, these results suggest that antibodies targeting the S3 and EC26 epitopes may contribute to reduce viral burden and provide further support for the inclusion of 3S and EC26 epitopes in HIV-1 vaccine candidates. |
id |
RCAP_e6f06d8d5490ab29463064ac39f3578c |
---|---|
oai_identifier_str |
oai:run.unl.pt:10362/130472 |
network_acronym_str |
RCAP |
network_name_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository_id_str |
7160 |
spelling |
Antibody response against selected epitopes in the HIV-1 envelope gp41 ectodomain contributes to reduce viral burden in HIV-1 infected patientsNeutralizing AntibodiesHuman Immunodeficiency Virus VaccineHIVGeneralBiochemistryBiochemistry, Genetics and Molecular Biology (miscellaneous)BiotechnologyCell BiologyClinical BiochemistryGeneral Biochemistry,Genetics and Molecular BiologyGeneticsMolecular BiologyMolecular MedicineApplied Microbiology and BiotechnologyGeneral Immunology and MicrobiologyImmunologyImmunology and Microbiology (miscellaneous)VirologyEpidemiologyInfectious DiseasesPharmacology (medical)General Pharmacology, Toxicology and PharmaceuticsPharmacology, Toxicology and Pharmaceutics (miscellaneous)SDG 3 - Good Health and Well-beingThe ectodomain of gp41 is the target of potent binding and neutralizing antibodies (NAbs) and is being explored in new strategies for antibody-based HIV vaccines. Previous studies have suggested that the W164A-3S (3S) and EC26-2A4 (EC26) peptides located in the gp41 ectodomain may be potential HIV vaccine candidates. We assessed 3S- and EC26-specific binding antibody responses and related neutralizing activity in a large panel of chronic HIV-1-infected Portuguese individuals on ART. A similar proportion of participants had antibodies binding to 3S (9.6%) and EC26 (9.9%) peptides but the level of reactivity against 3S was significantly higher compared to EC26, except in the rare patients with double peptide reactivity. The higher antigenicity of 3S was unrelated with disease stage, as assessed by CD4+ T cell counts, but it was directly related with plasma viral load. Most patients that were tested (89.9%, N = 268) showed tier 1 neutralizing activity, the potency being inversely associated with plasma viral load. In the subset of patients that were tested for neutralization of tier 2 isolates, neutralization breadth was inversely correlated with plasma viral load and directly correlated with CD4+ T cell counts. These results are consistent with a role for neutralizing antibodies in controlling viral replication and preventing the decline of CD4+ T lymphocytes. Importantly, in patients with 3S-specific antibodies, neutralizing titers were inversely correlated with viral RNA levels and proviral DNA levels. Moreover, patients with 3S and/or EC26-specific antibodies showed a 1.9-fold higher tier 2 neutralization score than patients without antibodies suggesting that 3S and/or EC26-specific antibodies contribute to neutralization breadth and potency in HIV-1 infected patients. Overall, these results suggest that antibodies targeting the S3 and EC26 epitopes may contribute to reduce viral burden and provide further support for the inclusion of 3S and EC26 epitopes in HIV-1 vaccine candidates.Instituto de Higiene e Medicina Tropical (IHMT)Global Health and Tropical Medicine (GHTM)TB, HIV and opportunistic diseases and pathogens (THOP)Individual Health Care (IHC)RUNMarcelino, RuteGramacho, FilipaMartin, FranciscoBrogueira, PedroJaneiro, NunoAfonso, ClaudiaBadura, RobertValadas, EmíliaMansinho, KamalCaldeira, LuísTaveira, NunoMarcelino, José M.2022-01-08T03:25:05Z2021-04-262021-04-26T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article13application/pdfhttp://hdl.handle.net/10362/130472eng2045-2322PURE: 33027943https://doi.org/10.1038/s41598-021-88274-9info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-05-22T17:57:58Zoai:run.unl.pt:10362/130472Portal AgregadorONGhttps://www.rcaap.pt/oai/openairemluisa.alvim@gmail.comopendoar:71602024-05-22T17:57:58Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Antibody response against selected epitopes in the HIV-1 envelope gp41 ectodomain contributes to reduce viral burden in HIV-1 infected patients |
title |
Antibody response against selected epitopes in the HIV-1 envelope gp41 ectodomain contributes to reduce viral burden in HIV-1 infected patients |
spellingShingle |
Antibody response against selected epitopes in the HIV-1 envelope gp41 ectodomain contributes to reduce viral burden in HIV-1 infected patients Marcelino, Rute Neutralizing Antibodies Human Immunodeficiency Virus Vaccine HIV General Biochemistry Biochemistry, Genetics and Molecular Biology (miscellaneous) Biotechnology Cell Biology Clinical Biochemistry General Biochemistry,Genetics and Molecular Biology Genetics Molecular Biology Molecular Medicine Applied Microbiology and Biotechnology General Immunology and Microbiology Immunology Immunology and Microbiology (miscellaneous) Virology Epidemiology Infectious Diseases Pharmacology (medical) General Pharmacology, Toxicology and Pharmaceutics Pharmacology, Toxicology and Pharmaceutics (miscellaneous) SDG 3 - Good Health and Well-being |
title_short |
Antibody response against selected epitopes in the HIV-1 envelope gp41 ectodomain contributes to reduce viral burden in HIV-1 infected patients |
title_full |
Antibody response against selected epitopes in the HIV-1 envelope gp41 ectodomain contributes to reduce viral burden in HIV-1 infected patients |
title_fullStr |
Antibody response against selected epitopes in the HIV-1 envelope gp41 ectodomain contributes to reduce viral burden in HIV-1 infected patients |
title_full_unstemmed |
Antibody response against selected epitopes in the HIV-1 envelope gp41 ectodomain contributes to reduce viral burden in HIV-1 infected patients |
title_sort |
Antibody response against selected epitopes in the HIV-1 envelope gp41 ectodomain contributes to reduce viral burden in HIV-1 infected patients |
author |
Marcelino, Rute |
author_facet |
Marcelino, Rute Gramacho, Filipa Martin, Francisco Brogueira, Pedro Janeiro, Nuno Afonso, Claudia Badura, Robert Valadas, Emília Mansinho, Kamal Caldeira, Luís Taveira, Nuno Marcelino, José M. |
author_role |
author |
author2 |
Gramacho, Filipa Martin, Francisco Brogueira, Pedro Janeiro, Nuno Afonso, Claudia Badura, Robert Valadas, Emília Mansinho, Kamal Caldeira, Luís Taveira, Nuno Marcelino, José M. |
author2_role |
author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Instituto de Higiene e Medicina Tropical (IHMT) Global Health and Tropical Medicine (GHTM) TB, HIV and opportunistic diseases and pathogens (THOP) Individual Health Care (IHC) RUN |
dc.contributor.author.fl_str_mv |
Marcelino, Rute Gramacho, Filipa Martin, Francisco Brogueira, Pedro Janeiro, Nuno Afonso, Claudia Badura, Robert Valadas, Emília Mansinho, Kamal Caldeira, Luís Taveira, Nuno Marcelino, José M. |
dc.subject.por.fl_str_mv |
Neutralizing Antibodies Human Immunodeficiency Virus Vaccine HIV General Biochemistry Biochemistry, Genetics and Molecular Biology (miscellaneous) Biotechnology Cell Biology Clinical Biochemistry General Biochemistry,Genetics and Molecular Biology Genetics Molecular Biology Molecular Medicine Applied Microbiology and Biotechnology General Immunology and Microbiology Immunology Immunology and Microbiology (miscellaneous) Virology Epidemiology Infectious Diseases Pharmacology (medical) General Pharmacology, Toxicology and Pharmaceutics Pharmacology, Toxicology and Pharmaceutics (miscellaneous) SDG 3 - Good Health and Well-being |
topic |
Neutralizing Antibodies Human Immunodeficiency Virus Vaccine HIV General Biochemistry Biochemistry, Genetics and Molecular Biology (miscellaneous) Biotechnology Cell Biology Clinical Biochemistry General Biochemistry,Genetics and Molecular Biology Genetics Molecular Biology Molecular Medicine Applied Microbiology and Biotechnology General Immunology and Microbiology Immunology Immunology and Microbiology (miscellaneous) Virology Epidemiology Infectious Diseases Pharmacology (medical) General Pharmacology, Toxicology and Pharmaceutics Pharmacology, Toxicology and Pharmaceutics (miscellaneous) SDG 3 - Good Health and Well-being |
description |
The ectodomain of gp41 is the target of potent binding and neutralizing antibodies (NAbs) and is being explored in new strategies for antibody-based HIV vaccines. Previous studies have suggested that the W164A-3S (3S) and EC26-2A4 (EC26) peptides located in the gp41 ectodomain may be potential HIV vaccine candidates. We assessed 3S- and EC26-specific binding antibody responses and related neutralizing activity in a large panel of chronic HIV-1-infected Portuguese individuals on ART. A similar proportion of participants had antibodies binding to 3S (9.6%) and EC26 (9.9%) peptides but the level of reactivity against 3S was significantly higher compared to EC26, except in the rare patients with double peptide reactivity. The higher antigenicity of 3S was unrelated with disease stage, as assessed by CD4+ T cell counts, but it was directly related with plasma viral load. Most patients that were tested (89.9%, N = 268) showed tier 1 neutralizing activity, the potency being inversely associated with plasma viral load. In the subset of patients that were tested for neutralization of tier 2 isolates, neutralization breadth was inversely correlated with plasma viral load and directly correlated with CD4+ T cell counts. These results are consistent with a role for neutralizing antibodies in controlling viral replication and preventing the decline of CD4+ T lymphocytes. Importantly, in patients with 3S-specific antibodies, neutralizing titers were inversely correlated with viral RNA levels and proviral DNA levels. Moreover, patients with 3S and/or EC26-specific antibodies showed a 1.9-fold higher tier 2 neutralization score than patients without antibodies suggesting that 3S and/or EC26-specific antibodies contribute to neutralization breadth and potency in HIV-1 infected patients. Overall, these results suggest that antibodies targeting the S3 and EC26 epitopes may contribute to reduce viral burden and provide further support for the inclusion of 3S and EC26 epitopes in HIV-1 vaccine candidates. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-04-26 2021-04-26T00:00:00Z 2022-01-08T03:25:05Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10362/130472 |
url |
http://hdl.handle.net/10362/130472 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2045-2322 PURE: 33027943 https://doi.org/10.1038/s41598-021-88274-9 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
13 application/pdf |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
mluisa.alvim@gmail.com |
_version_ |
1817545836726321152 |