Antibody response against selected epitopes in the HIV-1 envelope gp41 ectodomain contributes to reduce viral burden in HIV-1 infected patients
Autor: | José Maria Marcelino, Kamal Mansinho, Robert Badura, Rute Marcelino, Emília Valadas, P. Brogueira, Cláudia Afonso, Luís Caldeira, Francisco Martin, Filipa Gramacho, Nuno Taveira, Nuno Janeiro |
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Přispěvatelé: | 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) |
Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
CD4-Positive T-Lymphocytes
Epidemiology Clinical Biochemistry HIV Infections HIV Antibodies Biochemistry Applied Microbiology and Biotechnology Epitope Epitopes Immunology and Microbiology (miscellaneous) Pharmacology (medical) HIV vaccine General Pharmacology Toxicology and Pharmaceutics Pharmacology Toxicology and Pharmaceutics (miscellaneous) Vaccines Multidisciplinary biology Viral Load HIV Envelope Protein gp41 Human Immunodeficiency Virus Vaccine Infectious Diseases Ectodomain Molecular Medicine Medicine Antibody Viral load Biotechnology Antigenicity Science General Biochemistry Genetics and Molecular Biology Immunology Gp41 Biochemistry Genetics and Molecular Biology (miscellaneous) Article SDG 3 - Good Health and Well-being Virology Genetics Humans General Molecular Biology General Immunology and Microbiology HIV Cell Biology CD4 Lymphocyte Count Viral replication biology.protein HIV-1 Neutralizing Antibodies |
Zdroj: | Scientific Reports, Vol 11, Iss 1, Pp 1-13 (2021) Scientific Reports Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP |
ISSN: | 2045-2322 |
Popis: | 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. |
Databáze: | OpenAIRE |
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