Impact of HLA‐DRB1 allele polymorphisms on control of HIV infection in a Peruvian MSM cohort

Oriol-Tordera, Bruna; Llano, Anuska; Ganoza, Carmela; Cate, Steven; Hildebrand, William H.; Sánchez, Jorge; Calle, M. Luz; Berthou, Christian; Olvera, Àlex

doi:10.1111/tan.13085

Cited by 7 publications

(4 citation statements)

References 19 publications

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“…As for T cells, the natural T cell response to the entire HIV-1 proteome in an infected individual does not protect despite the wealth of data pointing to the CD8 + T cells’ ability to impose a selective pressure on HIV-111, 12, 13 as well as control experimental simian/simian-HIV (SIV/SHIV) infections14, 15 and association of some CD4 + T cell responses with HIV-1 disease control 16, 17, 18. It follows that the total T cell response cannot be easily correlated to a good clinical outcome, because not all naturally induced T cells are protective.…”

Section: Introductionmentioning

confidence: 99%

Parallel Induction of CH505 B Cell Ontogeny-Guided Neutralizing Antibodies and tHIVconsvX Conserved Mosaic-Specific T Cells against HIV-1

Wee

Moyo

Saunders

et al. 2019

Molecular Therapy - Methods & Clinical Development

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The aim of this work was to start collecting information on rational combination of antibody (Ab) and T cell vaccines into single regimens. Two promising candidate HIV-1 vaccine strategies, sequential isolates of CH505 virus Envs developed for initiation of broadly neutralizing antibody lineages and conserved-mosaic tHIVconsvX immunogens aiming to induce effective cross-clade T cell responses, were combined to assess vaccine interactions. These immunogens were delivered in heterologous vector/modality regimens consisting of non-replicating simian (chimpanzee) adenovirus ChAdOx1 (C), nonreplicating poxvirus MVA (M), and adjuvanted protein (P). Outbred CD1-SWISS mice were vaccinated intramuscularly using either parallel CM8M (tHIVconsvX)/CPPP (CH505) or sequential CM16M (tHIVconsvX)/CPPP (CH505) protocols, the latter of which delivered T cell CM prior to the CH505 Env. CM8M (tHIVconsvX) and CPPP or CMMP (CH505) vaccinations alone were included as comparators. The vaccine-elicited HIV-1-specific trimer-binding and neutralizing Abs and CD8 + /CD4 + T cell responses induced by the combined and comparator regimens were not statistically separable among regimens. The Ab-lineage immunogen strategy was particularly suited for combined regimens for its likely less potent induction of Env-specific T cell responses relative to homologous epitope-based vaccine strategies. These results inform design of the first rationally combined Ab and T cell vaccine regimens in human volunteers.

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Section: Introductionmentioning

confidence: 99%

Parallel Induction of CH505 B Cell Ontogeny-Guided Neutralizing Antibodies and tHIVconsvX Conserved Mosaic-Specific T Cells against HIV-1

Wee

Moyo

Saunders

et al. 2019

Molecular Therapy - Methods & Clinical Development

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“…In an overview, the alleles HLA-A*24 ( 9 ), A*36 ( 10 ), B*35 ( 11 ), B*53 ( 12 ), and DRB1*13 ( 13 ) are some associated with the progression of HIV infection. In contrast, the HLA-A*02 ( 14 ), B*27 ( 15 ), B*57 ( 16 ) and DRB1*15 ( 17 ) are examples associated with infection control.…”

Section: Introductionmentioning

confidence: 99%

HLA-B13, B35 and B*39 Alleles Are Closely Associated With the Lack of Response to ART in HIV Infection: A Cohort Study in a Population of Northern Brazil

et al. 2022

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IntroductionImmune reconstitution failure after HIV treatment is a multifactorial phenomenon that may also be associated with a single polymorphism of human leukocyte antigen (HLA); however, few reports include patients from the Brazilian Amazon. Our objective was to evaluate the association of the immunogenic profile of the “classical” HLA-I and HLA-II loci with treatment nonresponse in a regional cohort monitored over 24 months since HIV diagnosis.Materials and MethodsTreatment-free participants from reference centers in the state of Pará, Brazil, were enrolled. Infection screening was performed using enzyme immunoassays (Murex AG/AB Combination DiaSorin, UK) and confirmed by immunoblots (Bio-Manguinhos, FIOCRUZ). Plasma viral load was quantified by real-time PCR (ABBOTT, Chicago, Illinois, USA). CD4+/CD8+ T lymphocyte quantification was performed by immunophenotyping and flow cytometry (BD Biosciences, San Jose, CA, USA). Infection was monitored via test and logistics platforms (SISCEL and SICLOM). Therapeutic response failure was inferred based on CD4+ T lymphocyte quantification after 1 year of therapy. Loci A, B and DRB1 were genotyped using PCR-SSO (One Lambda Inc., Canoga Park, CA, USA). Statistical tests were applied using GENEPOP, GraphPad Prism 8.4.3 and BioEstat 5.3.ResultsOf the 270 patients monitored, 134 responded to treatment (CD4+ ≥ 500 cells/µL), and 136 did not respond to treatment (CD4+ < 500 cells/µL). The allele frequencies of the loci were similar to heterogeneous populations. The allelic profile of locus B was statistically associated with treatment nonresponse, and the B*13, B*35 and B*39 alleles had the greatest probabilistic influence. The B*13 allele had the highest risk of treatment nonresponse, and carriers of the allele had a detectable viral load and a CD4+ T lymphocyte count less than 400 cells/µL with up to 2 years of therapy. The B*13 allele was associated with a switch in treatment regimens, preferably to efavirenz (EFZ)-based regimens, and among those who switched regimens, half had a history of coinfection with tuberculosis.ConclusionsThe allelic variants of the B locus are more associated with non-response to therapy in people living with HIV (PLHIV) from a heterogeneous population in the Brazilian Amazon.

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“…10 As for T cells, the natural T cell response to the entire HIV-1 proteome in an infected individual does not protect despite the wealth of data pointing to the CD8 + T cells' ability to impose a selective pressure on HIV-1 [11][12][13] as well as control experimental simian/simian-HIV (SIV/SHIV) infections 14,15 and association of some CD4 + T cell responses with HIV-1 disease control. [16][17][18] It follows that the total T cell response cannot be easily correlated to a good clinical outcome, because not all naturally induced T cells are protective. After many years of research, the T cell field is coming to a realization that vaccine-elicited responses will need to be targeted toward particular vulnerable and, therefore, protective determinants on the virus, while avoiding as many as possible of the distractive non-protective "decoys."…”

Section: Introductionmentioning

confidence: 99%

Parallel Induction of CH505 B Cell Ontogeny-Guided Neutralizing Antibodies and tHIVconsvX Conserved Mosaic-Specific T Cells against HIV-1

Wee¹,

Moyo²,

Saunders³

et al. 2022

Molecular Therapy - Methods & Clinical Development

View full text Add to dashboard Cite

Impact of HLA‐DRB1 allele polymorphisms on control of HIV infection in a Peruvian MSM cohort

Cited by 7 publications

References 19 publications

Parallel Induction of CH505 B Cell Ontogeny-Guided Neutralizing Antibodies and tHIVconsvX Conserved Mosaic-Specific T Cells against HIV-1

Parallel Induction of CH505 B Cell Ontogeny-Guided Neutralizing Antibodies and tHIVconsvX Conserved Mosaic-Specific T Cells against HIV-1

HLA-B13, B35 and B*39 Alleles Are Closely Associated With the Lack of Response to ART in HIV Infection: A Cohort Study in a Population of Northern Brazil

Parallel Induction of CH505 B Cell Ontogeny-Guided Neutralizing Antibodies and tHIVconsvX Conserved Mosaic-Specific T Cells against HIV-1

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Impact of HLA‐DRB1 allele polymorphisms on control of HIV infection in a Peruvian MSM cohort

Cited by 7 publications

References 19 publications

Parallel Induction of CH505 B Cell Ontogeny-Guided Neutralizing Antibodies and tHIVconsvX Conserved Mosaic-Specific T Cells against HIV-1

Parallel Induction of CH505 B Cell Ontogeny-Guided Neutralizing Antibodies and tHIVconsvX Conserved Mosaic-Specific T Cells against HIV-1

HLA-B*13, B*35 and B*39 Alleles Are Closely Associated With the Lack of Response to ART in HIV Infection: A Cohort Study in a Population of Northern Brazil

Parallel Induction of CH505 B Cell Ontogeny-Guided Neutralizing Antibodies and tHIVconsvX Conserved Mosaic-Specific T Cells against HIV-1

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HLA-B13, B35 and B*39 Alleles Are Closely Associated With the Lack of Response to ART in HIV Infection: A Cohort Study in a Population of Northern Brazil