Cross-Reactive Antibodies With the Capacity to Mediate HIV-1 Envelope Glycoprotein–Targeted Antibody-Dependent Cellular Cytotoxicity Identified in HIV-2–Infected Individuals

Karlsson, Ingrid; Tingstedt, Jeanette Linnea; Şahin, Gülşen Özkaya; Hansen, Mikkel Fougt; Szojka, Zsófia Ilona; Buggert, Marcus; Biague, Antonio; Silva, Zacharias Da; Månsson, Fredrik; Esbjörnsson, Joakim; Norrgren, Hans; Medstrand, Patrik; Fomsgaard, Anders; Jansson, Marianne

doi:10.1093/infdis/jiz001

Cited by 7 publications

(7 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Collected blood samples has enabled in-depth studies of virological and immunological correlates of HIV-1 and HIV-2-related disease [3,[27][28][29][30][31][32][33][34][35][36][37][38].…”

Section: The Police Cohortmentioning

confidence: 99%

HIV treatment in Guinea-Bissau: room for improvement and time for new treatment options

et al. 2020

View full text Add to dashboard Cite

Despite advances in the treatment quality of HIV throughout the world, several countries are still facing numerous obstacles in delivering HIV treatment at a sufficiently high quality, putting patients’ lives in jeopardy. The aim of this status article is to give an overview of HIV treatment outcomes in the West African country, Guinea-Bissau, and to assess how newer treatment strategies such as long-acting injectable drugs or an HIV cure may limit or stop the HIV epidemic in this politically unstable and low-resource setting. Several HIV cohorts in Guinea-Bissau have been established and are used as platforms for epidemiological, virological, immunological and clinical studies often with a special focus on HIV-2, which is prevalent in the country. The Bandim Health Project, a demographic surveillance site, has performed epidemiological HIV surveys since 1987 among an urban population in the capital Bissau. The Police cohort, an occupational cohort of police officers, has enabled analyses of persons seroconverting with estimated times of seroconversion among HIV-1 and HIV-2-infected individuals, allowing incidence measurements while the Bissau HIV Cohort and a newer Nationwide HIV Cohort have provided clinical data on large numbers of HIV-infected patients. The HIV cohorts in Guinea-Bissau are unique platforms for research and represent real life in many African countries. Poor adherence, lack of HIV viral load measurements, inadequate laboratory facilities, high rates of loss to follow-up, mortality, treatment failure and resistance development, are just some of the challenges faced putting the goal of “90–90–90″ for Guinea-Bissau well out of reach by 2020. Maintaining undetectable viral loads on treatment as a prerequisite of a cure strategy seems not possible at the moment. Thinking beyond one-pill-once-a-day, long-acting antiretroviral treatment options such as injectable drugs or implants may be a better treatment option in settings like Guinea-Bissau and may even pave the way for an HIV cure. If the delivery of antiretroviral treatment in sub-Saharan Africa in a sustainable way for the future should be improved by focusing on existing treatment options or through focusing on new treatment options remains to be determined.

show abstract

“…Collected blood samples has enabled in-depth studies of virological and immunological correlates of HIV-1 and HIV-2-related disease [3,[27][28][29][30][31][32][33][34][35][36][37][38].…”

Section: The Police Cohortmentioning

confidence: 99%

HIV treatment in Guinea-Bissau: room for improvement and time for new treatment options

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Fc-mediated effector functions, such as the effect of complement on antibody antiviral activity, have also been reported to be potent in HIV-2 infection [76]. In addition, antibodies with a broad ability to mediate antibody dependent cellular cytotoxicity (ADCC), and even cross-react with HIV-1, are found in HIV-2 infected individuals [83, 84]. Thus, despite low-level viraemia, strong antibody responses in HIV-2 infection are sustained during both asymptomatic and progressive HIV-2 infections and do not distinguish between patient groups in different disease stages [79].…”

Section: Hiv-1 and Hiv-2 Virology And Immunologymentioning

confidence: 99%

“…Despite recent disappointments on the possibility of LRAs leading to longstanding remission in HIV-1, there could be a case for trying LRAs and “shock-and-kill” therapies in HIV-2, since it may be a less fit and more sensitive virus. HIV-2 cytotoxic CD8+ T-cell responses and possibly antibody responses, either broadly neutralizing or mediating ADCC, may partly explain the delayed progression of HIV-1 in patients firstly infected with HIV-2 and later superinfected with HIV-1 [56, 59, 77–79, 84, 98, 99, 119–123]. Hence, if HIV-2 immune responses play a role in controlling the rate of HIV-1 disease progression in individuals with dual-infection, it is plausible that boosting immunity may be able to induce relapse-free remission in HIV-2.…”

Section: Current Functional Cure Strategies and The Possibility Of Sumentioning

confidence: 99%

“…This trial unit has the capacity to handle 10–20 annual project visits that such trials may entail, as well as provide complex treatments requiring long infusions. The set-up for advanced analyses of immune-mediated processes is in place, both locally and among external partners [65, 71, 73–77, 80, 84, 119, 127–129]. Finally, more collaborations are needed in order to fully take on the many possibilities within this emerging field of HIV-2 cure research, and the Bissau cohorts are open to any collaborative efforts in this area and possible HIV cure applications.…”

Section: Current Functional Cure Strategies and The Possibility Of Sumentioning

confidence: 99%

See 1 more Smart Citation

HIV-2 as a model to identify a functional HIV cure

et al. 2019

Self Cite

View full text Add to dashboard Cite

Two HIV virus types exist: HIV-1 is pandemic and aggressive, whereas HIV-2 is confined mainly to West Africa and less pathogenic. Despite the fact that it has been almost 40 years since the discovery of AIDS, there is still no cure or vaccine against HIV. Consequently, the concepts of functional vaccines and cures that aim to limit HIV disease progression and spread by persistent control of viral replication without life-long treatment have been suggested as more feasible options to control the HIV pandemic. To identify virus-host mechanisms that could be targeted for functional cure development, researchers have focused on a small fraction of HIV-1 infected individuals that control their infection spontaneously, so-called elite controllers. However, these efforts have not been able to unravel the key mechanisms of the infection control. This is partly due to lack in statistical power since only 0.15% of HIV-1 infected individuals are natural elite controllers. The proportion of long-term viral control is larger in HIV-2 infection compared with HIV-1 infection. We therefore present the idea of using HIV-2 as a model for finding a functional cure against HIV. Understanding the key differences between HIV-1 and HIV-2 infections, and the cross-reactive effects in HIV-1/HIV-2 dual-infection could provide novel insights in developing functional HIV cures and vaccines.

show abstract

“…Furthermore, potent and sustainable humoral (9)(10)(11) and cellular (12)(13)(14)(15) immune responses are elicited during HIV-2 infection. HIV-2 has also been shown to delay subsequent HIV-1 disease progression during dual HIV-1/2 (HIV-D) infection (16,17), and HIV-1 cross-reactive immunity in HIV-2-infected individuals has been reported (18)(19)(20)(21). Still, HIV-2-infected individuals, can develop immunodeficiency despite low or undetectable viremia (22), and AIDS onset occurs at higher CD4 T-cell levels (3,23).…”

Section: Introductionmentioning

confidence: 99%

Inverted CD8 T-Cell Exhaustion and Co-Stimulation Marker Balance Differentiate Aviremic HIV-2-Infected From Seronegative Individuals

et al. 2021

Self Cite

View full text Add to dashboard Cite

HIV-2 is less pathogenic compared to HIV-1. Still, disease progression may develop in aviremic HIV-2 infection, but the driving forces and mechanisms behind such development are unclear. Here, we aimed to reveal the immunophenotypic pattern associated with CD8 T-cell pathology in HIV-2 infection, in relation to viremia and markers of disease progression. The relationships between pathological differences of the CD8 T-cell memory population and viremia were analyzed in blood samples obtained from an occupational cohort in Guinea-Bissau, including HIV-2 viremic and aviremic individuals. For comparison, samples from HIV-1- or dually HIV-1/2-infected and seronegative individuals were obtained from the same cohort. CD8 T-cell exhaustion was evaluated by the combined expression patterns of activation, stimulatory and inhibitory immune checkpoint markers analyzed using multicolor flow cytometry and advanced bioinformatics. Unsupervised multidimensional clustering analysis identified a cluster of late differentiated CD8 T-cells expressing activation (CD38+, HLA-DRint/high), co-stimulatory (CD226+/-), and immune inhibitory (2B4+, PD-1high, TIGIThigh) markers that distinguished aviremic from viremic HIV-2, and treated from untreated HIV-1-infected individuals. This CD8 T-cell population displayed close correlations to CD4%, viremia, and plasma levels of IP-10, sCD14 and beta-2 microglobulin in HIV-2 infection. Detailed analysis revealed that aviremic HIV-2-infected individuals had higher frequencies of exhausted TIGIT+ CD8 T-cell populations lacking CD226, while reduced percentage of stimulation-receptive TIGIT-CD226+ CD8 T-cells, compared to seronegative individuals. Our results suggest that HIV-2 infection, independent of viremia, skews CD8 T-cells towards exhaustion and reduced co-stimulation readiness. Further knowledge on CD8 T-cell phenotypes might provide help in therapy monitoring and identification of immunotherapy targets.

show abstract

Cross-Reactive Antibodies With the Capacity to Mediate HIV-1 Envelope Glycoprotein–Targeted Antibody-Dependent Cellular Cytotoxicity Identified in HIV-2–Infected Individuals

Cited by 7 publications

References 15 publications

HIV treatment in Guinea-Bissau: room for improvement and time for new treatment options

HIV treatment in Guinea-Bissau: room for improvement and time for new treatment options

HIV-2 as a model to identify a functional HIV cure

Inverted CD8 T-Cell Exhaustion and Co-Stimulation Marker Balance Differentiate Aviremic HIV-2-Infected From Seronegative Individuals

Contact Info

Product

Resources

About