High avidity anti-integrase antibodies discriminate recent and non-recent HIV infection: Implications for HIV incidence assay

Tehrani, Zahra Rikhtegaran; Azadmanesh, Kayhan; Mostafavi, Ehsan; Gharibzadeh, Safoora; Soori, Shahrzad; Azizi, Mohammad; Khabiri, Alireza

doi:10.1016/j.jviromet.2017.12.003

Cited by 4 publications

(3 citation statements)

References 23 publications

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“…This can be best achieved by using tests that can detect recently infected individuals [5][6][7][8]. Considerable efforts and resources have been devoted to the development of laboratory assays to detect recent HIV-1 infections [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. However, only two of these assays, both developed in our laboratory, have been commercialized for specific application to estimate HIV-1 incidence in cross-sectional population: the BED-Capture Enzyme Immunoassay (BED-CEIA) [24] and the Limiting Antigen (LAg) Avidity EIA [17].…”

Section: Introductionmentioning

confidence: 99%

Performance evaluation of the Asante Rapid Recency Assay for verification of HIV diagnosis and detection of recent HIV-1 infections: Implications for epidemic control

Yufenyuy

Detorio

Dobbs

et al. 2022

PLOS Glob Public Health

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We previously described development of a rapid test for recent infection (RTRI) that can diagnose HIV infection and detect HIV-1 recent infections in a single device. This technology was transferred to a commercial partner as Asante Rapid Recency Assay (ARRA). We evaluated performance of the ARRA kits in the laboratory using a well-characterized panel of specimens. The plasma specimen panel (N = 1500) included HIV-1 (N = 570), HIV-2 (N = 10), and HIV-negatives (N = 920) representing multiple subtypes and geographic locations. Reference diagnostic data were generated using the Bio-Rad HIV-1-2-O EIA/Western blot algorithm with further serotyping performed using the Multispot HIV-1/2 assay. The LAg-Avidity EIA was used to generate reference data on recent and long-term infection for HIV-1 positive specimens at a normalized optical density (ODn) cutoff of 2.0 corresponding to a mean duration of about 6 months. All specimens were tested with ARRA according to the manufacturer’s recommendations. Test strips were also read for line intensities using a reader and results were correlated with visual interpretation. ARRA’s positive verification line (PVL) correctly classified 575 of 580 HIV-positive and 910 of 920 negative specimens resulting in a sensitivity of 99.1% (95% CI: 98.0–99.6) and specificity of 98.9% (95% CI: 98.1–99.4), respectively. The reader-based classification was similar for PVL with sensitivity of 99.3% (576/580) and specificity of 98.8% (909/920). ARRA’s long-term line (LTL) classified 109 of 565 HIV-1 specimens as recent and 456 as long-term compared to 98 as recent and 467 as long-term (LT) by LAg-Avidity EIA (cutoff ODn = 2.0), suggesting a mean duration of recent infection (MDRI) close to 6 months. Agreement of ARRA with LAg recent cases was 81.6% (80/98) and LT cases was 93.8% (438/467), with an overall agreement of 91.7% (kappa = 0.72). The reader (cutoff 2.9) classified 109/566 specimens as recent infections compared to 99 by the LAg-Avidity EIA for recency agreement of 81.8% (81/99), LT agreement of 9% (439/467) with overall agreement of 91.9% (kappa = 0.72). The agreement between visual interpretation and strip reader was 99.9% (95% CI: 99.6–99.9) for the PVL and 98.1% (95% CI: 96.6–98.9) for the LTL. ARRA performed well with HIV diagnostic sensitivity >99% and specificity >98%. Its ability to identify recent infections is comparable to the LA-Avidity EIA corresponding to an MDRI of about 6 months. This point-of-care assay has implications for real-time surveillance of new infections among newly diagnosed individuals for targeted prevention and interrupting ongoing transmission thus accelerating epidemic control.

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Section: Introductionmentioning

confidence: 99%

Performance evaluation of the Asante Rapid Recency Assay for verification of HIV diagnosis and detection of recent HIV-1 infections: Implications for epidemic control

Yufenyuy

Detorio

Dobbs

et al. 2022

PLOS Glob Public Health

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“…For example, strong reactivity to nuclear antigens is observed in Epstein Barr virus infection ( 49 ), and reactivity to the nucleocapsid protein is often used to evaluate prior SARS-CoV-2 infection ( 50 ). In HIV-infected individuals, integrase antibodies often appear after antibodies to other HIV targets ( 51 , 52 ). Intracellular antibody fragments directed against HIV integrase or its cellular target have been shown to inhibit viral replication ( 53 , 54 ).…”

Section: Discussionmentioning

confidence: 99%

HIV Antibody Profiles in HIV Controllers and Persons With Treatment-Induced Viral Suppression

et al. 2021

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IntroductionLow HIV viral load is associated with delayed disease progression and reduced HIV transmission. HIV controllers suppress viral load to low levels in the absence of antiretroviral treatment (ART). We used an antibody profiling system, VirScan, to compare antibody reactivity and specificity in HIV controllers, non-controllers with treatment-induced viral suppression, and viremic non-controllers.MethodsThe VirScan library contains 3,384 phage-displayed peptides spanning the HIV proteome. Antibody reactivity to these peptides was measured in plasma from a Discovery Cohort that included 13 elite controllers, 27 viremic controllers, 12 viremic non-controllers, and 21 non-controllers who were virally suppressed on ART. Antibody reactivity to selected peptides was also assessed in an independent cohort of 29 elite controllers and 37 non-controllers who were virally suppressed on ART (Validation Cohort) and in a longitudinal cohort of non-controllers.ResultsIn the Discovery Cohort, 62 peptides were preferentially targeted in HIV controllers compared to non-controllers who were virally suppressed on ART. These specificities were not significantly different when comparing controllers versus viremic non-controllers. Aggregate reactivity to these peptides was also high in elite controllers from the independent Validation Cohort. The 62 peptides formed seven clusters of homologous epitopes in env, gag, integrase, and vpu. Reactivity to one of these clusters located in gag p17 was inversely correlated with viral load set point in an independent cohort of non-controllers.ConclusionsAntibody reactivity was low in non-controllers suppressed on ART, but remained high in viremic controllers despite viral suppression. Antibodies in controllers and viremic non-controllers were directed against epitopes in diverse HIV proteins; higher reactivity against p17 peptides was associated with lower viral load set point. Further studies are needed to determine if these antibodies play a role in regulation of HIV viral load.

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“…Avidity measurement is important to monitor affinity maturation of the humoral response to vaccines and can aid in developing immunization strategies, such as using different engineered immunogens, adjuvants and routes, to guide pAb affinity maturation against desired protective epitopes ( 5 ). PAb avidity data is also used to measure the incidence of recent infections as low avidity antibodies are mounted after the onset of infection ( 6 , 7 ). Moreover, avidity measurements are immensely helpful in immune correlate analysis of vaccines as higher avidity antibodies may associate with protection ( 3 , 8 , 9 ).…”

Section: Introductionmentioning

confidence: 99%

A tool for evaluating heterogeneity in avidity of polyclonal antibodies

Dodds²,

Spreng³

et al. 2023

Front. Immunol.

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Diversity in specificity of polyclonal antibody (pAb) responses is extensively investigated in vaccine efficacy or immunological evaluations, but the heterogeneity in antibody avidity is rarely probed as convenient tools are lacking. Here we have developed a polyclonal antibodies avidity resolution tool (PAART) for use with label-free techniques, such as surface plasmon resonance and biolayer interferometry, that can monitor pAb-antigen interactions in real time to measure dissociation rate constant (kd) for defining avidity. PAART utilizes a sum of exponentials model to fit the dissociation time-courses of pAb-antigens interactions and resolve multiple kd contributing to the overall dissociation. Each kd value of pAb dissociation resolved by PAART corresponds to a group of antibodies with similar avidity. PAART is designed to identify the minimum number of exponentials required to explain the dissociation course and guards against overfitting of data by parsimony selection of best model using Akaike information criterion. Validation of PAART was performed using binary mixtures of monoclonal antibodies of same specificity but differing in kd of the interaction with their epitope. We applied PAART to examine the heterogeneity in avidities of pAb from malaria and typhoid vaccinees, and individuals living with HIV-1 that naturally control the viral load. In many cases, two to three kd were dissected indicating the heterogeneity of pAb avidities. We showcase examples of affinity maturation of vaccine induced pAb responses at component level and enhanced resolution of heterogeneity in avidity when antigen-binding fragments (Fab) are used instead of polyclonal IgG antibodies. The utility of PAART can be manifold in examining circulating pAb characteristics and could inform vaccine strategies aimed to guide the host humoral immune response.

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High avidity anti-integrase antibodies discriminate recent and non-recent HIV infection: Implications for HIV incidence assay

Cited by 4 publications

References 23 publications

Performance evaluation of the Asante Rapid Recency Assay for verification of HIV diagnosis and detection of recent HIV-1 infections: Implications for epidemic control

Performance evaluation of the Asante Rapid Recency Assay for verification of HIV diagnosis and detection of recent HIV-1 infections: Implications for epidemic control

HIV Antibody Profiles in HIV Controllers and Persons With Treatment-Induced Viral Suppression

A tool for evaluating heterogeneity in avidity of polyclonal antibodies

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