Development of an avidity assay for detection of recent HIV infections

Shepherd, Samantha J.; McAllister, Georgina; Kean, Joy; Wallace, Lesley; Templeton, Kate; Goldberg, David J.; Gunson, Rory

doi:10.1016/j.jviromet.2015.02.016

Cited by 13 publications

(8 citation statements)

References 23 publications

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“…Plates were analyzed on a spectrophotometer and optical density was measured at 450 nm. The avidity index was calculated by taking the OD450 value of the urea treated well divided by the untreated well, as previously described [40,41].…”

Section: Avidity Analysismentioning

confidence: 99%

“…Affinity maturation is a critical component of the germinal center reaction and results in the induction of high affinity antibodies [47,48]. An avidity analysis, utilizing chaotropic agents such as urea can be used to interrogate the affinity of the antibody response, by measuring how tightly antibodies bind to a given antigen in the presence of a disassociating chaotropic agent [40,41]. The avidity index describes the percentage of reactivity remaining after treatment with urea [49].…”

Section: Ctla-4 Blockade Induces High Avidity Hiv-specific Antibodiesmentioning

confidence: 99%

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CTLA-4 Blockade, during HIV Virus-Like Particles Immunization, Alters HIV-Specific B-Cell Responses

et al. 2020

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Studies have shown that blockade of CTLA-4 promoted the expansion of germinal center B-cells in viral infection or immunization with model antigens. Few studies have evaluated the immunological consequences of CTLA-4 blockade during immunization against relevant vaccine candidates. Here, we investigated the effects of CTLA-4 blockade on HIV virus-like particles (VLPs) vaccination in a C57BL/6J mouse model. We found that CTLA-4 blockade during HIV VLP immunization resulted in increased CD4+ T-cell activation, promoted the expansion of HIV envelope (Env)-specific follicular helper T cell (Tfh) cells, and significantly increased HIV Gag- and Env-specific IgG with higher avidity and antibody-dependent cellular cytotoxicity (ADCC) capabilities. Furthermore, after only a single immunization, CTLA-4 blockade accelerated T-cell dependent IgG class switching and the induction of significantly high serum levels of the B-cell survival factor, A proliferation-inducing ligand (APRIL). Although no significant increase in neutralizing antibodies was observed, increased levels of class-switched Env- and Gag-specific IgG are indicative of increased polyclonal B-cell activation, which demonstrated the ability to mediate and enhance ADCC in this study. Altogether, our findings show that CTLA-4 blockade can increase the levels of HIV antigen-specific B-cell and antigen-specific Tfh cell activity and impact humoral immune responses when combined with a clinically relevant HIV VLP-based vaccine.

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Section: Avidity Analysismentioning

confidence: 99%

Section: Ctla-4 Blockade Induces High Avidity Hiv-specific Antibodiesmentioning

confidence: 99%

CTLA-4 Blockade, during HIV Virus-Like Particles Immunization, Alters HIV-Specific B-Cell Responses

et al. 2020

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“…The HIV viral load using the Abbott RealTi m e HIV-1 was 195 328 copies ml −1 . Using an in-house avidity assay the HIV avidity was low (20 %) indicating that the patient had a recent infection within the past three to four months [ 9 ]. The CD4 count was 730 cells mm − 3 .…”

Section: Investigationsmentioning

confidence: 99%

HIV positive patient with GBS-like syndrome

Shepherd¹,

Black

Thomson

et al. 2017

JMM Case Reports

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Introduction. Guillain–Barré Syndrome (GBS) is an acute demyelinating polyneuropathy which can occur post-infection. Criteria of diagnosis of GBS include areflexia with progressive bilateral weakness in arms and legs. GBS can lead to severe respiratory and cardiac complications. The fatality rate can be up to 5 % in patients, depending on the severity of the symptoms. HIV can cause a range of neurological disorders including, on rare occasions, GBS. GBS can occur at any stage of HIV infection, highlighting the complexity of diagnosis of GBS within HIV patients.Case presentation. A 57 year old female with lumbar back pain radiating to the legs, poor mobility and tiredness, with reports of a viral-like illness four days previously, was initially diagnosed with a lower respiratory tract infection and discharged. Seventeen days later the patient was readmitted to hospital with progressive lower and upper limb weakness, areflexia and sensory loss. She was diagnosed with GBS and was unexpectedly discovered to be HIV-positive. HIV avidity was low indicating a recently acquired HIV infection. The patient was treated with intravenous immunoglobulin for five days for the GBS and commenced antriretrovirals for HIV. The patient was discharge from hospital 53 days after admission with walking aids and regular physiotherapy follow-up.Conclusion. This case highlighted the need for all clinicians to be aware that patients with symptoms of GBS, regardless of clinical history should be offered an HIV test. GBS can be the first sign a patient is HIV-positive.

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“…The AI was calculated by dividing the optical density (OD) of the DEA-treated well by the OD of the nontreated well for the same sample and multiplying by 100. 30 Samples were classified as assay positive or assay negative based on the AI cutoff. Additionally, any sample where the wash buffer well OD was <1.0 was classified as assay positive.…”

Section: Laboratory Methodsmentioning

confidence: 99%

Development and Evaluation of a Modified Fourth-Generation Human Immunodeficiency Virus Enzyme Immunoassay for Cross-Sectional Incidence Estimation in Clade B Populations

Kirkpatrick

Patel

Celum

et al. 2016

AIDS Research and Human Retroviruses

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Background: Accurate methods for cross-sectional incidence estimation are needed for HIV surveillance and prevention research. We developed an avidity assay based on the fourth-generation Genetic Systems HIV Combo Ag/Ab EIA (Bio-Rad Combo assay) and evaluated its performance. Materials and Methods: The BioRad Combo assay was modified incubating samples with and without 0.025 M diethylamine (DEA). The avidity index (AI) was calculated as the ratio of the DEA-treated to untreated result for a specific sample. We analyzed 2,140 samples from 808 individuals from the United States with known duration of HIV infection. The mean duration of recent infection (MDRI) and the false-recent rate (FRR, fraction of samples from individuals known to be infected >2 years misclassified as recent) were calculated for AI cutoffs of 20%-90% for the avidity assay alone and in combination with a viral load assay (VL, limit of detection 400 copies/ml). Factors associated with misclassification of samples collected ‡2 years after infections were also evaluated. Results: The MDRI for the Bio-Rad Combo Avidity assay ranged from 50 days using an AI cutoff of 20% to 276 days using an AI cutoff of 90%; the FRR ranged from 0% to 9%. When samples with a VL <400 copies/ml were classified as nonrecent, the FRRs were reduced approximately twofold and the MDRI estimates were reduced by *20%. An AI cutoff of 50% provided an MDRI of 135 days with an FRR of 2.1%. All samples from elite suppressors had an AI >80%. In adjusted analysis, viral suppression and low CD4 cell count were significantly associated with misclassification among individuals infected >2 years. Conclusions: This modified Bio-Rad Combo Avidity assay may be a useful tool for cross-sectional HIV incidence estimation. Further research is needed to evaluate use of this assay in combination with other assays to accurately estimate population-level HIV incidence.

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Development of an avidity assay for detection of recent HIV infections

Cited by 13 publications

References 23 publications

CTLA-4 Blockade, during HIV Virus-Like Particles Immunization, Alters HIV-Specific B-Cell Responses

CTLA-4 Blockade, during HIV Virus-Like Particles Immunization, Alters HIV-Specific B-Cell Responses

HIV positive patient with GBS-like syndrome

Development and Evaluation of a Modified Fourth-Generation Human Immunodeficiency Virus Enzyme Immunoassay for Cross-Sectional Incidence Estimation in Clade B Populations

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