Defining acceptable performance characteristics for SARS-CoV-2 serological tests requires factoring in how the results will be used.

BACKGROUND: CD4(+) T-cell enumeration (CD4 count) is used as a criterion to initiate antiretroviral therapy (ART) in HIV patients and to monitor treatment efficacy. However, simple, affordable, and reliable point-of-care (POC) instruments adapted to resource-limited settings are still lacking. The PIMA CD4 analyzer is a new POC instrument for CD4 counting that uses disposable cartridges and a battery-powered analyzer. METHODS: Whole blood samples were taken by venipuncture or by finger prick from 300 subjects, including HIV-infected patients and HIV (-) controls. CD4 counts were measured by PIMA (using venous or capillary blood) and by FACSCount (using venous blood) considered as the reference. RESULTS: Similar CD4 counts were obtained by PIMA and FACSCount using either HIV+ venous blood or HIV+ finger-prick blood samples. However, with a concordance coefficient of 0.88 and a Pearson correlation of 0.89, finger-prick blood performed not as good as venous blood (0.97 and 0.98, respectively). For a clinical decision to start ART at 200 CD4 cells per microliter, sensitivity of PIMA was 90%/91% and specificity 98%/96% for venous/finger-prick blood, respectively, and for a treatment threshold of 350 CD4 cells per microliter, the sensitivity was 98%/91% and the specificity was 79%/80% for venous/finger-prick blood, respectively. Repeatability (precision) on venous blood resulted in a coefficient of variation of 4%. Using finger-prick blood, the average instrument error frequency resulting in aborted analyses was 14%. CONCLUSIONS: PIMA is a good POC instrument for screening adult HIV-infected patients in resource-limited settings for treatment eligibility. Its performance on finger-prick blood is not as good as on venous blood. Adequate training for correct use of finger-prick blood samples is mandatory

The 2014 West African outbreak of Ebola virus disease highlighted the urgent need to develop an effective Ebola vaccine. We undertook 2 phase 1 studies assessing safety and immunogenicity of the viral vector modified vaccinia Ankara virus vectored Ebola Zaire vaccine (MVA-EBO-Z), manufactured rapidly on a new duck cell line either alone or in a heterologous prime-boost regimen with recombinant chimpanzee adenovirus type 3 vectored Ebola Zaire vaccine (ChAd3-EBO-Z) followed by MVA-EBO-Z. Adult volunteers in the United Kingdom (n = 38) and Senegal (n = 40) were vaccinated and an accelerated 1-week prime-boost regimen was assessed in Senegal. Safety was assessed by active and passive collection of local and systemic adverse events. The standard and accelerated heterologous prime-boost regimens were well-tolerated and elicited potent cellular and humoral immunogenicity in the United Kingdom and Senegal, but vaccine-induced antibody responses were significantly lower in Senegal. Cellular immune responses measured by flow cytometry were significantly greater in African vaccinees receiving ChAd3 and MVA vaccines in the same rather than the contralateral limb. MVA biomanufactured on an immortalized duck cell line shows potential for very large-scale manufacturing with lower cost of goods. This first trial of MVA-EBO-Z in humans encourages further testing in phase 2 studies, with the 1-week prime-boost interval regimen appearing to be particularly suitable for outbreak control. NCT02451891; NCT02485912.

CMV is associated with immunosenescence and reduced vaccine responses in the elderly (>70 yr). However, the impact of CMV in young adults is less clear. In this study, healthy UK and Senegalese adults aged 18–50 yr (average, 29 yr) were vaccinated with the Ebola vaccine candidate chimpanzee adenovirus type 3–vectored Ebola Zaire vaccine (ChAd3-EBO-Z) and boosted with modified vaccinia Ankara Ebola Zaire–vectored (MVA–EBO-Z) vaccine. CMV carriage was associated with an expansion of phenotypically senescent CD4⁺ and CD8⁺ T cells expressing CD57 and killer cell lectin-like receptor G1 (KLRG1), which was negatively associated with vaccine responses in both cohorts. Ebola-specific T cell responses induced by vaccination also contained significantly increased frequencies of terminally differentiated CD57⁺KLRG1⁺ cells in CMV seropositive (CMV⁺) individuals. This study suggests that CMV can also affect vaccine responses in younger adults and may have a particularly marked impact in many developing countries where CMV seroprevalence is almost universal.

CD4⁺ T-cell counts are used to screen and follow-up HIV-infected patients during treatment. As part of the World Health Organization prequalification program of diagnostics, we conducted an independent multicenter evaluation of the FACSCount CD4 and the Pima CD4, using the FACSCalibur as reference method. A total of 440 paired capillary and venous blood samples were collected from HIV-infected patients attending the HIV outpatient clinic in Antwerp, Belgium, and the HIV care and treatment center in Dar es Salam, Tanzania. Capillary blood was run on Pima analyzer, whereas venous blood was analyzed on FACSCount, Pima, and FACSCalibur instruments. Precision and agreement between methods were assessed. The FACSCount CD4 results were in agreement with the FACSCalibur results with relative bias of 0.4% and 3.1% on absolute CD4 counts and an absolute bias of -0.6% and -1.1% on CD4% in Antwerp and Dar es Salam, respectively. The Pima CD4 results were in agreement with the FACSCalibur results with relative bias of -4.1% and -9.4% using venous blood and of -9.5% and -0.9% using capillary blood in Antwerp and Dar es Salam, respectively. At the threshold of 350 cells per microliter, the FACSCount CD4 and Pima CD4 using venous and capillary blood misclassified 7%, 9%, and 13% of patients, respectively. The FACSCount CD4 provides reliable CD4 counts and CD4% and is suitable for monitoring adult and pediatric HIV patients in moderate-volume settings. The Pima CD4 is more suitable for screening eligible adult HIV patients for antiretroviral treatment initiation in low-volume laboratories.

The use of biomarkers to measure immune responses in serum is crucial for understanding population-level exposure and susceptibility to human pathogens. Advances in sample collection, multiplex testing, and computational modeling are transforming serosurveillance into a powerful tool for public health program design and response to infectious threats. In July 2018, 70 scientists from 16 countries met to perform a landscape analysis of approaches that support an integrated serosurveillance platform, including the consideration of issues for successful implementation. Here, we summarize the group’s insights and proposed roadmap for implementation, including objectives, technical requirements, ethical issues, logistical considerations, and monitoring and evaluation.