Cross reactivity of spike glycoprotein induced antibody against Delta and Omicron variants before and after third SARS-CoV-2 vaccine dose in healthy and immunocompromised individuals

Faustini, Sian; Shields, Adrian; Banham, Gemma D.; Wall, Nadezhda A.; Al-Taei, Saly; Tanner, Chloe; Ahmed, Zahra; Efstathiou, Elena; Townsend, Neal; Goodall, Margaret; Plant, Tim; Pérez-Toledo, Marisol; Jasiulewicz, Aleksandra; Price, Ruth K.; McLaughlin, James; Farnan, John; Moore, Julie; Robertson, Louise; Nesbit, Andrew; Curry, Grace; Black, Amy; Cunningham, Adam F.; Harper, Lorraine; Moore, Tara; Drayson, Mark T.; Richter, Alex

doi:10.1016/j.jinf.2022.01.002

Cited by 22 publications

(25 citation statements)

References 8 publications

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“…We demonstrate the feasibility of assigning international BAU to samples measured with our assays, and report similar levels of antibody to other laboratories who contributed to the development of international reference standards (20,30), allowing comparison of results from our assays with others. We deployed two of the screening assays (Spike and N Pan ELISA) on samples from a longitudinal cohort of healthcare workers in Bristol, UK (LOGIC).…”

Section: Discussionsupporting

confidence: 60%

Development and evaluation of low-volume tests to detect and characterise antibodies to SARS-CoV-2

Halliday

Long

Baum

et al. 2022

Preprint

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Low-volume antibody assays can be used to track SARS-CoV-2 infection rates in settings where active testing for virus is limited and remote sampling is optimal. We developed 12 ELISAs detecting total or antibody isotypes to SARS-CoV-2 nucleocapsid, spike protein or its receptor binding domain (RBD), 3 anti-RBD isotype specific luciferase immunoprecipitation system (LIPS) assays and a novel Spike-RBD bridging LIPS total-antibody assay. We utilised pre-pandemic (n=984) and confirmed/suspected recent COVID-19 sera taken pre-vaccination rollout in 2020 (n=269). Assays measuring total antibody discriminated best between pre-pandemic and COVID-19 sera and were selected for diagnostic evaluation. In the blind evaluation, two of these assays (Spike Pan ELISA and Spike-RBD Bridging LIPS assay) demonstrated >97% specificity and >92% sensitivity for samples from COVID-19 patients taken >21 days post symptom onset or PCR test. These assays offered better sensitivity for the detection of COVID-19 cases than a commercial assay which requires 100-fold larger serum volumes. This study demonstrates that low-volume in-house antibody assays can provide good diagnostic performance, and highlights the importance of using well-characterised samples and controls for all stages of assay development and evaluation. These cost-effective assays may be particularly useful for seroprevalence studies in low and middle-income countries.

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Section: Discussionsupporting

confidence: 60%

Development and evaluation of low-volume tests to detect and characterise antibodies to SARS-CoV-2

Halliday

Long

Baum

et al. 2022

Preprint

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show abstract

“…However, we have found that serological and cellular responses to the SARS-CoV-2 spike protein were positively incremented by the second vaccine dose, in keeping with previous studies in patients with inborn errors of immunity [ 16 ] suggesting potential benefit from further doses. Our group have demonstrated the effectiveness of a 3rd primary immunisation in raising antibody levels against the delta and omicron variants of concern in a cohort of immunocompromised renal dialysis patients and provide preliminary evidence of the benefit of a heterologous vaccination strategy on serological responses to vaccination [ 33 ]. Further studies will be necessary to explore whether different vaccination combinations (homologous/heterologous) or dosing schedules may improve responses and efficacy in patients with primary and secondary humoral immunodeficiencies.…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 Vaccine Responses in Individuals with Antibody Deficiency: Findings from the COV-AD Study

et al. 2022

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Background Vaccination prevents severe morbidity and mortality from COVID-19 in the general population. The immunogenicity and efficacy of SARS-CoV-2 vaccines in patients with antibody deficiency is poorly understood. Objectives COVID-19 in patients with antibody deficiency (COV-AD) is a multi-site UK study that aims to determine the immune response to SARS-CoV-2 infection and vaccination in patients with primary or secondary antibody deficiency, a population that suffers from severe and recurrent infection and does not respond well to vaccination. Methods Individuals on immunoglobulin replacement therapy or with an IgG less than 4 g/L receiving antibiotic prophylaxis were recruited from April 2021. Serological and cellular responses were determined using ELISA, live-virus neutralisation and interferon gamma release assays. SARS-CoV-2 infection and clearance were determined by PCR from serial nasopharyngeal swabs. Results A total of 5.6% (n = 320) of the cohort reported prior SARS-CoV-2 infection, but only 0.3% remained PCR positive on study entry. Seropositivity, following two doses of SARS-CoV-2 vaccination, was 54.8% (n = 168) compared with 100% of healthy controls (n = 205). The magnitude of the antibody response and its neutralising capacity were both significantly reduced compared to controls. Participants vaccinated with the Pfizer/BioNTech vaccine were more likely to be seropositive (65.7% vs. 48.0%, p = 0.03) and have higher antibody levels compared with the AstraZeneca vaccine (IgGAM ratio 3.73 vs. 2.39, p = 0.0003). T cell responses post vaccination was demonstrable in 46.2% of participants and were associated with better antibody responses but there was no difference between the two vaccines. Eleven vaccine-breakthrough infections have occurred to date, 10 of them in recipients of the AstraZeneca vaccine. Conclusion SARS-CoV-2 vaccines demonstrate reduced immunogenicity in patients with antibody deficiency with evidence of vaccine breakthrough infection.

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“…Antispike antibody titers greater than 141 binding antibody units (BAU) per milliliter are correlated with the presence of neutralizing antibodies (the most widely accepted marker of protection) against wild-type virus and the Alpha variant [3], but neutralization of the Delta and Omicron variants probably requires higher antibody titers. Recent results showed that there was evidence of significant waning of antibody reactivity against Delta and Omicron six months after the second dose of vaccine [4]. In this complementary study, we compared the concentrations of binding antibodies before breakthrough infections with Delta or Omicron SARS-CoV-2 variants.…”

Section: Dear Editormentioning

confidence: 99%

Antibody titers and breakthrough infections with Omicron SARS-CoV-2

Migueres¹,

Mansuy²,

Saivin³

et al. 2022

Journal of Infection

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Cross reactivity of spike glycoprotein induced antibody against Delta and Omicron variants before and after third SARS-CoV-2 vaccine dose in healthy and immunocompromised individuals

Cited by 22 publications

References 8 publications

Development and evaluation of low-volume tests to detect and characterise antibodies to SARS-CoV-2

Development and evaluation of low-volume tests to detect and characterise antibodies to SARS-CoV-2

SARS-CoV-2 Vaccine Responses in Individuals with Antibody Deficiency: Findings from the COV-AD Study

Antibody titers and breakthrough infections with Omicron SARS-CoV-2

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