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1.
Euro Surveill ; 27(1)2022 01.
Article in English | MEDLINE | ID: covidwho-1613512

ABSTRACT

Serum samples were collected pre- and post-booster vaccination with Comirnaty in 626 participants (aged ≥ 50 years) who had received two Comirnaty doses < 30 days apart, two Comirnaty doses ≥ 30 days apart or two Vaxzevria doses ≥ 30 days apart. Irrespective of primary vaccine type or schedule, spike antibody GMTs peaked 2-4 weeks after second dose, fell significantly ≤ 38 weeks later and rose above primary immunisation GMTs 2-4 weeks post-booster. Higher post-booster responses were observed with a longer interval between primary immunisation and boosting.


Subject(s)
COVID-19 Vaccines , COVID-19 , Humans , London , SARS-CoV-2 , United Kingdom
2.
Microbiol Spectr ; : e0078621, 2022 Jan 05.
Article in English | MEDLINE | ID: covidwho-1605388

ABSTRACT

Seroepidemiological studies to monitor antibody kinetics are important for assessing the extent and spread of SARS-CoV-2 in a population. Noninvasive sampling methods are advantageous for reducing the need for venipuncture, which may be a barrier to investigations, particularly in pediatric populations. Oral fluids are obtained by gingiva-crevicular sampling from children and adults and are very well accepted. Enzyme immunoassays (EIAs) based on these samples have acceptable sensitivity and specificity compared to conventional serum-based antibody EIAs and are suitable for population-based surveillance. We describe the development and evaluation of SARS-CoV-2 IgG EIAs using SARS-CoV-2 viral nucleoprotein (NP) and spike (S) proteins in IgG isotype capture format and an indirect receptor-binding-domain (RBD) IgG EIA, intended for use in children as a primary endpoint. All three assays were assessed using a panel of 1,999 paired serum and oral fluids from children and adults participating in school SARS-CoV-2 surveillance studies during and after the first and second pandemic wave in the United Kingdom. The anti-NP IgG capture assay was the best candidate, with an overall sensitivity of 75% (95% confidence interval [CI]: 71 to 79%) and specificity of 99% (95% CI: 78 to 99%) compared with paired serum antibodies. Sensitivity observed in children (80%, 95% CI: 71 to 88%) was higher than that in adults (67%, CI: 60% to 74%). Oral fluid assays (OF) using spike protein and RBD antigens were also 99% specific and achieved reasonable but lower sensitivity in the target population (78%, 95% CI [68% to 86%] and 53%, 95% CI [43% to 64%], respectively). IMPORTANCE We report on the first large-scale assessment of the suitability of oral fluids for detection of SARS-CoV-2 antibody obtained from healthy children attending school. The sample type (gingiva-crevicular fluid, which is a transudate of blood but is not saliva) can be self collected. Although detection of antibodies in oral fluids is less sensitive than that in blood, our study suggests an optimal format for operational use. The laboratory methods we have developed can reliably measure antibodies in children, who are able to take their own samples. Our findings are of immediate practical relevance for use in large-scale seroprevalence studies designed to measure exposure to infection, as they typically require venipuncture. Overall, our data indicate that OF assays based on the detection of SARS-CoV-2 antibodies are a tool suitable for population-based seroepidemiology studies in children and highly acceptable in children and adults, as venipuncture is no longer necessary.

3.
Preprint | EuropePMC | ID: ppcovidwho-297070

ABSTRACT

Background: There are limited data on immune responses to heterologous COVID–19 immunisation schedules, especially following an extended ≥12–week interval between doses. Methods: SARS–CoV–2 infection–naïve and previously–infected adults receiving ChAd–BNT (ChAdOx1 nCoV–19, AstraZeneca followed by BNT162b2, Pfizer–BioNTech) or BNT–ChAd as part of the UK national immunisation programme provided blood samples at 30 days and 12 weeks after their second dose. Geometric mean concentrations (GMC) of anti–SARS–CoV–2 spike (S-antibody) and nucleoprotein (N-antibody) IgG antibodies and geometric mean ratios (GMR) were compared with a contemporaneous cohort receiving homologous ChAd–ChAd or BNT–BNT. Results: During March–October 2021, 75,827 individuals were identified as having received heterologous vaccination, 9,489 invited to participate, 1,836 responded (19.3%) and 656 were eligible. In previously–uninfected adults, S–antibody GMC at 30 days post–second dose were lowest for ChAd–ChAd (862 (95%CI, 694– 1069)) and significantly higher for ChAd–BNT (6233 (5522– 7035);GMR 6.29;(5.04– 7.85);p<0.001), BNT-ChAd (4776 (4066– 5610);GMR 4.55 (3.56– 5.81);p<0.001) and BNT–BNT (5377 (4596– 6289);GMR 5.66 (4.49– 7.15);p<0.001). By 12 weeks after dose two, S–antibody GMC had declined in all groups and remained significantly lower for ChAd–ChAd compared to ChAd–BNT (GMR 5.12 (3.79– 6.92);p<0.001), BNT–ChAd (GMR 4.1 (2.96– 5.69);p<0.001) and BNT–BNT (GMR 6.06 (4.32– 8.50);p<0.001). Previously infected adults had higher S–antibody GMC compared to infection–naïve adults at all time–points and with all vaccine schedules. Conclusions: These real–world findings demonstrate heterologous schedules with adenoviral–vector and mRNA vaccines are highly immunogenic and may be recommended after a serious adverse reaction to one vaccine product, or to increase programmatic flexibility where vaccine supplies are constrained.

4.
Preprint | EuropePMC | ID: ppcovidwho-296775

ABSTRACT

ABSTRACT Background The role of educational settings on SARS-CoV-2 infection and transmission remains controversial. We investigated SARS-CoV-2 infection, seroprevalence and seroconversions rates in secondary schools during the 2020/21 academic year, which included the emergence of the more transmissible Alpha and Delta variants, in England. Methods The UK Health Security Agency (UKHSA) initiated prospective surveillance in 18 urban English secondary schools. Participants had nasal swabs for SARS-CoV-2 RT-PCR and blood sampling for SARS-CoV-2 Nucleoprotein and Spike protein antibodies at the start (Round 1: September-October 2020) and end (Round 2: December 2021) of the autumn term, when schools reopened after national lockdown was imposed in January 2021 (Round 3: March-April) and end of the academic year (Round 4: May-July). Findings We enrolled 2,314 participants (1277 students, 1037 staff). In-school testing identified 31 PCR-positive participants (20 students, 11 staff). Another 247 confirmed cases (112 students, 135 staff) were identified after linkage with national surveillance data, giving an overall positivity rate of 12.0% (278/2313;staff [14.1%, 146/1037] vs students [10.3%, 132/1276;p=0.006). Nucleoprotein-antibody seroprevalence increased for students and staff between Rounds 1-3 but changed little in Round 4, when the Delta variant was the dominant circulating strain. Overall, Nucleoprotein-antibody seroconversion was 18.4% (137/744) in staff and 18.8% (146/778) in students, while Spike-antibody seroconversion was higher in staff (72.8% (525/721) than students (21.3%, 163/764) because of vaccination. Interpretation SARS-CoV-2 infection and transmission in secondary schools remained low when community infection rates were low because of national lockdown, even after the emergence of the Delta variant Funding DHSC

5.
Nat Commun ; 12(1): 7217, 2021 Dec 10.
Article in English | MEDLINE | ID: covidwho-1565716

ABSTRACT

The UK prioritised delivery of the first dose of BNT162b2 (Pfizer/BioNTech) and AZD1222 (AstraZeneca) vaccines by extending the interval between doses up to 12 weeks. In 750 participants aged 50-89 years, we here compare serological responses after BNT162b2 and AZD1222 vaccination with varying dose intervals, and evaluate these against real-world national vaccine effectiveness (VE) estimates against COVID-19 in England. We show that antibody levels 14-35 days after dose two are higher in BNT162b2 recipients with an extended vaccine interval (65-84 days) compared with those vaccinated with a standard (19-29 days) interval. Following the extended schedule, antibody levels were 6-fold higher at 14-35 days post dose 2 for BNT162b2 than AZD1222. For both vaccines, VE was higher across all age-groups from 14 days after dose two compared to one dose, but the magnitude varied with dose interval. Higher dose two VE was observed with >6 week interval between BNT162b2 doses compared to the standard schedule. Our findings suggest higher effectiveness against infection using an extended vaccine schedule. Given global vaccine constraints these results are relevant to policymakers.

7.
Preprint in English | EuropePMC | ID: ppcovidwho-292973

ABSTRACT

Importance: There are limited data on immune responses after COVID-19 vaccine boosters in individuals receiving primary immunisation with BNT162b2 (Pfizer-BioNTech) or AZD1222 (AstraZeneca) Objective: To assess SARS-CoV-2 antibody responses before and after booster vaccination with BNT162b2 in adults receiving two BNT162b2 or AZD1222 vaccine doses at least 6 months previously, as part of the United Kingdom national immunisation schedule Design: Prospective, cohort study Setting: London, England Participants: 750 immunocompetent adults aged ≥50 years Interventions: A single dose of BNT162b2 administered at least six months after primary immunisation with two doses of BNT162b2 given <30 days apart (BNT162b2-control) or ≥30 days apart (BNT162b2-extended) compared to AZD1222 given ≥30 days apart (AZD1222-extended) Main Outcome and Measures: SARS-CoV-2 spike protein antibody geometric mean titres (GMTs) before and 2-4 weeks after booster Results: Of 750 participants, 626 provided serum samples for up to 38 weeks after their second vaccine dose. Antibody GMTs peaked at 2-4 weeks after the second dose, before declining by 68% at 36-38 weeks after dose 2 for BNT162b2-control participants, 85% at 24-29 weeks for BNT162b2-extended participants and 78% at 24-29 weeks for AZD1222-extended participants. Antibody GMTs was highest in BNT162b2-extended participants (942 [95%CI, 797-1113]) than AZD1222-extended (183 [124-268]) participants at 24-29 weeks or BNT162b2-control participants at 36-38 weeks (208;95%CI, 150-289). At 2-4 weeks after booster, GMTs were significantly higher than after primary vaccination in all three groups: 18,104 (95%CI, 13,911-23,560;n=47) in BNT162b2-control (76.3-fold), 13,980 (11,902-16,421;n=118) in BNT162b2-extended (15.9-fold) and 10,799 (8,510-13,704;n=43) in AZD1222-extended (57.2-fold) participants. BNT162b2-control participants (median:262 days) had a longer interval between primary and booster doses than BNT162b2-extended or AZD1222-extended (both median:186 days) participants. Conclusions and Relevance: We observed rapid serological responses to boosting with BNT162b2, irrespective of vaccine type or schedule used for primary immunisation, with higher post-booster responses with longer interval between primary immunisation and boosting. Boosters will not only provide additional protection for those at highest risk of severe COVID-19 but also prevent infection and, therefore, interrupt transmission, thereby reducing infections rates in the population. Ongoing surveillance will be important for monitoring the duration of protection after the booster.

8.
J Infect ; 83(5): 573-580, 2021 11.
Article in English | MEDLINE | ID: covidwho-1527750

ABSTRACT

OBJECTIVES: We assessed SARS-CoV-2 infection, seroprevalence and seroconversion in students and staff when secondary schools reopened in March 2021. METHODS: We initiated SARS-CoV-2 surveillance in 18 secondary schools across six regions in September 2020. Participants provided nasal swabs for RT-PCR and blood samples for SARS-CoV-2 antibodies at the beginning (September 2020) and end (December 2020) of the autumn term and at the start of the spring term (March 2021). FINDINGS: In March 2021, 1895 participants (1100 students:795 staff) were tested; 5.6% (61/1094) students and 4.4% (35/792) staff had laboratory-confirmed SARS-CoV-2 infection from December 2020-March 2021. Nucleoprotein-antibody seroprevalence was 36.3% (370/1018) in students and 31.9% (245/769) in staff, while spike-antibody prevalence was 39.5% (402/1018) and 59.8% (459/769), respectively, similar to regional community seroprevalence. Between December 2020 and March 2021, 14.8% (97/656; 95%CI: 12.2-17.7) students and 10.0% (59/590; 95%CI: 7.7-12.7) staff seroconverted. Weekly seroconversion rates were similar from September to December 2020 (8.0/1000) and from December 2020 to March 2021 (7.9/1000; students: 9.3/1,000; staff: 6.3/1,000). INTERPRETATION: By March 2021, a third of secondary school students and staff had evidence of prior infection based on N-antibody seropositivity, and an additional third of staff had evidence of vaccine-induced immunity based on S-antibody seropositivity.

9.
Euro Surveill ; 26(12)2021 03.
Article in English | MEDLINE | ID: covidwho-1154193

ABSTRACT

Sera were collected from 185 adults aged ≥ 70 years in London to evaluate the immune response to COVID-19 vaccines. A single dose of Pfizer/BioNtech vaccine resulted in > 94% seropositivity after 3 weeks in naïve individuals using the Roche Spike antibody assay, while two doses produced very high spike antibody levels, significantly higher than convalescent sera from mild-to-moderate PCR-confirmed adult cases. Our findings support the United Kingdom's approach of prioritising the first dose and delaying the second dose of COVID-19 vaccine.


Subject(s)
Antibodies, Viral/blood , Antibody Formation , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Aged , Aged, 80 and over , Humans , London
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