Spike-antibody waning after second dose of BNT162b2 or ChAdOx1

Shrotri, Madhumita; Navaratnam, Annalan M D; Nguyen, Vincent; Byrne, Thomas; Geismar, Cyril; Fragaszy, Ellen; Beale, Sarah; Fong, Wing Lam Erica; Patel, Parth; Kovar, Jana; Hayward, Andrew; Aldridge, Robert W

doi:10.1016/s0140-6736(21)01642-1

Cited by 380 publications

(349 citation statements)

References 19 publications

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“…Until recently, a fall in antibodies following vaccination with BNT162b2 has not been described in other studies with a more limited follow-up [ 2 , 6 ]. Our results are consistent with those from recent reports showing a continuous decline of anti-RBD antibodies within 10 weeks after vaccination in individuals who had received two doses of BNT162b2 [ 7 , 8 ]. This early decay of anti-RBD antibodies is similar to that observed in patients with mild SARS-CoV-2 infection within three months after the onset of symptoms [ 9 , 10 ].…”

Section: Discussionsupporting

confidence: 93%

Decline of antibody titres 3 months after two doses of BNT162b2 in non-immunocompromised adults

Erice

Varillas‐Delgado

Caballero

2022

Clinical Microbiology and Infection

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Objective To assess the antibody response in non-immunocompromised adults after two doses of BNT162b2. Methods Prospective, single-centre observational study in non-immunocompromised adults > 18 years of age who received two doses of BNT162b2. The study contemplates analyses of serum samples collected 1.5, 3, 6, 9 and 12 months after the second dose of BNT162b2; results of the 1.5-and 3-months’ time points are presented in this report. Antibodies against the receptor binding domain of the S1 subunit of the spike protein of SARS-CoV-2 (anti-RBD antibodies) were measured using a commercial quantitative immunoassay. A threshold of 4,160 AU/mL (corresponding to an ID 50 of 1:250) was used as surrogate marker for serum neutralizing activity. Results Of 273 hospital workers who received two doses of BNT162b2, 260/273 (95%) agreed to participate in the study; 2/260 (0.8%) were excluded due to immunocompromised conditions. At the time of this report, 230/258 (89%) subjects [mean age: 46.0 years (SD 11.4 years); 143/230 (62%) females; 87/230 (38%) males] had completed three months of follow-up after the second dose of BNT162b2. Thirty-six (16%) subjects (36/230) had documented mild SARS-CoV-2 infection prior to receiving the first dose of BNT162b2. Median [IQR] anti-RBD titres 1.5 months after vaccination were 9,356 [5,844 - 16,876] AU/mL; three months after vaccination, median anti-RBD titres had declined to 3,952 [2,190 - 8,561] AU/mL (p <0.001). Of 199/230 (86.5%) participants who had anti-RBD titres above 4,160 AU/mL 1.5 months after the second dose of BNT162b2, only 95/230 (41%) maintained anti-RBD titres above this level three months after vaccination (p < 0.001). Conclusions The decline of anti-RBD antibodies three months after the second dose of BNT162b2 is of concern because it raises the possibility of a short-lived humoral immunity after vaccination. Booster doses of BNT162b2 might be required to maintain high titers of anti-RBD antibodies over time.

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Section: Discussionsupporting

confidence: 93%

Decline of antibody titres 3 months after two doses of BNT162b2 in non-immunocompromised adults

Erice

Varillas‐Delgado

Caballero

2022

Clinical Microbiology and Infection

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“…Our overall finding of a differential humoral response according to vaccine type replicates data in healthy control cohorts [17]. However, we did not replicate this finding in people on anti-CD20 DMT, providing no rationale for recommending one vaccine type over another in those at particular risk of attenuated response.…”

Section: Discussioncontrasting

confidence: 40%

COVID-19 vaccine response in people with multiple sclerosis

Tallantyre

Vickaryous

Anderson

et al. 2021

Preprint

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Objective: To investigate the effect of disease modifying therapies on serological response to SARS-CoV2 vaccines in people with multiple sclerosis Methods: 473 people with multiple sclerosis from 5 centres provided one or more dried blood spot samples and a questionnaire about COVID-19 and vaccine history. Information about disease and drug history was extracted from their medical records. Dried blood spots were eluted and tested for antibodies to SARS-CoV2 receptor binding domain. Seropositivity was expressed according to validated cut-off indices. Antibody titers were partitioned into tertiles using data from people on no disease modifying therapy as a reference. We calculated the odds ratio of seroconversion (Univariate logistic regression) and compared quantitative vaccine response (Kruskal Wallis) following SARS-CoV2 vaccine according to disease modifying therapy. We used regression modelling to explore the effect of factors including vaccine timing, treatment duration, age, vaccine type and lymphocyte count on vaccine response. Results: Compared to no disease modifying therapy, the use of anti-CD20 monoclonal antibodies (odds ratio 0.03; 95% confidence interval 0.01-0.06, p<0.001) and fingolimod (odds ratio 0.41; 95% confidence interval 0.01-0.12) were associated with lower seroconversion following SARS-CoV2 vaccine. All other drug groups did not differ significantly from the untreated cohort. Both time since last anti-CD20 treatment and total time on treatment were significantly related with serological response to vaccination. Vaccine type significantly predicted seroconversion, but not in those on anti-CD20 medications. Interpretation: Some disease modifying therapies carry a risk of attenuated response to SARS-CoV2 vaccination in people with MS. We provide recommendations for the practical management of this patient group.

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“…We present data on 6030 and 2370 community-based adults in the UK with test-confirmed SARS-CoV-2 infection after their first or second COVID-19 vaccinations, respectively, with BNT162b2, ChAdOx1 nCoV-19, or mRNA-1273. Participants were included if they tested positive for SARS-CoV-2 at least 14 days after their first vaccination or at least 7 days after their second vaccination when immunity had developed 32 and infection was unlikely to be due to exposure around the time of vaccination (eg, when travelling to the vaccination centre).…”

Section: Discussionmentioning

confidence: 99%

Risk factors and disease profile of post-vaccination SARS-CoV-2 infection in UK users of the COVID Symptom Study app: a prospective, community-based, nested, case-control study

Antonelli

Penfold

Merino

et al. 2022

The Lancet Infectious Diseases

627

451

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Background COVID-19 vaccines show excellent efficacy in clinical trials and effectiveness in real-world data, but some people still become infected with SARS-CoV-2 after vaccination. This study aimed to identify risk factors for post-vaccination SARS-CoV-2 infection and describe the characteristics of post-vaccination illness. Methods This prospective, community-based, nested, case-control study used self-reported data (eg, on demographics, geographical location, health risk factors, and COVID-19 test results, symptoms, and vaccinations) from UK-based, adult (≥18 years) users of the COVID Symptom Study mobile phone app. For the risk factor analysis, cases had received a first or second dose of a COVID-19 vaccine between Dec 8, 2020, and July 4, 2021; had either a positive COVID-19 test at least 14 days after their first vaccination (but before their second; cases 1) or a positive test at least 7 days after their second vaccination (cases 2); and had no positive test before vaccination. Two control groups were selected (who also had not tested positive for SARS-CoV-2 before vaccination): users reporting a negative test at least 14 days after their first vaccination but before their second (controls 1) and users reporting a negative test at least 7 days after their second vaccination (controls 2). Controls 1 and controls 2 were matched (1:1) with cases 1 and cases 2, respectively, by the date of the post-vaccination test, health-care worker status, and sex. In the disease profile analysis, we sub-selected participants from cases 1 and cases 2 who had used the app for at least 14 consecutive days after testing positive for SARS-CoV-2 (cases 3 and cases 4, respectively). Controls 3 and controls 4 were unvaccinated participants reporting a positive SARS-CoV-2 test who had used the app for at least 14 consecutive days after the test, and were matched (1:1) with cases 3 and 4, respectively, by the date of the positive test, health-care worker status, sex, body-mass index (BMI), and age. We used univariate logistic regression models (adjusted for age, BMI, and sex) to analyse the associations between risk factors and post-vaccination infection, and the associations of individual symptoms, overall disease duration, and disease severity with vaccination status. Findings Between Dec 8, 2020, and July 4, 2021, 1 240 009 COVID Symptom Study app users reported a first vaccine dose, of whom 6030 (0·5%) subsequently tested positive for SARS-CoV-2 (cases 1), and 971 504 reported a second dose, of whom 2370 (0·2%) subsequently tested positive for SARS-CoV-2 (cases 2). In the risk factor analysis, frailty was associated with post-vaccination infection in older adults (≥60 years) after their first vaccine dose (odds ratio [OR] 1·93, 95% CI 1·50–2·48; p<0·0001), and individuals living in highly deprived areas had increased odds of post-vaccination infection following their first vaccine dose (OR 1·11, 95% CI 1·01–1·23; p=0·039). Individuals without obesity (...

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Spike-antibody waning after second dose of BNT162b2 or ChAdOx1

Cited by 380 publications

References 19 publications

Decline of antibody titres 3 months after two doses of BNT162b2 in non-immunocompromised adults

Decline of antibody titres 3 months after two doses of BNT162b2 in non-immunocompromised adults

COVID-19 vaccine response in people with multiple sclerosis

Risk factors and disease profile of post-vaccination SARS-CoV-2 infection in UK users of the COVID Symptom Study app: a prospective, community-based, nested, case-control study

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