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Open accessPosted ContentDOI: 10.1101/2021.03.03.21251066

Age-dependent immune response to the Biontech/Pfizer BNT162b2 COVID-19 vaccination

05 Mar 2021-medRxiv (Cold Spring Harbor Laboratory Press)-
Abstract: BackgroundThe SARS-CoV-2 pandemic has led to the development of various vaccines. Real-life data on immune responses elicited in the most vulnerable group of vaccinees over 80 years old is still underrepresented despite the prioritization of the elderly in vaccination campaigns. MethodsWe conducted a cohort study with two age groups, young vaccinees below the age of 60 and elderly vaccinees over the age of 80, to compare their antibody responses to the first and second dose of the BNT162b2 COVID-19 vaccination. ResultsWhile the majority of participants in both groups produced specific IgG antibody titers against SARS-CoV-2 spike protein, titers were significantly lower in elderly participants. Although the increment of antibody levels after the second immunization was higher in elderly participants, the absolute mean titer of this group remained lower than the <60 group. After the second vaccination, 31.3 % of the elderly had no detectable neutralizing antibodies in contrast to the younger group, in which only 2.2% had no detectable neutralizing antibodies. ConclusionOur data suggests that lower frequencies of neutralizing antibodies after BNT162b2 vaccination in the elderly population may require earlier revaccination to ensure strong immunity and protection against infection.

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Topics: Vaccination (54%), Antibody titer (54%), Immunization (51%)
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23 results found


Open accessJournal ArticleDOI: 10.3390/DIAGNOSTICS11060941
25 May 2021-
Abstract: Although universal vaccination is one of the most important healthcare strategies for limiting SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) circulation and averting the huge number of hospitalizations and deaths due to coronavirus disease 2019 (COVID-19), significant inter-individual variability of COVID-19 vaccines’ efficacies has been described, mostly due to heterogeneous immune response in recipients. This opinion paper hence aims to discuss aspects related to the opportunity of monitoring anti-SARS-CoV-2 antibodies before and after COVID-19 vaccination, highlighting the pros and cons of this strategy. In summary, the advantages of anti-SARS-CoV-2 antibodies’ testing in recipients of COVID-19 vaccination encompass an assessment of baseline seroprevalence of SARS-CoV-2 infection in non-vaccinated individuals; early identification of low or non-responders to COVID-19 vaccination; and timely detection of faster decay of anti-SARS-CoV-2 antibody levels. In contrast, potential drawbacks to date include an unproven equivalence between anti-SARS-CoV-2 antibody titer, neutralizing activity, and vaccine efficiency; the lack of cost-effective analyses of different testing strategies; the enormous volume of blood drawings and increase of laboratory workload that would be needed to support universal anti-SARS-CoV-2 antibodies testing. A potential solution entails the identification of cohorts to be prioritized for testing, including those at higher risk of being infected by variants of concern, those at higher risk of unfavorable disease progression, and subjects in whom vaccine immunogenicity may be expectedly lower and/or shorter.

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Topics: Vaccination (56%)

11 Citations


Open accessPosted ContentDOI: 10.1101/2021.04.19.21255714
Paul Naaber1, Paul Naaber2, Liina Tserel1, Kadri Kangro2  +12 moreInstitutions (2)
27 Apr 2021-medRxiv
Abstract: Background. The mRNA vaccines for SARS-CoV2 have proven highly effective and are currently used to vaccinate all age groups against COVID-19. Despite their high efficacy in clinical trials, there is limited data on the impact of age, sex, and side effects on vaccine-induced immune responses. Methods. We here studied the development of SARS-CoV-2 Spike protein RBD domain antibodies after two doses of the Pfizer-BioNTech Comirnaty mRNA vaccine in 118 healthy volunteers and correlated their immune response with age, sex, and side effects reported after the vaccinations. Findings. Our findings show a robust immune response to the Spike proteins RBD region after the first and the second vaccination dose. However, we also saw a decline of antibody levels at 6 weeks versus 1 week after the second dose, suggesting a waning of the immune response over time. Regardless of this, the antibody levels at 6 weeks after the second dose remained significantly higher than before the vaccination, after the first dose, or in COVID-19 convalescent individuals. We found a decreased vaccination efficacy but fewer adverse events in older individuals, and that mRNA vaccination is less efficient in older males whereas the detrimental impact of age on vaccination outcome is abolished in females at 6 weeks after the second dose. Interpretation. The Pfizer-BioNTech Comirnaty mRNA vaccine induces a strong immune response after two doses of vaccination but older individuals develop fewer side effects and decreased antibody levels at 6 weeks. The waning of anti-viral antibodies in particular in older male individuals suggests that both age and male sex act as risk factors in the immune response to the SARS-CoV-2 mRNA vaccine. Funding. The study was supported by the Centre of Excellence in Translational Genomics (EXCEGEN), and the Estonian Research Council grant PRG377 and SYNLAB Estonia.

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Topics: Vaccination (56%)

10 Citations


Open accessPosted ContentDOI: 10.1101/2021.04.08.21255055
Monge S, Olmedo C, Alejos B, Lapena M1  +2 moreInstitutions (1)
10 Apr 2021-medRxiv
Abstract: Objectives To estimate indirect and total (direct plus indirect) effects of COVID-19 vaccination in residents in long-term care facilities (LTCF). Design Registries-based cohort study including all residents in LTCF ≥65 years offered vaccination between 27 December 2020 and 10 March 2021. Risk of SARS-CoV-2 infection following vaccination was compared with the risk in the same individuals in a period before vaccination. Risk in non-vaccinated was also compared to a period before the vaccination programme to estimate indirect protection. Standardized cumulative risk was computed adjusted by previous documented infection (before the start of follow-up) and daily-varying SARS-CoV-2 incidence and reproductive number. Participants 573,533 records of 299,209 individuals in the National vaccination registry were selected; 99.0% had ≥1 vaccine-dose, 99.8% was Pfizer/BioNTech (BNT162b2). Residents mean age was 85.9, 70.9% were females. A previous SARS-CoV-2 infection was found in around 25% and 13% of participants, respectively, at the time of vaccine offer and in the reference period. Main outcome measures Documented SARS-CoV-2 infection identified in the National COVID-19 laboratory registry. Results Total VE was 57.2% (95% Confidence Interval: 56.1%-58.3%), and was highest ≥28 days after the first vaccine-dose (proxy of ≥7 days after the second dose) and for individuals naive to SARS-CoV-2 [81.8% (81.0%-82.7%)] compared to those with previous infection [56.8% (47.1%-67.7%)]. Vaccination prevented up to 9.6 (9.3-9.9) cases per 10.000 vaccinated per day; 11.6 (11.3-11.9) if naive vs. 0.8 (0.5-1.0) if previous infection. Indirect protection in the non-vaccinated could only be estimated for naive individuals, at 81.4% (73.3%-90.3%) and up to 12.8 (9.4-16.2) infections prevented per 10.000 indirectly protected per day. Conclusions Our results confirm the effectiveness of mRNA vaccination in institutionalized elderly population, endorse the policy of universal vaccination in this setting, including in people with previous infection, and suggest that even non-vaccinated individuals benefit from indirect protection. Key messages COIVD-19 vaccination reduced the risk of documented SARS-CoV-2 infection in institutionalized elderly by 57.2% (56.1% to 58.3%), which increased to 81.2% (80.2% to 82%) for the fully vaccinated. In individuals naive to SARS-CoV-2 vaccination reduced the risk by up to 81.8% and averted up to 11.6 cases per 10,000 vaccinated persons per day. Those with previous infection also benefited from a risk reduction of 57%, which translated in less than 1 infection averted per 10,000 vaccinated persons per day. Non-vaccinated individuals living in facilities where the majority (residents and staff) had been vaccinated showed a risk reduction similar to those actually vaccinated.

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Topics: Vaccination (52%)

10 Citations


Open accessPosted ContentDOI: 10.1101/2021.05.14.21257248
17 May 2021-medRxiv
Abstract: The rapid spread of SARS-CoV-2 globally continues to impact humanity on a global scale with rising morbidity and mortality. Despite the development of multiple effective vaccines, new vaccines continue to be required to supply ongoing demand. We report Day 42 interim safety and immunogenicity data from a Phase 2, randomized, placebo-controlled trial in Adults aged 18+ immunized with a virus-like particle vaccine candidate produced in plants displaying SARS-CoV-2 spike glycoprotein (CoVLP) adjuvanted with AS03 (NCT04636697). This report focuses on presenting safety, tolerability and immunogenicity, as measured by neutralizing antibody (NAb) and cell mediated immunity (IFN-{gamma} and IL-4 ELISpot) responses, in Adults aged 18-64 (Adults) and Older Adults aged 65+ (Older Adults). CoVLP adjuvanted with AS03 was well-tolerated and adverse events (AE) were primarily mild or moderate and of transient duration. AEs in Older Adults were more limited than those observed in the Adult population. CoVLP with AS03 induced a significant humoral immune response in both age cohorts. CoVLP with AS03 induced a greater humoral response in Adults than Older Adults after a single dose but this effect was overcome with a second dose when both age cohorts responded with NAb titers that were [~]10-fold higher than those in a panel of sera from patients recovering from COVID-19. A single dose of CoVLP with AS03 induced a significant IFN-{gamma} response in both age cohorts; a second dose significantly boosted IFN-{gamma} and IL-4 responses in both age cohorts. Adults generated a stronger IFN-{gamma} and IL-4 cellular response than did Older Adults after one or two doses of AS03-adjuvanted CoVLP. Safety and immunogenicity from Adults with comorbidities as well as final safety and immunogenicity responses after 12 months will be reported upon availability.

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Topics: Immunogenicity (52%)

4 Citations


Open accessPosted ContentDOI: 10.1101/2021.05.25.21257797
Marit J. van Gils1, Hugo D.G. Willegen1, Elke Wynberg1, Alvin X. Han1  +24 moreInstitutions (3)
25 May 2021-medRxiv
Abstract: Background The urgent need for, but limited availability of, SARS-CoV-2 vaccines worldwide has led to widespread consideration of dose sparing strategies, particularly single vaccine dosing of individuals with prior SARS-CoV-2 infection. Methods We evaluated SARS-CoV-2 specific antibody responses following a single-dose of BNT162b2 (Pfizer-BioNTech) mRNA vaccine in 155 previously SARS-CoV-2-infected individuals participating in a population-based prospective cohort study of COVID-19 patients. Participants varied widely in age, comorbidities, COVID-19 severity and time since infection, ranging from 1 to 15 months. Serum antibody titers were determined at time of vaccination and one week after vaccination. Responses were compared to those in SARS-CoV-2-naive health care workers after two BNT162b2 mRNA vaccine doses. Results Within one week of vaccination, IgG antibody levels to virus spike and RBD proteins increased 27 to 29-fold and neutralizing antibody titers increased 12-fold, exceeding titers of fully vaccinated SARS-CoV-2-naive controls (95% credible interval (CrI): 0.56 to 0.67 v. control 95% CrI: −0.16 to −0.02). Pre-vaccination neutralizing antibody titers had the largest positive mean effect size on titers following vaccination (95% CrI (0.16 to 0.45)). COVID-19 severity, the presence of comorbidities and the time interval between infection and vaccination had no discernible impact on vaccine response. Conclusion A single dose of BNT162b2 mRNA vaccine up to 15 months after SARS-CoV-2 infection provides neutralizing titers exceeding two vaccine doses in previously uninfected individuals. These findings support wide implementation of a single-dose mRNA vaccine strategy after prior SARS-CoV-2 infection.

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Topics: Vaccination (61%), Neutralizing antibody (52%), Population (51%)

4 Citations


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39 results found


Open accessJournal ArticleDOI: 10.1056/NEJMOA2001017
Na Zhu1, Dingyu Zhang, Wenling Wang1, Xingwang Li2  +15 moreInstitutions (3)
Abstract: In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.).

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Topics: Coronavirus (57%), Betacoronavirus (56%)

15,285 Citations


Open accessJournal ArticleDOI: 10.1001/JAMA.2020.2648
Zunyou Wu1, Jennifer M. McGoogan1Institutions (1)
07 Apr 2020-JAMA
Abstract: Background: Hospitalised COVID-19 patients are frequently elderly subjects with co-morbidities receiving polypharmacy, all of which are known risk factors for d

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Topics: Outbreak (56%)

10,464 Citations


Open accessJournal ArticleDOI: 10.1056/NEJMOA2034577
Abstract: Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a world...

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4,222 Citations


Open accessJournal ArticleDOI: 10.1016/S0140-6736(20)32661-1
Merryn Voysey1, Clemens Sac.1, Shabir A. Madhi, Lily Yin Weckx2  +78 moreInstitutions (30)
09 Jan 2021-The Lancet
Abstract: Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials.

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1,792 Citations


Open accessJournal ArticleDOI: 10.1056/NEJMOA2022483
Abstract: Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and spread globally, prompting an international effort to accelerate development of a vacci...

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1,543 Citations


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