Antibody responses to the BNT162b2 mRNA vaccine in individuals previously infected with SARS-CoV-2

Ebinger, Joseph; Fert-Bober, Justyna; Printsev, Ignat.; Wu, Min; Sun, Nancy; Prostko, John; Frias, Edwin C.; Stewart, James L.; Eyk, Jennifer E. Van; Braun, Jonathan; Cheng, Susan; Sobhani, Kimia

doi:10.1038/s41591-021-01325-6

Cited by 560 publications

(746 citation statements)

References 22 publications

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“…In our cohort, the T-cell responses increased significantly from baseline after the first dose of the vaccine (even as soon as 7 days after vaccination and before seroconversion), which was equivalent to responses in convalescent individuals. This is in contrast to reported antibody neutralization titers, which seem to require both doses to reach convalescent levels 36, 37 , unless the individual had prior SARS-CoV-2 exposure 48, 49 . The presence of a robust T-cell response comparable to convalescent patients after a single inoculation could suggest a similar level of SARS-CoV-2 protection and warrants further investigation as a possible measure to increase vaccine availability in resource-limited settings.…”

Section: Discussioncontrasting

confidence: 87%

SARS -CoV-2 T-cell immunity to variants of concern following vaccination

Gallagher

Leick

Larson

et al. 2021

Preprint

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Recently, two mRNA vaccines to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have become available, but there is also an emergence of SARS-CoV-2 variants with increased transmissibility and virulence. A major concern is whether the available vaccines will be equally effective against these variants. The vaccines are designed to induce an immune response against the SARS-CoV-2 spike protein, which is required for viral entry to host cells. Immunity to SARS-CoV-2 is often evaluated by antibody production, while less is known about the T-cell response. Here we developed, characterized, and implemented two standardized, functional assays to measure T-cell immunity to SARS-CoV-2 in uninfected, convalescent, and vaccinated individuals. We found that vaccinated individuals had robust T-cell responses to the wild type spike and nucleocapsid proteins, even more so than convalescent patients. We also found detectable but diminished T-cell responses to spike variants (B.1.1.7, B.1.351, and B.1.1.248) among vaccinated but otherwise healthy donors. Since decreases in antibody neutralization have also been observed with some variants, investigation into the T-cell response to these variants as an alternative means of viral control is imperative. Standardized measurements of T-cell responses to SARS-CoV-2 are feasible and can be easily adjusted to determine changes in response to variants.

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Section: Discussioncontrasting

confidence: 87%

SARS -CoV-2 T-cell immunity to variants of concern following vaccination

Gallagher

Leick

Larson

et al. 2021

Preprint

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“…Whether this persistent immunity may predispose dialysis patients to a similar triggering effect of a single vaccine dose as described for other populations, remains to be studied [ 9 ]. The demonstrated strong association between IgG spike levels and ACE2-receptor-binding-inhibition elicited by a single vaccine dose in dialysis patients was previously shown in patients with COVID-19 [ 10 ] and may confirm assay usability in dialysis patients.…”

Section: Discussionsupporting

confidence: 68%

Immunogenicity of a first dose of mRNA- or vector-based SARS-CoV-2 vaccination in dialysis patients: a multicenter prospective observational pilot study

Lesny¹,

Anderson

Cloherty

et al. 2021

J Nephrol

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Background Dialysis patients are at risk for lower SARS-CoV-2-vaccine immunogenicity than the normal population. We assessed immunogenicity to a first mRNA- or vector-based SARS-CoV-2-vaccination dose in dialysis patients. Methods In a multicenter observational pilot study, 2 weeks after a first vaccination (BNT162b2/Pfizer-BioNTech [Comirnaty] or ChAdOx1 nCoV-19/Oxford-Astra-Zeneca [Vaxzevria]), hemodialysis patients (N = 23), peritoneal dialysis patients (N = 4) and healthy staff (N = 14) were tested for SARS-CoV-2-spike IgG/IgM, Nucleocapsid-protein-IgG-antibodies and plasma ACE2-receptor-binding-inhibition capacity. Hemodialysis patients who had had prior COVID-19 infection (N = 18) served as controls. Both response to first SARS-CoV-2 vaccination and IgG spike-positivity following prior COVID-19 infection were defined as SARS-CoV-2 spike IgG levels ≥ 50 AU/mL. Results Vaccination responder rates were 17.4% (4/23) in hemodialysis patients, 100% (4/4) in peritoneal dialysis patients and 57.1% (8/14) in staff (HD vs. PD: p = 0.004, HD vs. staff: p = 0.027). Among hemodialysis patients, type of vaccine (Comirnaty N = 11, Vaxzevria N = 12, 2 responders each) did not appear to influence antibody levels (IgG spike: Comirnaty median 0.0 [1.–3. quartile 0.0–3.8] versus Vaxzevria 4.3 [1.6–20.1] AU/mL, p = 0.079). Of responders to the first dose of SARS-CoV-2 vaccination among hemodialysis patients (N = 4/23), median IgG spike levels and ACE2-receptor-binding-inhibition capacity were lower than that of IgG spike-positive hemodialysis patients with prior COVID-19 infection (13/18, 72.2%): IgG spike: median 222.0, 1.–3. quartile 104.1–721.9 versus median 3794.6, 1.–3. quartile 793.4–9357.9 AU/mL, p = 0.015; ACE2-receptor-binding-inhibition capacity: median 11.5%, 1.–3. quartile 5.0–27.3 versus median 74.8%, 1.–3. quartile 44.9–98.1, p = 0.002. Conclusions Two weeks after their first mRNA- or vector-based SARS-CoV-2 vaccination, hemodialysis patients demonstrated lower antibody-related response than peritoneal dialysis patients and healthy staff or unvaccinated hemodialysis patients following prior COVID-19 infection. Graphic abstract

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“…In contrast to healthy individuals in whom the second dose can probably be safely delayed, 20 the same is likely not true for most patients receiving hemodialysis. We do not know if anti-RBD IgG confers immunity against SARS-CoV-2 infection, but it is likely a good surrogate, as anti-RBD IgG correlates strongly with viral neutralization, 21 Fc-mediated efector functions and cellular responses. 22 Further, in our study, all survivors of COVID-19 mounted an anti-RBD response 4-16 weeks afer infection.…”

Section: Discussionmentioning

confidence: 99%

Short-term antibody response after 1 dose of BNT162b2 vaccine in patients receiving hemodialysis

Goupil

Benlarbi

Beaubien‐Souligny

et al. 2021

CMAJ

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BACKGROUND: Patients receiving in-R E S U L T S : O u r s t u d y i n c l u d e d after vaccination.Among those with centre hemodialysis are at high risk of 154 patients receiving hemodialysis previous SARS-CoV-2 infection, median exposure to SARS-CoV-2 and death if (135 without and 19 with previous SARS-anti-RBD IgG levels at 8 weeks in infected. One dose of the BNT162b2 SARS-CoV-2 infection), 40 controls (20 without patients receiving hemodialysis were CoV-2 vaccine is eficacious in the general and 20 with previous SARS-CoV-2 infec-similar to controls at 3 weeks (p = 0.3) population, but responses in patients tion) and convalescent plasma from and to convalescent plasma (p = 0.8). receiving hemodialysis are uncertain. 16 patients. Among those without previous SARS-CoV-2 infection, anti-RBD IgG INTERPRETATION: A single dose of METHODS: We obtained serial plasma was undetectable at 4 weeks in 75 of BNT162b2 vaccine failed to elicit a from patients receiving hemodialysis and 131 (57%, 95% confidence interval [CI] humoral immune response in most health care worker controls before and 47% to 65%) patients receiving hemodipatients receiving hemodialysis without after vaccination with 1 dose of the alysis, compared with 1 of 20 (5%, 95% previous SARS-CoV-2 infection, even BNT162b2 mRNA vaccine, as well as con-CI 1% to 23%) controls (p < 0.001). No after prolonged observation. In those valescent plasma from patients receiving patient with nondetectable levels at with previous SARS-CoV-2 infection, the hemodialysis who survived COVID-19. We 4 weeks developed anti-RBD IgG by antibody response was delayed. We measured anti-receptor binding domain 8 weeks. Results were similar in nonadvise that patients receiving hemodi-(RBD) immunoglobulin G (IgG) levels and immunosuppressed and younger indialysis be prioritized for a second stratified groups by evidence of previous viduals. Three patients receiving hemo-BNT162b2 dose at the recommended SARS-CoV-2 infection. dialysis developed severe COVID-19 3-week interval. Patients with end-stage kidney disease receiving in-this population. Some hemodialysis centres have thus prioricentre hemodialysis have been uniquely vulnerable dur-tized these patients for vaccination. ing the COVID-19 pandemic. For these patients, unlikeTo facilitate wider vaccine distribution during current shortfor most other people, self-isolation to avoid exposure to SARS-ages, 3 the National Advisory Committee on Immunization of Can-CoV-2 is impossible. Most patients receiving hemodialysis must ada has recommended delaying the second dose of the leave their homes 3 times weekly to receive their life-saving BNT162b2 vaccine from 3 to 16 weeks. 4 In a randomized contreatments, ofen in shared spaces for hours at a time. COVID-19 trolled trial (RCT), the clinical efficacy of the BNT162b2 was case fatality rates are 20%-30% for patients receiving hemodireported to be greater than 80% at 3 weeks afer the first dose. 5 alysis -10 times higher than in the general population. 1,2 However, no patients receiving hemodial...

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Antibody responses to the BNT162b2 mRNA vaccine in individuals previously infected with SARS-CoV-2

Cited by 560 publications

References 22 publications

SARS -CoV-2 T-cell immunity to variants of concern following vaccination

SARS -CoV-2 T-cell immunity to variants of concern following vaccination

Immunogenicity of a first dose of mRNA- or vector-based SARS-CoV-2 vaccination in dialysis patients: a multicenter prospective observational pilot study

Short-term antibody response after 1 dose of BNT162b2 vaccine in patients receiving hemodialysis

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