Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine

Payne, Rebecca; Longet, Stephanie; Austin, James; Skelly, Donal; Dejnirattisai, Wanwisa; Adele, Sandra; Meardon, Naomi; Faustini, Sian; Al-Taei, Saly; Moore, Shona C.; Tipton, Tom; Hering, Luisa M.; Angyal, Adrienn; Brown, Rachael; Nicols, Alexander R.; Gillson, Natalie; Dobson, Susan L; Amini, Ali; Supasa, Piyada; Cross, Andy; Bridges-Webb, Alice; Reyes, Laura Silva; Linder, Aline; Sandhar, Gurjinder; Kilby, J A; Tyerman, Jessica K.; Altmann, Thomas; Hornsby, Hailey; Whitham, Ruth H.; Phillips, Eloise; Malone, Tom; Hargreaves, Alexander; Shields, Adrian; Saei, Ayoub; Foulkes, Sarah; Stafford, Lizzie; Johnson, Síle A.; Wootton, Daniel G.; Conlon, Christopher P.; Jeffery, Katie; Matthews, Philippa C.; Frater, John; Deeks, Alexandra; Pollard, Andrew J.; Brown, Anthony; Rowland‐Jones, Sarah; Mongkolsapaya, Juthathip; Barnes, Eleanor; Hopkins, Susan; Hall, Victoria; Dold, Christina; Duncan, Christopher J A; Richter, Alex; Carroll, Miles W.; Screaton, Gavin; Silva, Thushan I. de; Turtle, Lance; Klenerman, Paul; Dunachie, Susanna

doi:10.1016/j.cell.2021.10.011

Cited by 272 publications

(268 citation statements)

References 42 publications

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“…is consistent with a previous study addressing a very large population which evidenced BNT162b2 vaccine effectiveness was of 57% after one dose and 97% after two doses (11). Other studies argue that extending the time of prime-boost interval enhances the recall response (22), which may be beneficial in the long term, notably by prolonging immune memory. However, in times of pandemic, with actual or risk of high infection incidence, frail populations would benefit from rapidly reaching effective immunity.…”

Section: Discussionsupporting

confidence: 91%

Longitudinal Analysis of Antibody Responses to the mRNA BNT162b2 Vaccine in Patients Undergoing Maintenance Hemodialysis: A 6-Month Follow-Up

et al. 2021

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Background: Patients on hemodialysis (HD) are at higher risk for COVID-19, overall are poor responders to vaccines, and were prioritized in the Portuguese vaccination campaign.Objective: This work aimed at evaluating in HD patients the immunogenicity of BTN162b2 after the two doses induction phase, the persistence of specific antibodies along time, and factors predicting these outcomes.Methods: We performed a prospective, 6-month long longitudinal cohort analysis of 156 HD patients scheduled to receive BTN162b2. ELISA quantified anti-spike IgG, IgM, and IgA levels in sera were collected every 3 weeks during the induction phase (t0 before vaccine; t1, d21 post first dose; and t2 d21 post second dose), and every 3–4 months during the waning phase (t3, d140, and t4, d180 post first dose). The age-matched control cohort was similarly analyzed from t0 to t2.Results: Upon exclusion of participants identified as previously exposed to SARS-CoV-2, seroconversion at t1 was lower in patients than controls (29 and 50%, respectively, p = 0.0014), while the second vaccine dose served as a boost in both cohorts (91 and 95% positivity, respectively, at t2, p = 0.2463). Lower response in patients than controls at t1 was a singularity of the participants ≤ 70 years (p = 2.01 × 10−05), associated with immunosuppressive therapies (p = 0.013), but not with lack of responsiveness to hepatitis B. Anti-spike IgG, IgM, and IgA levels decreased at t3, with IgG levels further waning at t4 and resulting in >30% seronegativity. Anti-spike IgG levels at t1 and t4 were correlated (ρ = 0.65, p < 2.2 × 10−16).Conclusions: While most HD patients seroconvert upon 2 doses of BNT162b2 vaccination, anti-spike antibodies levels wane over the following 4 months, leading to early seroreversion in a sizeable fraction of the patients. These findings warrant close monitoring of COVID-19 infection in vaccinated HD patients, and advocate for further studies following reinforced vaccination schedules.

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Section: Discussionsupporting

confidence: 91%

Longitudinal Analysis of Antibody Responses to the mRNA BNT162b2 Vaccine in Patients Undergoing Maintenance Hemodialysis: A 6-Month Follow-Up

et al. 2021

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“…Our followup study confirms that binding and neutralizing antibody activities induced by COVID-19 mRNA vaccines are significantly weaker in older adults at all time points following a twodose immunization series. In multivariable analyses, a higher number of chronic health conditions was also consistently independently associated with a weaker binding antibody response after two COVID-19 vaccine doses, while a longer interval between first and second vaccine doses was consistently Page 13 of 32 associated with higher binding antibody responses, as previously reported [34][35][36] . We also showed that binding antibody responses decline more rapidly over time in older adults, which can be attributed to a higher number of chronic health conditions in this group.…”

Section: Discussionsupporting

confidence: 76%

Older adults mount less durable humoral responses to two doses of COVID-19 mRNA vaccine, but strong initial responses to a third dose

Mwimanzi

Lapointe

Cheung

et al. 2022

Preprint

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Background. Two-dose mRNA vaccines reduce COVID-19 related hospitalization and mortality, but immune protection declines over time. As such, third vaccine doses are now recommended, particularly for older adults. We examined immune response durability up to 6 months after two vaccine doses, and immunogenicity after a third vaccine dose, in 151 adults ranging in age from 24 to 98 years. Methods. Specimens were collected from 81 healthcare workers (median age 41 years), 56 older adults (median 78 years) and 14 COVID-19 convalescent individuals (median 48 years), at one, three and six months following the second dose, and from 15 HCW, 28 older adults and 3 convalescent individuals at one month following a third dose. Binding antibodies to the SARS-CoV-2 spike receptor binding domain were quantified using a commercial immunoassay. Virus neutralizing activity was assessed using a live SARS-CoV-2 infection assay. Results. Compared to healthcare workers, older adults displayed ~0.3 log10 lower peak binding antibodies one month after the second dose (p<0.0001) and modestly faster rates of antibody decline thereafter (p=0.0067). A higher burden of chronic health conditions was independently associated with faster rates of antibody decline after correction for age, sociodemographic factors, and vaccine-related variables. Peak neutralizing activity was 4-fold lower in older adults one month after the second dose (p<0.0001) and became undetectable in the majority of individuals by six months. One month after a third dose, binding antibodies and neutralizing activities surpassed peak values achieved after two doses in both healthcare workers and older adults, and differences between these groups were no longer statistically significant. Compared to both naive groups, convalescent individuals displayed slower rates of binding antibody decline (p<0.006) and maintained higher neutralizing activity six months after the second dose. Conclusions. Immune responses to two-dose COVID-19 mRNA vaccines are overall weaker in older adults, and also decline more quickly over time, compared to younger adults. A third COVID-19 mRNA vaccine dose enhanced binding and neutralizing antibodies to levels higher than those observed after two vaccine doses, but the rate of decline of these responses should be monitored, particularly in older adults with a higher burden of chronic health conditions.

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“…The dosing interval seems to be an important factor that influences the seroconversion rates of NAb and S-RBD IgG since in the phase 1 clinical trials of CoronaVac, the 28-day-interval group showed higher seroconversion rates of NAb and S-RBD IgG than the 14-day-interval group ( 9 ). It was also reported that extension of the interval between vaccine doses for the BNT162b2 mRNA vaccine from the conventional 3-4 week regimen to 6-14 weeks resulted in higher NAb levels ( 16 ). This is consistent with our findings in the real-world settings that a longer interval between the first and second vaccination results in higher concentrations of S-RBD IgG 4 weeks after the second vaccination.…”

Section: Discussionmentioning

confidence: 99%

Characterization of SARS-CoV-2-Specific Humoral and Cellular Immune Responses Induced by Inactivated COVID-19 Vaccines in a Real-World Setting

et al. 2021

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While the immunogenicity of inactivated vaccines against coronavirus disease 2019 (COVID‐19) has been characterized in several well-conducted clinical trials, real-world evidence concerning immune responses against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) raised by such vaccines is currently missing. Here, we comprehensively characterized various parameters of SARS-CoV-2-specific cellular and humoral immune responses induced by inactivated COVID-19 vaccines in 126 individuals under real-world conditions. After two doses of vaccination, S-receptor binding domain IgG (S-RBD IgG) and neutralizing antibody (NAb) were detected in 87.06% (74/85) and 78.82% (67/85) of individuals, respectively. Female participants developed higher concentrations of S-RBD IgG and NAb compared to male vaccinees. Interestingly, a longer dosing interval between the first and second vaccination resulted in a better long-term SARS-CoV-2 S-RBD IgG response. The frequencies of CD4+ T cells that produce effector cytokines (IFN-γ, IL-2, and TNF-α) in response to stimulation with peptide pools corresponding to the SARS-CoV-2 spike (S), nucleocapsid (N) or membrane (M) protein were significantly higher in individuals received two doses of vaccine than those received one dose of vaccine and unvaccinated individuals. S, N, or M-specific CD4+ and CD8+ T cell responses were detectable in 95.83% (69/72) and 54.16% (39/72) of double-vaccinated individuals, respectively. The longitudinal analysis demonstrated that CD4+ T cell responses recognizing S, N, and M waned quickly after a single vaccine dose, but were boosted and became more sustained following a second dose. Overall, we provide a comprehensive characterization of immune responses induced by inactivated COVID-19 vaccines in real-world settings, suggesting that both humoral and cellular SARS-CoV-2-specific immunity are elicited in the majority of individuals after two doses of inactivated COVID-19 vaccines.

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Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine

Cited by 272 publications

References 42 publications

Longitudinal Analysis of Antibody Responses to the mRNA BNT162b2 Vaccine in Patients Undergoing Maintenance Hemodialysis: A 6-Month Follow-Up

Longitudinal Analysis of Antibody Responses to the mRNA BNT162b2 Vaccine in Patients Undergoing Maintenance Hemodialysis: A 6-Month Follow-Up

Older adults mount less durable humoral responses to two doses of COVID-19 mRNA vaccine, but strong initial responses to a third dose

Characterization of SARS-CoV-2-Specific Humoral and Cellular Immune Responses Induced by Inactivated COVID-19 Vaccines in a Real-World Setting

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