Durability of immune responses to the BNT162b2 mRNA vaccine

Suthar, Mehul S.; Arunachalam, Prabhu S.; Hu, Mary Y.; Reis, Noah; Trisal, Meera; Raeber, Olivia; Chinthrajah, Sharon; Davis-Gardner, Meredith E.; Manning, Kelly; Mudvari, Prakriti; Boritz, Eli; Godbole, Sucheta; Henry, Amy R.; Douek, Daniel C.; Halfmann, Peter; Kawaoka, Yoshihiro; Boyd, Scott D.; Davis, Mark David McGregor; Zarnitsyna, Veronika I.; Nadeau, Kari; Pulendran, Bali

doi:10.1016/j.medj.2021.12.005

Cited by 39 publications

(50 citation statements)

References 9 publications

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“…Further different dynamics were observed for neutralizing antibody titers which were comparable at 3 and 6 months from full vaccination. This observation is in line with a recent publication [24] but in contrast with two other studies showing a persistent decay in functional antibodies between the first and second trimester from mRNA COVID-19 vaccine administration [20,25].…”

Section: Discussionsupporting

confidence: 92%

Differential Dynamics of SARS-CoV-2 Binding and Functional Antibodies upon BNT162b2 Vaccine: A 6-Month Follow-Up

Matusali

Sberna

Meschi

et al. 2022

Viruses

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To investigate the dynamic association among binding and functional antibodies in health-care-workers receiving two doses of BNT162b2 mRNA COVID-19-vaccine, SARS-CoV-2 anti-RBD IgG, anti-Trimeric-S IgG, and neutralizing antibodies (Nabs) were measured in serum samples collected at 2 weeks, 3 months, and 6 months from full vaccination. Despite the high correlation, results for anti-RBD and anti-Trimeric S IgG were numerically different even after recalculation to BAU/mL following WHO standards indications. Moreover, after a peak response at 2 weeks, anti-RBD IgG levels showed a 4.5 and 13 fold decrease at 3 and 6 months, respectively, while the anti-Trimeric S IgG presented a less pronounced decay of 2.8 and 4.7 fold. Further different dynamics were observed for Nabs titers, resulting comparable at 3 and 6 months from vaccination. We also demonstrated that at NAbs titers ≥40, the area under the receiver operating characteristic curve and the optimal cutoff point decreased with time from vaccination for both anti-RBD and anti-Trimeric S IgG. The mutating relation among the anti-RBD IgG, anti-Trimeric S IgG, and neutralizing antibodies are indicative of antibody maturation upon vaccination. The lack of standardized laboratory procedures is one factor interfering with the definition of a correlate of protection from COVID-19.

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Section: Discussionsupporting

confidence: 92%

Differential Dynamics of SARS-CoV-2 Binding and Functional Antibodies upon BNT162b2 Vaccine: A 6-Month Follow-Up

Matusali

Sberna

Meschi

et al. 2022

Viruses

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“…The short lifetime of these cells could explain the decline of IFN-γ responses over time observed in our study. However, this decline is consistent with the recent reports suggesting that spike-specific CD4+ T cells are downregulated at 3 and 6 months following vaccination ( 14 , 28 , 29 , 50 , 51 ) but contradict an interesting report suggesting that SARS-CoV-2–specific memory CD4+ T cells, based on the co-expression of CD200 and CD40L among CD45RA-, were relatively stable from 3 to 6 months after mRNA vaccination ( 52 ).…”

Section: Discussionsupporting

confidence: 90%

“…Data on cell-mediated immunity against SARS-CoV-2 are more subject to debate. Several reports suggested a decline in anti-spike specific CD4+ immune response after a few months ( 14 , 15 ) whereas, in recent reports, cell memory responses were observed to be relatively stable over 8 months following natural infection with SARS-CoV-2 ( 16 – 19 ). Clinical factors related to medical history and acute infection could be associated with variability in T-cell responses over time ( 19 ).…”

Section: Introductionmentioning

confidence: 97%

“…A few studies analysed the short-term cellular immune response following vaccination and showed that a maximum poly-specific cellular immune response against SARS-CoV-2 was elicited in a 3-week period immediately after BNT162b2 vaccination ( 27 , 28 ) and started to decrease over one month ( 28 ). The long-term specific T-cell response following vaccination is still little documented except in few studies reporting data on a small cohort of patients at 6 months post-vaccination ( 14 , 29 ). The technical complexity of T-cell response analysis limits studies to a small number of individuals by a few specialized laboratories.…”

Section: Introductionmentioning

confidence: 99%

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Decline of Humoral and Cellular Immune Responses Against SARS-CoV-2 6 Months After Full BNT162b2 Vaccination in Hospital Healthcare Workers

et al. 2022

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Clinical trials and real-world evidence on COVID-19 vaccines have shown their effectiveness against severe disease and death but the durability of protection remains unknown. We analysed the humoral and T-cell immune responses in 110 healthcare workers (HCWs) vaccinated according to the manufacturer’s recommended schedule of dose 2 three weeks after dose 1 from a prospective on-going cohort in early 2021, 3 and 6 months after full vaccination with the BNT162b2 mRNA vaccine. Anti-RBD IgG titres were lower in HCWs over 60 years old 3 months after the second dose (p=0.03) and declined in all the subjects between 3 and 6 months with a median percentage change of -58.5%, irrespective of age and baseline comorbidities. Specific T-cell response measured by IGRA declined over time by at least 42% (median) in 91 HCWs and increased by 33% (median) in 17 others. Six HCWs had a negative T-cell response at 6 months. Ongoing follow-up should provide correlates of long-term protection according to the different immune response profiles observed. COVIDIM study was registered under the number NCT04896788 on clinicaltrials.gov.

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“…Interestingly, IgG levels to the Alpha variant spike were markedly lower than those to the parent strain in the late HC group. These findings suggest that while mRNA vaccines initially stimulate robust humoral responses to variant viruses, these responses may be short-lived ( 15 – 17 ). Finally, microneutralization assay results indicated that the nAb response against the parent virus was maintained through 6 months in the late HC group, although the binding IgG response decreased, an observation also seen in a study of vaccinated health care workers followed for 6 months ( 16 ).…”

Section: Discussionmentioning

confidence: 96%

Adaptive immune responses in vaccinated patients with symptomatic SARS-CoV-2 Alpha infection

Park¹,

Shapiro²,

Sitaras³

et al. 2022

JCI Insight

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Benchmarks for protective immunity from infection or severe disease after SARS-CoV-2 vaccination are still being defined. Here we characterized virus neutralizing and ELISA antibody levels, cellular immune responses, and viral variants in 4 separate groups: Healthy control participants weeks (early) or months (late) following vaccination in comparison to symptomatic SARS-CoV-2 infections after partial or full mRNA vaccination. During the study time, most symptomatic breakthrough infections were caused by the SARS-CoV-2 Alpha variant. Neutralizing antibody levels in the healthy controls were sustained over time against the vaccine parent virus, but decreased against the Alpha variant, whereas IgG titers and T cell responses against the parent virus and Alpha variant declined over time in healthy controls. Both partially and fully vaccinated patients with symptomatic infections had lower virus neutralizing antibody levels against parent virus than the healthy controls, similar IgG antibody titers and similar virus-specific T cell responses measured by IFN-g. Compared to healthy controls, neutralization activity against the Alpha variant was lower in the partially vaccinated infected patients and tended toward lower in the fully vaccinated infected patients. In this cohort of breakthrough infections, parent virus neutralization was the superior predictor of breakthrough infections with the Alpha variant of SARS-CoV-2. Summary: Despite similar antibody titers and T-cell responses to vaccinated noninfected healthy controls, neutralizing capacity was reduced in those with breakthrough infection.

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Durability of immune responses to the BNT162b2 mRNA vaccine

Cited by 39 publications

References 9 publications

Differential Dynamics of SARS-CoV-2 Binding and Functional Antibodies upon BNT162b2 Vaccine: A 6-Month Follow-Up

Differential Dynamics of SARS-CoV-2 Binding and Functional Antibodies upon BNT162b2 Vaccine: A 6-Month Follow-Up

Decline of Humoral and Cellular Immune Responses Against SARS-CoV-2 6 Months After Full BNT162b2 Vaccination in Hospital Healthcare Workers

Adaptive immune responses in vaccinated patients with symptomatic SARS-CoV-2 Alpha infection

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