Strong humoral immune responses against SARS-CoV-2 Spike after BNT162b2 mRNA vaccination with a 16-week interval between doses

Tauzin, Alexandra; Gong, Shang Yu; Beaudoin-Bussières, Guillaume; Vézina, Dani; Gasser, Romain; Nault, Lauriane; Marchitto, Lorie; Benlarbi, Mehdi; Chatterjee, Debashree; Nayrac, Manon; Laumaea, Annemarie; Prévost, Jérémie; Boutin, Marianne; Sannier, Gérémy; Nicolas, Alexandre; Bourassa, Catherine; Gendron‐Lepage, Gabrielle; Medjahed, Halima; Goyette, Guillaume; Bo, Yuxia; Perreault, Josée; Gokool, Laurie; Morrisseau, Chantal; Arlotto, Pascale; Bazin, Renée; Dubé, Mathieu; Serres, Gaston De; Brousseau, Nicholas; Richard, Jonathan; Rovito, Roberta; Côté, Marceline; Tremblay, Cécile; Marchetti, Giulia; Duerr, Ralf; Martel-Laferrière, Valérie; Kaufmann, Daniel E.; Finzi, Andrés

doi:10.1016/j.chom.2021.12.004

Cited by 91 publications

(114 citation statements)

References 75 publications

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“…Overall, our results show that the SARS-CoV-2 Spike is abundantly expressed at the surface of infected human pAECs. This confirms that SARS-CoV-2-infected cells represent a potential A limitation of our study is the relatively low number of individuals analyzed; however, we note that our results that used authentic SARS-CoV-2-infected pAECs are consistent with the findings of many widely used serological assays [5,27]. Overall, our results show that the SARS-CoV-2 Spike is abundantly expressed at the surface of infected human pAECs.…”

Section: Recognition Of Sars-cov-2 Infected Paecs Correlates With Spike Recognition At the Surface Of 293t Cells Pseudoviral Neutralizatisupporting

confidence: 87%

“…We then evaluated whether recognition of the Spike at the surface of the infected pAECs correlated with results generated via the serological assays normally used to study humoral responses in individuals who were infected/convalescent or vaccinated [5,27]. We observed that plasma recognition at the surface of infected (N+) cells significantly correlated with the binding of 293T cells expressing the full-length SARS-CoV-2 Spike (Figure 3A,D,G).…”

Section: Recognition Of Sars-cov-2 Infected Paecs Correlates With Spike Recognition At the Surface Of 293t Cells Pseudoviral Neutralizatimentioning

confidence: 92%

“…We then measured the recognition of the infected pAECs with plasma from eight convalescent individuals whose symptoms had begun 6 and 11 weeks previously (PSO) (Figure 2A-C,F) [5] and plasma from nine individuals who were SARS-CoV-2 naïve, obtained before vaccination (V0), at 3 weeks (V1) and 12 weeks (V2) after the first dose of the BNT162b2 mRNA vaccine, or at 3 weeks after the second dose (V3) (Figure 2D,E,G). The second dose was administered with an interval of 16 weeks between doses [27]. Representative flow cytometry contour plots of the specific recognition of (N+) pAECs infected with SARS-CoV-2 D614G (Figure 2B,D) or the Alpha variant (Figure 2C,E) are shown.…”

Section: Recognition Of Infected Human Primary Airway Epithelial Cells By Plasma From Individuals Who Were Previously Infected or Sars-comentioning

confidence: 99%

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SARS-CoV-2 Spike Expression at the Surface of Infected Primary Human Airway Epithelial Cells

Ding

Adam

Beaudoin-Bussières

et al. 2021

Viruses

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Different serological assays were rapidly generated to study humoral responses against the SARS-CoV-2 Spike glycoprotein. Due to the intrinsic difficulty of working with SARS-CoV-2 authentic virus, most serological assays use recombinant forms of the Spike glycoprotein or its receptor binding domain (RBD). Cell-based assays expressing different forms of the Spike, as well as pseudoviral assays, are also widely used. To evaluate whether these assays recapitulate findings generated when the Spike is expressed in its physiological context (at the surface of the infected primary cells), we developed an intracellular staining against the SARS-CoV-2 nucleocapsid (N) to distinguish infected from uninfected cells. Human airway epithelial cells (pAECs) were infected with authentic SARS-CoV-2 D614G or Alpha variants. We observed robust cell-surface expression of the SARS-CoV-2 Spike at the surface of the infected pAECs using the conformational-independent anti-S2 CV3-25 antibody. The infected cells were also readily recognized by plasma from convalescent and vaccinated individuals and correlated with several serological assays. This suggests that the antigenicity of the Spike present at the surface of the infected primary cells is maintained in serological assays involving expression of the native full-length Spike.

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Section: Recognition Of Sars-cov-2 Infected Paecs Correlates With Spike Recognition At the Surface Of 293t Cells Pseudoviral Neutralizatisupporting

confidence: 87%

Section: Recognition Of Sars-cov-2 Infected Paecs Correlates With Spike Recognition At the Surface Of 293t Cells Pseudoviral Neutralizatimentioning

confidence: 92%

Section: Recognition Of Infected Human Primary Airway Epithelial Cells By Plasma From Individuals Who Were Previously Infected or Sars-comentioning

confidence: 99%

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SARS-CoV-2 Spike Expression at the Surface of Infected Primary Human Airway Epithelial Cells

Ding

Adam

Beaudoin-Bussières

et al. 2021

Viruses

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“…(2021) ) found that longer dosing intervals (6–14 weeks) resulted in stronger immune responses than the standard regimen (3–4 weeks) for Comirnaty. Tauzin etal. (2021) also support that a longer (16 weeks) interval induced more robust immune responses than a shorter interval (4 weeks) for Cominarty.…”

Section: Rationale Behind Delaying the Second Dosementioning

confidence: 99%

Vaccination strategies and transmission of COVID-19: Evidence across advanced countries

Kim

Lee

2022

Journal of Health Economics

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Given limited supply of approved vaccines and constrained medical resources, design of a vaccination strategy to control a pandemic is an economic problem. We use time-series and panel methods with real-world country-level data to estimate effects on COVID-19 cases and deaths of two key elements of mass vaccination - time between doses and vaccine type. We find that new infections and deaths are both significantly negatively associated with the fraction of the population vaccinated with at least one dose. Conditional on first-dose coverage, an increased fraction with two doses appears to offer no further reductions in new cases and deaths. For vaccines from China, however, we find significant effects on both health outcomes only after two doses. Our results support a policy of extending the interval between first and second doses of vaccines developed in Europe and the US. As vaccination progresses, population mobility increases, which partially offsets the direct effects of vaccination. This suggests that non-pharmaceutical interventions remain important to contain transmission as vaccination is rolled out.

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“…Our data suggests that the response to the first dose is ongoing, with new T cell clones still being generated, at the time of administration of the second dose in the current dosing schedules (3/4-weeks for Pfizer/Moderna vaccines). Increasing the spacing between the first and second doses might allow the response to the first dose to play out, before further immune stimulation and give better protection, several studies now suggest this 45,46 . Data from Canada and Great Britain also seem to suggest that increasing the spacing might give better protection 47 .…”

Section: Discussionmentioning

confidence: 99%

The T cell receptor repertoire reflects the dynamics of the immune response to vaccination

Mohammed

Meadows²,

Hekmaty

et al. 2021

Preprint

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Early, high-resolution metrics are needed to ascertain the immune response to vaccinations. The T cell receptor (TCR), a heterodimer of one α and one β chain, is a promising target, with the complete TCR repertoire reflecting the T cells present in an individual. To this end, we developed Tseek, an unbiased and accurate method for profiling the TCR repertoire by sequencing the TCR α and β chains and developing a suite of tools for repertoire analysis. An added advantage is the ability to non-invasively analyze T cells in peripheral blood mononuclear cells (PBMCs). Tseek and the analytical suite were used to explore the T cell response to both the COVID-19 mRNA vaccine (n=9) and the seasonal inactivated Influenza vaccine (n=5) at several time points. Neutralizing antibody titers were also measured in the covid vaccine samples. The COVID-19 vaccine elicited a broad T cell response involving multiple expanded clones, whereas the Influenza vaccine elicited a narrower response involving fewer clones. Many distinct T cell clones responded at each time point, over a month, providing temporal details lacking in the antibody measurements, especially before the antibodies are detectable. In individuals recovered from a SARS-CoV-2 infection, the first vaccine dose elicited a robust T cell response, while the second dose elicited a comparatively weaker response, indicating a saturation of the response. The physical symptoms experienced by the recipients immediately following the vaccinations were not indicative of the TCR/antibody responses, while a weak TCR response seemed to presage a weak antibody response. We also found that the TCR repertoire acts as an individual fingerprint: donors of blood samples taken years apart could be identified solely based upon their TCR repertoire, hinting at other surprising uses the TCR repertoire may have. These results demonstrate the promise of TCR repertoire sequencing as an early and sensitive measure of the adaptive immune response to vaccination, which can help improve immunogen selection and optimize vaccine dosage and spacing between doses.

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Strong humoral immune responses against SARS-CoV-2 Spike after BNT162b2 mRNA vaccination with a 16-week interval between doses

Cited by 91 publications

References 75 publications

SARS-CoV-2 Spike Expression at the Surface of Infected Primary Human Airway Epithelial Cells

SARS-CoV-2 Spike Expression at the Surface of Infected Primary Human Airway Epithelial Cells

Vaccination strategies and transmission of COVID-19: Evidence across advanced countries

The T cell receptor repertoire reflects the dynamics of the immune response to vaccination

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