T follicular helper cells in the humoral immune response to SARS-CoV-2 infection and vaccination

Koutsakos, Marios; Lee, Wen Shi; Wheatley, Adam K.; Kent, Stephen J.; Juno, Jennifer A

doi:10.1002/jlb.5mr0821-464r

Cited by 32 publications

(32 citation statements)

References 90 publications

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“…Using the same modelling approach as above, the initial delay for T cell recall was ∼4 days (Table S2). The peak levels (amongst available samples) of ASCs and S-specific cTFH cells were positively correlated with the peak binding and neutralizing antibodies, as well as with each other (Fig S3), consistent with data from primary infection and vaccination ( 17 ).…”

Section: Figuresupporting

confidence: 85%

“…Given the potential of T cells to contribute to the control of viral replication and the association of CD4 + T cell responses with the development of neutralizing antibodies ( 17 ), we assessed the recall of S-specific CD4 + and CD8 + T cells following vaccination of seropositive individuals. Using re-stimulation with recombinant S protein and an activation-induced marker (AIM) assay (Fig S1 and S2), an increase in both S-specific CD4 + memory T cells (CD4 + Tmem; CD45RA - CXCR5 - )(Fig 2A and B) and circulating CD4 + T follicular helper cells (cTFH; CD45RA - CXCR5 + ) was evident from day 5 onwards, peaking around day 9 and declining thereafter (Fig 2C and D).…”

Section: Figurementioning

confidence: 99%

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Dynamics of immune recall following SARS-CoV-2 vaccination or breakthrough infection

Koutsakos

Lee

Reynaldi

et al. 2021

Preprint

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Vaccination against SARS-CoV-2 results in protection from acquisition of infection as well as improved clinical outcomes even if infection occurs, likely reflecting a combination of residual vaccine-elicited immunity and the recall of immunological memory. Here, we define the early kinetics of spike-specific humoral and T cell immunity after vaccination of seropositive individuals, and after breakthrough infection in vaccinated individuals. Intensive and early longitudinal sampling reveals the timing and magnitude of recall, with the phenotypic activation of B cells preceding an increase in neutralizing antibody titres. In breakthrough infections, the delayed kinetics of humoral immune recall provides a mechanism for the lack of early control of viral replication but likely underpins accelerated viral clearance and the protective effects of vaccination against severe COVID-19.

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Section: Figuresupporting

confidence: 85%

Section: Figurementioning

confidence: 99%

Dynamics of immune recall following SARS-CoV-2 vaccination or breakthrough infection

Koutsakos

Lee

Reynaldi

et al. 2021

Preprint

Self Cite

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“…While this study was neither designed nor powered to assess the impact of these immunological findings on actual protection from COVID-19 reinfection, these observations provide a good explanation for the better protection from COVID-19 reinfection of boosted convalescents compared to dually vaccinated COVID-19 naïve individuals observed in large epidemiological studies [ 27 , 28 ]. According to current understanding, a longer, broader and more intense interaction of T-follicular helper cells in infected and subsequently boosted individuals is thought to underlie this phenomenon [ 29 , 30 ]. It will be interesting to see how a third vaccine dose may shape the immune response in COVID-19 naïves.…”

Section: Discussionmentioning

confidence: 99%

Humoral immunity in dually vaccinated SARS-CoV-2-naïve individuals and in booster-vaccinated COVID-19-convalescent subjects

et al. 2022

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Background The immune response to COVID-19-vaccination differs between naïve vaccinees and those who were previously infected with SARS-CoV-2. Longitudinal quantitative and qualitative serological differences in these two distinct immunological subgroups in response to vaccination are currently not well studied. Methods We investigate a cohort of SARS-CoV-2-naïve and COVID-19-convalescent individuals immediately after vaccination and 6 months later. We use different enzyme-linked immunosorbent assay (ELISA) variants and a surrogate virus neutralization test (sVNT) to measure IgG serum titers, IgA serum reactivity, IgG serum avidity and neutralization capacity by ACE2 receptor competition. Results Anti-receptor-binding domain (RBD) antibody titers decline over time in dually vaccinated COVID-19 naïves whereas titers in single dose vaccinated COVID-19 convalescents are higher and more durable. Similarly, antibody avidity is considerably higher among boosted COVID-19 convalescent subjects as compared to dually vaccinated COVID-19-naïve subjects. Furthermore, sera from boosted convalescents inhibited the binding of spike-protein to ACE2 more efficiently than sera from dually vaccinated COVID-19-naïve subjects. Conclusions Long-term humoral immunity differs substantially between dually vaccinated SARS-CoV-2-naïve and COVID-19-convalescent individuals. Booster vaccination after COVID-19 induces a more durable humoral immune response in terms of magnitude and quality as compared to two-dose vaccination in a SARS-CoV-2-naïve background.

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“… 8 The generation of adequate immune responses following COVID-19 vaccination requires a series of cellular interactions between B cells and T cells, in which CD4 + T cells play a pivotal role. 9 , 10 After immunization, virus-specific CD4 + T cells can differentiate into T follicular helper (Tfh) and Th1 cells. Tfh cells provide “help” signals to B cells, and the interaction of SARS-CoV-2-specific Tfh cells with B cells is critical in developing neutralization antibody responses and long-term humoral immunity.…”

Section: Introductionmentioning

confidence: 99%

“…Tfh cells provide “help” signals to B cells, and the interaction of SARS-CoV-2-specific Tfh cells with B cells is critical in developing neutralization antibody responses and long-term humoral immunity. 9 , 11 Th1 cells produce interferon γ and related cytokines to exert direct antiviral functions. 10 HIV infection leads to persistent depletion of CD4 + T cells.…”

Section: Introductionmentioning

confidence: 99%

Safety and Immunogenicity of Inactivated COVID-19 Vaccines Among People Living with HIV in China

Han¹,

Yu²,

Han³

et al. 2022

IDR

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Purpose Vaccination reduces the incidence of severe COVID-19 and death and effectively limits viral spread. Concerns have been raised about COVID-19 vaccine responses in the large population of HIV-infected patients. This study aims to explore the safety and immunogenicity of the inactivated COVID-19 vaccine in people living with HIV (PLWH). Patients and Methods All participants in this study already had their second dose of an inactivated COVID-19 vaccine at least 14 days earlier, without a history of SARS-CoV-2 infection. The primary safety outcomes were the incidence of adverse reactions and changes in CD4 + T-cell counts. SARS-CoV-2 IgG and neutralizing antibody responses to the D614G variant and delta variant were measured for immune response assessment. Results Forty-seven HIV-infected patients and 18 healthy donors (HDs) were enrolled in this study. Adverse reactions were mild or self-limiting and were reported in 19.1% of HIV-infected patients. Most PLWH developed antibody responses against the inactivated COVID-19 vaccine. The longitudinal analysis of antibody responses in PLWH (median interval between detection and complete vaccination, 59 days) showed that antibodies were maintained for at least three months, though their titers were reduced. However, the antibody-positive rates in PLWH were significantly lower than those in HDs. Additionally, compared to HDs (Geomean titers (GMT) of 165 for D614G and GMT of 72 for delta), the neutralizing antibody titers against the two variants in PLWH (GMT of 43 for D614G and GMT 13 for delta) were decreased significantly (p = 0.018 and p < 0.001, respectively). HIV-infected patients with CD4 + T-cell counts ≤350 cells/μL appeared to exhibit a poor antibody response to inactivated vaccination. Conclusion Inactivated COVID-19 vaccines appear to be efficacious in PLWH. However, antibody responses in HIV-infected patients are inferior to those in healthy individuals, especially PLWH with lower CD4 + T-cell counts.

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T follicular helper cells in the humoral immune response to SARS-CoV-2 infection and vaccination

Cited by 32 publications

References 90 publications

Dynamics of immune recall following SARS-CoV-2 vaccination or breakthrough infection

Dynamics of immune recall following SARS-CoV-2 vaccination or breakthrough infection

Humoral immunity in dually vaccinated SARS-CoV-2-naïve individuals and in booster-vaccinated COVID-19-convalescent subjects

Safety and Immunogenicity of Inactivated COVID-19 Vaccines Among People Living with HIV in China

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