Evaluation of Immunogenicity to Three Doses of the SARS-CoV-2 BNT162b2 mRNA Vaccine in Lung Transplant Patients

Guardiani, Mariasilvia; Zingaropoli, Maria Antonella; Dezza, Francesco Cogliati; Centofanti, Anastasia; Carillo, Carolina; Tortellini, Eeva; Dominelli, Federica; Napoli, Anna; Borgo, Cosmo Del; Gaeta, Aurelia; Venuta, Federico; Vullo, Vincenzo; Lichtner, Miriam; Ciardi, Maria Rosa; Mastroianni, Claudio Maria; Russo, Gianluca

doi:10.3390/vaccines10101642

Cited by 3 publications

(6 citation statements)

References 34 publications

(52 reference statements)

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“…T-cell stimulation with SARS-CoV-2 specific peptide libraries T-cell specific response was assessed using a multiparametric flow cytometry after overnight stimulation with SARS-CoV-2 peptide libraries on isolated peripheral blood mononuclear cells (PBMCs), as previously described (12,21,31). Pools of lyophilized peptides, consisting mainly of 15-mer sequences with 11 amino acids overlap, covering the immunodominant sequence domains of the Spike glycoprotein (S) (GenBank MN908947.3, Protein QHD43416.1) and the Nucleocapsid phosphoprotein (N) (GenBank MN908947.3, Protein QHD43423.2) of SARS-CoV-2 were purchased from Miltenyi Biotec.…”

Section: Sars-cov-2 Anti-n and Anti-s Antibodiesmentioning

confidence: 99%

Multiple sclerosis-disease modifying therapies affect humoral and T-cell response to mRNA COVID-19 vaccine

et al. 2022

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BackgroundThe mRNA vaccines help protect from COVID-19 severity, however multiple sclerosis (MS) disease modifying therapies (DMTs) might affect the development of humoral and T-cell specific response to vaccination.MethodsThe aim of the study was to evaluate humoral and specific T-cell response, as well as B-cell activation and survival factors, in people with MS (pwMS) under DMTs before (T0) and after two months (T1) from the third dose of vaccine, comparing the obtained findings to healthy donors (HD). All possible combinations of intracellular IFNγ, IL2 and TNFα T-cell production were evaluated, and T-cells were labelled “responding T-cells”, those cells that produced at least one of the three cytokines of interest, and “triple positive T-cells”, those cells that produced simultaneously all the three cytokines.ResultsThe cross-sectional evaluation showed no significant differences in anti-S antibody titers between pwMS and HD at both time-points. In pwMS, lower percentages of responding T-cells at T0 (CD4: p=0.0165; CD8: p=0.0022) and triple positive T-cells at both time-points compared to HD were observed (at T0, CD4: p=0.0007 and CD8: p=0.0703; at T1, CD4: p=0.0422 and CD8: p=0.0535). At T0, pwMS showed higher plasma levels of APRIL, BAFF and CD40L compared to HD (p<0.0001, p<0.0001 and p<0.0001, respectively) and at T1, plasma levels of BAFF were still higher in pwMS compared to HD (p=0.0022).According to DMTs, at both T0 and T1, lower anti-S antibody titers in the depleting/sequestering-out compared to the enriching-in pwMS subgroup were found (p=0.0410 and p=0.0047, respectively) as well as lower percentages of responding CD4+ T-cells (CD4: p=0.0394 and p=0.0004, respectively). Moreover, the depleting/sequestering-out subgroup showed higher percentages of IFNγ-IL2-TNFα+ T-cells at both time-points, compared to the enriching-in subgroup in which a more heterogeneous cytokine profile was observed (at T0 CD4: p=0.0187; at T0 and T1 CD8: p =0.0007 and p =0.0077, respectively).ConclusionIn pwMS, humoral and T-cell response to vaccination seems to be influenced by the different DMTs. pwMS under depleting/sequestering-out treatment can mount cellular responses even in the presence of a low positive humoral response, although the cellular response seems qualitatively inferior compared to HD. An understanding of T-cell quality dynamic is needed to determine the best vaccination strategy and in general the capability of immune response in pwMS under different DMT.

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Section: Sars-cov-2 Anti-n and Anti-s Antibodiesmentioning

confidence: 99%

Multiple sclerosis-disease modifying therapies affect humoral and T-cell response to mRNA COVID-19 vaccine

et al. 2022

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“…In our setting, an uneven T-cell subset distribution was observed, in which IFNγ-IL2-TNFα+ and IFNγ-IL2+TNFα--producing T-cells prevailed. Since the quality of T-cell response, characterized by a multifunctional profile, has been associated with higher protection in response to infections and vaccinations [ 6 , 7 , 8 , 36 , 37 ], the highly uneven subset distribution of T-cells found in our cohort might indicate a qualitatively inferior T-cell response to vaccination. However, after twelve months since the third dose of the SARS-CoV-2 mRNA-based vaccine, a dynamic change in the subset distribution was observed, in which a more heterogeneous distribution, like HD ones, was observed in SOT-Rs as well.…”

Section: Discussionmentioning

confidence: 99%

“…In this context, mRNA-based vaccines have become the mainstay for the pandemic response, due to their ability to induce robust and protective humoral and cellular responses against SARS-CoV-2 [ 4 , 5 ]. However, in immunocompromised subjects, low rates of anti-Spike (anti-S) antibody levels and moderate vaccine effectiveness have been observed [ 3 , 6 , 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

The Long-Term Immunogenicity of mRNABNT162b Third Vaccine Dose in Solid Organ Transplant Recipients

Zingaropoli,

Guardiani,

Dominelli

et al. 2024

Vaccines

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We investigated humoral and T-cell response to a SARS-CoV-2 mRNA vaccine in solid organ transplant recipients (SOT-Rs) and healthy donors (HDs) before (T0) and after two (T1) and twelve months (T2) since the third dose administration. SOT-Rs were stratified according to the transplanted organ and to the time elapsed since the transplant. In SOT-Rs, detectable levels of anti-S antibodies were observed in 44%, 81% and 88% at T0, T1 and T2, respectively. Conversely, anti-S antibody levels were detected in 100% of HD at all time points. Lower antibody titers were observed in SOT-Rs compared to HDs, even stratifying by transplanted organs and the time elapsed since transplant. Lower percentages of responding and polyfunctional T-cells were observed in SOT-Rs as well as in each subgroup of SOT-Rs compared to HDs. At both T0 and T1, in SOT-Rs, a predominance of one cytokine production shortly was observed. Conversely, at T2, a dynamic change in the T-cells subset distribution was observed, similar to what was observed in HDs. In SOT-Rs, the third dose increased the rate of seroconversion, although anti-S levels remained lower compared to HDs, and a qualitatively inferior T-cell response to vaccination was observed. Vaccine effectiveness in SOT-Rs is still suboptimal and might be improved by booster doses and prophylactic strategies.

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“…As previously described [ 33 , 34 ], T-cell specific response was assessed on isolated PBMC using multiparametric flow cytometry after overnight stimulation with SARS-CoV-2 peptide libraries. Pools of lyophilized peptides, covering the immunodominant sequence domains of the Spike glycoprotein (S) (GenBank MN908947.3, Protein QHD43416.1) and the Nucleocapsid phosphoprotein (N) (GenBank MN908947.3, Protein QHD43423.2) of SARS-CoV-2 were purchased from Milteny Biotec (Milteny Biotec, Germany).…”

Section: Methodsmentioning

confidence: 99%

“…Surface and intracellular staining of stimulated T-cells by flow cytometry were made following a previously published protocol from our group [ 34 ]. Briefly, for the surface staining PacificBlue-conjugated anti-CD45 to identify cells belonging to lymphoid and myeloid lines, APC-Cy7-conjugated anti-CD4 and APC-conjugated anti-CD8 and APC-Cy7-conjugated anti-CD4 to identify CD4+ and CD8+ T-cells, respectively, were used.…”

Section: Methodsmentioning

confidence: 99%

Quality of T-Cell Response to SARS-CoV-2 mRNA Vaccine in ART-Treated PLWH

Tortellini

Zingaropoli

Mancarella

et al. 2022

IJMS

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We investigated specific humoral and T-cell responses in people living with HIV (PLWH) before (T0), after two (T1) and after six months (T2) from the third dose of the BNT162b2 vaccine. Healthy donors (HD) were enrolled. The specific humoral response was present in most PLWH already after the second dose, but the third dose increased both the rate of response and its magnitude. Collectively, no significant differences were found in the percentage of responding T-cells between PLWH and HD. At T0, stratifying PLWH according to CD4 cell count, a lower percentage of responding T-cells in <200 cells/µL subgroup compared to >200 cells/µL one was observed. At T1, this parameter was comparable between the two subgroups, and the same result was found at T2. However, the pattern of co-expression of IFNγ, IL2 and TNFα in PLWH was characterized by a higher expression of TNFα, independently of CD4 cell count, indicating a persistent immunological signature despite successful ART. mRNA vaccination elicited a specific response in most PLWH, although the cellular one seems qualitatively inferior compared to HD. Therefore, an understanding of the T-cell quality dynamic is needed to determine the best vaccination strategy and, in general, the capability of immune response in ART-treated PLWH.

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Evaluation of Immunogenicity to Three Doses of the SARS-CoV-2 BNT162b2 mRNA Vaccine in Lung Transplant Patients

Cited by 3 publications

References 34 publications

Multiple sclerosis-disease modifying therapies affect humoral and T-cell response to mRNA COVID-19 vaccine

Multiple sclerosis-disease modifying therapies affect humoral and T-cell response to mRNA COVID-19 vaccine

The Long-Term Immunogenicity of mRNABNT162b Third Vaccine Dose in Solid Organ Transplant Recipients

Quality of T-Cell Response to SARS-CoV-2 mRNA Vaccine in ART-Treated PLWH

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