A third dose of mRNA-1273 vaccine improves SARS-CoV-2 immunity in HCT recipients with low antibody response after 2 doses

Pettini, Elena; Ciabattini, Annalisa; Pastore, Gabiria; Polvere, Jacopo; Lucchesi, Simone; Fiorino, Fabio; Montagnani, Francesca; Bucalossi, Alessandro; Tozzi, Monica; Marotta, Giuseppe; Medaglini, Donata

doi:10.1182/bloodadvances.2021006599

Cited by 14 publications

(25 citation statements)

References 9 publications

(3 reference statements)

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“…The immune response kinetic observed in these subjects, showing a reduced capability of their immune system to rapidly react to vaccination, strongly suggested the need of booster vaccine dose ( 11 ), that was indeed recommended by the Centers for Disease Control and Prevention (CDC) for “fragile” subjects. On the matter we indeed recently demonstrated how the third dose of mRNA-1273 improved SARS-CoV-2 immunity in patients with hematologic malignancies treated with autologous and allogeneic hematopoietic cell transplantation, which exhibit a low response to the first cycle of vaccination ( 13 ).…”

Section: Introductionmentioning

confidence: 99%

The third dose of mRNA SARS-CoV-2 vaccines enhances the spike-specific antibody and memory B cell response in myelofibrosis patients

et al. 2022

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Vaccination against SARS-CoV-2 using mRNA-based vaccines has been highly recommended for fragile subjects, including myelofibrosis patients (MF). Available data on the immune responsiveness of MF patients to mRNA SARS-CoV-2 vaccination, and the impact of the therapy with the JAK inhibitor ruxolitinib, are still fragmented. Here, we profile the spike-specific IgG and memory B-cell response in MF patients, treated or not with ruxolitinib, after the second and the third dose of SARS-CoV-2 BNT162b2 (BioNTech) and mRNA-1273 (Moderna) vaccines. Plasma and peripheral blood mononuclear cells samples were collected before vaccination, post the second and the third doses and tested for spike-specific antibodies, ACE2/RBD antibody inhibition binding activity and spike-specific B cells. The third vaccine dose significantly increased the spike-specific IgG titers in both ruxolitinib-treated and untreated patients, and strongly enhanced the percentage of subjects with antibodies capable of in vitro blocking ACE2/RBD interaction, from 50% up to 80%. While a very low frequency of spike-specific B cells was measured in blood 7 days after the second vaccination dose, a strong and significant increase was elicited by the third dose administration, generating a B cell response similar to the one detected in healthy controls. Despite the overall positive impact of the third dose in MF patients, two patients that were under active concomitant immunosuppressive treatment at the time of vaccination, and a patient that received lymphodepleting therapies in the past, remained low responders. The third mRNA vaccine dose strongly increases the SARS-CoV-2 specific humoral and B cell responses in MF patients, promoting a reactivation of the immune response similar to the one observed in healthy controls.

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Section: Introductionmentioning

confidence: 99%

The third dose of mRNA SARS-CoV-2 vaccines enhances the spike-specific antibody and memory B cell response in myelofibrosis patients

et al. 2022

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“…The results of the antibody ELISA and neutralization assay indicate that, after the third vaccination, antibody concentrations and the distribution of titers remained similar in immunosuppressed individuals, whereas a significant increase was seen in healthy controls. Other studies have also previously shown that the humoral immune response to SARS-CoV-2 vaccination is reduced in 30-60% of HSCT patients [13,14,23]. Currently, there are very few studies on immune responses after third vaccination in HSCT patients.…”

Section: Discussionmentioning

confidence: 99%

“…HSCT was performed at a median of 4.1 years (range 0. [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] prior to blood sampling. The subgroup tested prior to the third vaccination contained 10 males and 14 females; the median age was 62 years (range 39-73).…”

Section: Volunteersmentioning

confidence: 99%

“…Studies have shown that a third vaccination is needed, particularly in vulnerable groups, to provide a protective effect against SARS-CoV-2 or to boost the existing weak immune response [10][11][12][13][14]. Currently, there are limited data on whether a third vaccination can boost specific immunity in immunocompromised patients after hematopoietic stemcell transplantation (HSCT).…”

Section: Introductionmentioning

confidence: 99%

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Cellular and Humoral Immunity after the Third Vaccination against SARS-CoV-2 in Hematopoietic Stem-Cell Transplant Recipients

et al. 2022

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Protecting vulnerable groups from severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection is mandatory. Immune responses after a third vaccination against SARS-CoV-2 are insufficiently studied in patients after hematopoietic stem-cell transplantation (HSCT). We analyzed immune responses before and after a third vaccination in HSCT patients and healthy controls. Cellular immunity was assessed using interferon-gamma (IFN-γ) and interleukin-2 (IL-2) ELISpots. Furthermore, this is the first report on neutralizing antibodies against 11 variants of SARS-CoV-2, analyzed by competitive fluorescence assay. Humoral immunity was also measured by neutralization tests assessing cytopathic effects and by ELISA. Neither HSCT patients nor healthy controls displayed significantly higher SARS-CoV-2-specific IFN-γ or IL-2 responses after the third vaccination. However, after the third vaccination, cellular responses were 2.6-fold higher for IFN-γ and 3.2-fold higher for IL-2 in healthy subjects compared with HSCT patients. After the third vaccination, neutralizing antibodies were significantly higher (p < 0.01) in healthy controls, but not in HSCT patients. Healthy controls vs. HSCT patients had 1.5-fold higher concentrations of neutralizing antibodies against variants and 1.2-fold higher antibody concentrations against wildtype. However, half of the HSCT patients exhibited neutralizing antibodies to variants of SARS-CoV-2, which increased only slightly after a third vaccination.

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“…Findings on other immunocompromised subjects suggest that a third dose can induce a strong immune response even in patients who did not develop immunity after the second dose (30,31). New studies are required to elucidate memory cell longevity and the effect of vaccine boosting.…”

Section: Discussionmentioning

confidence: 99%

B cell response six months after SARS-CoV-2 mRNA vaccination in people living with HIV under antiretroviral therapy

Polvere

Fabbiani²,

Pastore

et al. 2022

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Background SARS-CoV-2 mRNA vaccines have demonstrated high immunogenicity in healthy subjects and preliminary results for people living with HIV (PLWHIV) are promising too. We have previously reported the persistence of spike-specific circulating IgG and memory B cells in healthy adults up to six months after mRNA SARS-CoV-2 vaccination. Unfortunately, limited longitudinal data are available for PLWHIV and no evidence of persistent spike-specific B cells have been reported yet. Methods We investigated the humoral response and the persistence of spike-specific memory B cells up to six months after vaccination with two doses of mRNA vaccines in 84 PLWHIV under ART and compared them to healthy controls (HCs). Humoral response was analyzed with enzyme-linked immunosorbent assay and with an angiotensin-converting enzyme 2 (ACE2) and receptor binding domain (RBD) inhibition assay. PBMCs were analyzed with a cytofluorimetric approach for B cell phenotyping. Findings Spike-specific IgG peaked 1 month after second dose and persisted up to six months after vaccination with no significant differences compared to HCs. The stratification of patients according to CD4+ T cell count showed a significantly lower IgG response in case of CD4<350/μ, remarking the relevance of immune reconstitution. The ability of IgG of blocking the binding between ACE2 and RBD was detected in 58.4% of PLWHIV, compared to 86.2% in HCs. The amount of circulating spike-specific memory B cells detected in PLWHIV six months after vaccination was not significantly different from HCs, while there was prevalence of antigen-specific double negative (IgD-/CD27-) cells, compared to controls. Interpretation In conclusion, the majority of PLWHIV developed spike-specific humoral and B cell responses that persist for at least six months after SARS-CoV-2 mRNA vaccination. However, hints of HIV-dependent immune impairment were revealed by altered spike-specific B cell phenotypes and by reduced spike-specific humoral response in patients with low CD4+ T cell count (<350/μl).

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A third dose of mRNA-1273 vaccine improves SARS-CoV-2 immunity in HCT recipients with low antibody response after 2 doses

Cited by 14 publications

References 9 publications

The third dose of mRNA SARS-CoV-2 vaccines enhances the spike-specific antibody and memory B cell response in myelofibrosis patients

The third dose of mRNA SARS-CoV-2 vaccines enhances the spike-specific antibody and memory B cell response in myelofibrosis patients

Cellular and Humoral Immunity after the Third Vaccination against SARS-CoV-2 in Hematopoietic Stem-Cell Transplant Recipients

B cell response six months after SARS-CoV-2 mRNA vaccination in people living with HIV under antiretroviral therapy

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