Highly Specific Memory B Cells Generation after the 2nd Dose of BNT162b2 Vaccine Compensate for the Decline of Serum Antibodies and Absence of Mucosal IgA

Mortari, Eva Piano; Russo, Cristina; Vinci, M.; Terreri, Sara; Salinas, Ane Fernandez; Piccioni, Livia; Alteri, Claudia; Colagrossi, Luna; Coltella, Luana; Ranno, Stefania; Linardos, Giulia; Agosta, Marilena; Albano, Christian; Agrati, Chiara; Castilletti, Concetta; Meschi, Silvia; Romania, Paolo; Roscilli, Giuseppe; Pavoni, Emiliano; Camisa, Vincenzo; Santoro, Annapaola; Brugaletta, Rita; Magnavita, Nicola; Ruggiero, Alessandra; Cotugno, Nicola; Amodio, Donato; Atti, Marta Luisa Cioffi Degli; Giorgio, Daniela; Russo, Nicoletta; Salvatori, Guglielmo; Corsetti, Tiziana; Locatelli, Franco; Perno, Carlo Federico; Zaffina, Salvatore; Carsetti, Rita

doi:10.3390/cells10102541

Cited by 66 publications

(99 citation statements)

References 43 publications

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“…While the spike-specific IgG titers in HC were slightly declining a month after the booster dose (Figure 2B), as recently reported [14][15][16][17], the antibodies elicited in MF patients were still increasing, thus showing a different kinetic of the secondary response, While the spike-specific IgG titers in HC were slightly declining a month after the booster dose (Figure 2B), as recently reported [14][15][16][17], the antibodies elicited in MF patients were still increasing, thus showing a different kinetic of the secondary response, with a slower development of the humoral response in MF patients. The antibody response dynamic observed in these subjects suggests a lower immunostimulating effect elicited by the first vaccine dose, as it was reported by two recent publications [8,10].…”

Section: Resultssupporting

confidence: 85%

The Slower Antibody Response in Myelofibrosis Patients after Two Doses of mRNA SARS-CoV-2 Vaccine Calls for a Third Dose

et al. 2021

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Immunization with mRNA SARS-CoV-2 vaccines has been highly recommended and prioritized in fragile subjects, including patients with myelofibrosis (MF). Available data on the vaccine immune response developed by MF patients and the impact of ruxolitinib treatment are still too fragmented to support an informed decision on a third dose for this category of subjects. Here, we show that 76% of MF patients develop spike-specific IgG after the second mRNA SARS-CoV-2 vaccine dose, but the response has a slower kinetics compared to healthy subjects, suggesting a reduced capability of their immune system to promptly react to vaccination. A reduced ACE2/RBD binding inhibition activity of spike-specific antibodies was also observed, especially in ruxolitinib-treated patients. Our results, showing slow kinetics of antibody responses in MF patients following vaccination with mRNA SARS-CoV-2 vaccines, support the need for a third vaccine dose.

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Section: Resultssupporting

confidence: 85%

The Slower Antibody Response in Myelofibrosis Patients after Two Doses of mRNA SARS-CoV-2 Vaccine Calls for a Third Dose

et al. 2021

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“…Recently, we showed that vaccination induces spike-specific (S+) ATMs in about one-third of patients in CVID [ 26 ], different from healthy subjects who respond by generating S+ MBCs ( Figure S2 ) [ 34 ].…”

Section: Resultsmentioning

confidence: 99%

B Cell Response Induced by SARS-CoV-2 Infection Is Boosted by the BNT162b2 Vaccine in Primary Antibody Deficiencies

Pulvirenti

Salinas

Milito

et al. 2021

Cells

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Background: Patients with primary antibody deficiencies are at risk in the current COVID-19 pandemic due to their impaired response to infection and vaccination. Specifically, patients with common variable immunodeficiency (CVID) generated poor spike-specific antibody and T cell responses after immunization. Methods: Thirty-four CVID convalescent patients after SARS-CoV-2 infection, 38 CVID patients immunized with two doses of the BNT162b2 vaccine, and 20 SARS-CoV-2 CVID convalescents later and immunized with BNT162b2 were analyzed for the anti-spike IgG production and the generation of spike-specific memory B cells and T cells. Results: Spike-specific IgG was induced more frequently after infection than after vaccination (82% vs. 34%). The antibody response was boosted in convalescents by vaccination. Although immunized patients generated atypical memory B cells possibly by extra-follicular or incomplete germinal center reactions, convalescents responded to infection by generating spike-specific memory B cells that were improved by the subsequent immunization. Poor spike-specific T cell responses were measured independently from the immunological challenge. Conclusions: SARS-CoV-2 infection primed a more efficient classical memory B cell response, whereas the BNT162b2 vaccine induced non-canonical B cell responses in CVID. Natural infection responses were boosted by subsequent immunization, suggesting the possibility to further stimulate the immune response by additional vaccine doses in CVID.

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“…Vaccine breakthrough infections may be because of deficient local preventive immunity due to absence of mucosal IgA. [22]…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, convalescent individuals that recovered from COVID-19 infection (also known as hybrid immunity) demonstrated the presence of specific IgA indicating that natural infection conferred mucosal immunity. [22,23 24]…”

Section: Discussionmentioning

confidence: 99%

Long-Term Persistence of IgG Antibodies in recovered COVID-19 individuals at 18 months and the impact of two-dose BNT162b2 (Pfizer-BioNTech) mRNA vaccination on the antibody response

Dehgani-Mobaraki¹,

Wang

Floridi³

et al. 2022

Preprint

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This era of emerging variants needs a thorough evaluation of data on the long-term efficacy of immune responses in vaccinated as well as recovered individuals, to understand the overall evolution of the pandemic. In this study, we aimed to assess the dynamics of IgG titers over 18 months in 34 patients from the Umbria region in Italy, who had a documented history of COVID-19 infection in March 2020, and then compared the impact of two-dose BNT162b2 (Pfizer-BioNTech) vaccination on the antibody titers of these patients with the ones who did not receive any dose of vaccine. This is the longest observation (March 2020-September 2021) for the presence of antibodies against SARS-CoV-2 in recovered individuals along with the impact of 2 dose-BNT162b2 vaccination on the titers. Fixed-effect regression models were used for statistical analysis which could be also used to predict future titer trends. At 18 months, 97% participants tested positive for anti-NCP hinting towards the persistence of infection-induced immunity even for the vaccinated individuals. Our study findings demonstrate that while double dose vaccination boosted the IgG titers in recovered individuals 161 times, this boost was relatively short-lived. The unvaccinated recovered individuals, in contrast, continued to show a steady decline but detectable antibody levels. Further studies are required to re-evaluate the timing and dose regimen of vaccines for an adequate immune response in recovered individuals.

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Highly Specific Memory B Cells Generation after the 2nd Dose of BNT162b2 Vaccine Compensate for the Decline of Serum Antibodies and Absence of Mucosal IgA

Cited by 66 publications

References 43 publications

The Slower Antibody Response in Myelofibrosis Patients after Two Doses of mRNA SARS-CoV-2 Vaccine Calls for a Third Dose

The Slower Antibody Response in Myelofibrosis Patients after Two Doses of mRNA SARS-CoV-2 Vaccine Calls for a Third Dose

B Cell Response Induced by SARS-CoV-2 Infection Is Boosted by the BNT162b2 Vaccine in Primary Antibody Deficiencies

Long-Term Persistence of IgG Antibodies in recovered COVID-19 individuals at 18 months and the impact of two-dose BNT162b2 (Pfizer-BioNTech) mRNA vaccination on the antibody response

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