Persistent B cell memory after SARS-CoV-2 vaccination is functional during breakthrough infections

Terreri, Sara; Mortari, Eva Piano; Vinci, M.; Russo, Cristina; Alteri, Claudia; Albano, Christian; Colavita, Francesca; Gramigna, Giulia; Agrati, Chiara; Linardos, Giulia; Coltella, Luana; Colagrossi, Luna; Deriu, Gloria; Atti, Marta Ciofi Degli; Rizzo, Caterina; Scarsella, Marco; Brugaletta, Rita; Camisa, Vincenzo; Santoro, Annapaola; Roscilli, Giuseppe; Pavoni, Emiliano; Muzi, Alessia; Magnavita, Nicola; Scutari, Rossana; Villani, Alberto; Raponi, Massimiliano; Locatelli, Franco; Perno, Carlo Federico; Zaffina, Salvatore; Carsetti, Rita

doi:10.1016/j.chom.2022.01.003

Cited by 81 publications

(86 citation statements)

References 41 publications

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“…SARS-CoV-2-specific B cells were evaluated by flow cytometry in all 11 samples for the expression of markers for memory B cells (CD27) and cell surface immunoglobulin isotypes, such as IgG, IgA, and IgM, at T2 and T3. Despite a very significant reduction of circulating anti-spike antibodies ( Figures 1A, B ), we found that the percentage of SARS-CoV-2-specific memory B cells detected at T2 in our vaccinated subjects is comparable to current data in literature on the non-infected vaccinated ( 23 ) and, interestingly, is also comparable to data on COVID-19 convalescent subjects ( 2 ). Indeed, as shown in Figure 2A , the percent of SARS-CoV-2-specific memory B cells had a median value of 0.49% (SEM=0.06%) at T2.…”

Section: Resultssupporting

confidence: 88%

Specific Anti-SARS-CoV-2 Humoral and Cellular Immune Responses After Booster Dose of BNT162b2 Pfizer-BioNTech mRNA-Based Vaccine: Integrated Study of Adaptive Immune System Components

et al. 2022

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), is modifying human activity all over the world with significant health and economic burden. The advent of the SARS-CoV-2 pandemic prompted the scientific community to learn the virus dynamics concerning transmissibility, epidemiology, and usefulness of vaccines in fighting emerging health hazards. Pieces of evidence suggest that the first and second doses of mRNA vaccines induce a significant antibody response in vaccinated subjects or patients who recovered from SARS-CoV-2 infection, demonstrating the importance of the previously formed memory. The aim of this work has been to investigate the effects of BNT162b2 Pfizer-BioNTech mRNA-based vaccine booster dose in a cohort of 11 uninfected immunocompetent (ICs), evaluating the humoral and cellular responses, with more carefulness on memory B and T cells. Our findings underscore the potential benefit of the third dose of mRNA vaccine on the lifespan of memory B and T cells, suggesting that booster doses could increase protection against SARS-CoV-2 infection.

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Section: Resultssupporting

confidence: 88%

Specific Anti-SARS-CoV-2 Humoral and Cellular Immune Responses After Booster Dose of BNT162b2 Pfizer-BioNTech mRNA-Based Vaccine: Integrated Study of Adaptive Immune System Components

et al. 2022

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“…In addition, we show that the booster dose increased peak antibody levels measured after the second dose in all study groups, which further argues for established B cell memory. In line with our data are other studies showing that memory B cells are stable for several months after primary vaccination and ready to respond after infection or booster vaccination and that booster doses can even broaden the neutralizing capacity also against other virus variants ( 35 – 37 ). Even though a reduced neutralizing activity of vaccine-induced antibodies against the Delta and Omicron variant has been observed in healthy individuals ( 38 , 39 ), the vaccine-induced T cells responded equally well to the new emerging variants according to a recent data ( 40 , 41 ) emphasizing the importance of timely boosters in patients with weakened vaccine responsiveness.…”

Section: Discussionsupporting

confidence: 92%

SARS-CoV-2-mRNA Booster Vaccination Reverses Non-Responsiveness and Early Antibody Waning in Immunocompromised Patients – A Phase Four Study Comparing Immune Responses in Patients With Solid Cancers, Multiple Myeloma and Inflammatory Bowel Disease

et al. 2022

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BackgroundIndividuals with secondary immunodeficiencies belong to the most vulnerable groups to succumb to COVID-19 and thus are prioritized for SARS-CoV-2 vaccination. However, knowledge about the persistence and anamnestic responses following SARS-CoV-2-mRNA vaccinations is limited in these patients.MethodsIn a prospective, open-label, phase four trial we analyzed S1-specific IgG, neutralizing antibodies and cytokine responses in previously non-infected patients with cancer or autoimmune disease during primary mRNA vaccination and up to one month after booster.Results263 patients with solid tumors (SOT, n=63), multiple myeloma (MM, n=70), inflammatory bowel diseases (IBD, n=130) and 66 controls were analyzed. One month after the two-dose primary vaccination the highest non-responder rate was associated with lower CD19+ B-cell counts and was found in MM patients (17%). S1-specific IgG levels correlated with IL-2 and IFN-γ responses in controls and IBD patients, but not in cancer patients. Six months after the second dose, 18% of patients with MM, 10% with SOT and 4% with IBD became seronegative; no one from the control group became negative. However, in IBD patients treated with TNF-α inhibitors, antibody levels declined more rapidly than in controls. Overall, vaccination with mRNA-1273 led to higher antibody levels than with BNT162b2. Importantly, booster vaccination increased antibody levels >8-fold in seroresponders and induced anamnestic responses even in those with undetectable pre-booster antibody levels. Nevertheless, in IBD patients with TNF-α inhibitors even after booster vaccination, antibody levels were lower than in untreated IBD patients and controls.ConclusionImmunomonitoring of vaccine-specific antibody and cellular responses seems advisable to identify vaccination failures and consequently establishing personalized vaccination schedules, including shorter booster intervals, and helps to improve vaccine effectiveness in all patients with secondary immunodeficiencies.Trial registrationEudraCT Number: 2021-000291-11

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“…There are reports describing breakthrough infections post-vaccination, likely due to reduced/waning antibody levels and timing post-vaccination [30–33]. The breakthrough infection that occurred in our cohort, was in an individual with high neutralizing antibody levels similar to other recent reports [34, 35]. These data suggest that while antibody levels may be broadly predictive of vaccine efficacy, they are not sufficient as a singular correlate of protection in all individuals.…”

Section: Discussionsupporting

confidence: 72%

Impact of prior infection on SARS-CoV-2 antibody responses in vaccinated long-term care facility staff

Gallichotte

Nehring

Stromberg

et al. 2022

Preprint

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SARS-CoV-2 emerged in 2019 and has resulted in millions of deaths worldwide. Certain populations are at higher risk for infection, especially staff and residents at long term care facilities (LTCF), due to the congregant living setting, and residents with many comorbidities. Prior to vaccine availability, these populations represented a large fraction of total COVID-19 cases and deaths in the U.S. Due to the high-risk setting and outbreak potential, staff and residents were among the first groups to be vaccinated. To define the impact of prior infection on response to vaccination, we measured antibody responses in a cohort of staff members at a LTCF, many of whom were previously infected by SARS-CoV-2. We found that neutralizing, receptor-binding-domain (RBD) and nucleoprotein (NP) binding antibody levels were significantly higher post-full vaccination course in individuals that were previously infected, and NP antibody levels could discriminate individuals with prior infection from vaccinated individuals. While an anticipated antibody titer increase was observed after vaccine booster dose in naïve individuals, boost response was not observed in individuals with previous COVID-19 infection. We observed a strong relationship between neutralizing antibodies and RBD-binding antibodies post-vaccination across all groups, suggesting RBD-binding antibodies may be used as a correlate of neutralization. One individual with high levels of neutralizing and binding antibodies experienced a breakthrough infection (prior to the introduction of Omicron), demonstrating that the presence of antibodies is not always sufficient for complete protection against infection. These results highlight that history of COVID-19 exposure significantly increases SARS-CoV-2 antibody responses following vaccination.ImportanceLong-term care facilities (LTCFs) have been disproportionately impacted by COVID-19, due to their communal nature, high-risk profile of residents and vulnerability to respiratory pathogens. In this study, we analyzed the role of prior natural immunity to SARS-CoV-2 on post-vaccination antibody responses. The LTCF in our cohort experienced a large outbreak with almost 40% of staff becoming infected. We found that individuals that were infected prior to vaccination, had higher levels of neutralizing and binding antibodies post-vaccination. Importantly, the second vaccine dose significantly boosted antibody levels in those that were immunologically naïve prior to vaccination, but not those that had prior immunity. Regardless of pre-vaccination immune status, levels of binding and neutralizing antibodies were highly correlated. The presence of NP-binding antibodies can be used to identify individuals that were previously infected when pre-vaccination immune status is not known. Our results reveal that vaccination antibody responses differ depending on prior natural immunity.

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Persistent B cell memory after SARS-CoV-2 vaccination is functional during breakthrough infections

Cited by 81 publications

References 41 publications

Specific Anti-SARS-CoV-2 Humoral and Cellular Immune Responses After Booster Dose of BNT162b2 Pfizer-BioNTech mRNA-Based Vaccine: Integrated Study of Adaptive Immune System Components

Specific Anti-SARS-CoV-2 Humoral and Cellular Immune Responses After Booster Dose of BNT162b2 Pfizer-BioNTech mRNA-Based Vaccine: Integrated Study of Adaptive Immune System Components

SARS-CoV-2-mRNA Booster Vaccination Reverses Non-Responsiveness and Early Antibody Waning in Immunocompromised Patients – A Phase Four Study Comparing Immune Responses in Patients With Solid Cancers, Multiple Myeloma and Inflammatory Bowel Disease

Impact of prior infection on SARS-CoV-2 antibody responses in vaccinated long-term care facility staff

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