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1.
Cell Host Microbe ; 30(3): 400-408.e4, 2022 03 09.
Article in English | MEDLINE | ID: covidwho-1650182

ABSTRACT

Breakthrough SARS-CoV-2 infections in fully vaccinated individuals are considered a consequence of waning immunity. Serum antibodies represent the most measurable outcome of vaccine-induced B cell memory. When antibodies decline, memory B cells are expected to persist and perform their function, preventing clinical disease. We investigated whether BNT162b2 mRNA vaccine induces durable and functional B cell memory in vivo against SARS-CoV-2 3, 6, and 9 months after the second dose in a cohort of health care workers (HCWs). While we observed physiological decline of SARS-CoV-2-specific antibodies, memory B cells persist and increase until 9 months after immunization. HCWs with breakthrough infections had no signs of waning immunity. In 3-4 days, memory B cells responded to SARS-CoV-2 infection by producing high levels of specific antibodies in the serum and anti-Spike IgA in the saliva. Antibodies to the viral nucleoprotein were produced with the slow kinetics typical of the response to a novel antigen.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Vaccination , Vaccines, Synthetic
2.
SSRN; 2021.
Preprint in English | SSRN | ID: ppcovidwho-292059

ABSTRACT

Background: Breakthrough infections in fully vaccinated HCWs are considered a marker of waning immunity. Serum antibodies represent the most visible and measurable outcome of vaccine-induced B-cell memory. When antibodies decline, memory B cells are expected to persist and perform their function, thus preventing clinical disease. We investigated whether BNT162b2 mRNA vaccine induces durable and in vivo functional B-cell memory against SARS-CoV-2 3, 6 and 9 months after the second dose. Methods: We assessed the duration of SARS-CoV-2 vaccine-induced immunity by measuring specific antibodies and memory B cells 3, 6 and 9 months after vaccination. In fully vaccinated HCWs with breakthrough SARS-CoV-2 infections, we evaluated the humoral and mucosal response of vaccine-induced memory B cells. Findings: Whereas specific serum antibodies decline, anti-Spike memory B cells continue to increase until 9 months after the last vaccine dose. HCWs with breakthrough infections had no signs of waning immunity on the day of the first positive swab. In 3-4 days, memory B cells responded to SARS-CoV-2 infection by producing high levels of specific antibodies in the serum. In the saliva, anti-Spike IgA also rapidly increased in response to the infection. Antibodies to the viral nucleoprotein were produced with the slow kinetics typical of the response to a novel antigen. Interpretation: SARS-CoV-2 specific antibodies physiologically decline months after vaccination. By contrast, memory B cells persist and increase over time. Parenteral administered vaccines do not generate mucosal immunity and serum antibodies reach mucosal sites in small amounts by transudation. In HCWs with SARS-CoV-2 breakthrough infections, memory B cells react by rapidly differentiating into antibody-producing cells and generating IgA for protection of mucosal sites.

3.
Cells ; 10(10)2021 09 26.
Article in English | MEDLINE | ID: covidwho-1438527

ABSTRACT

Specific memory B cells and antibodies are a reliable read-out of vaccine efficacy. We analysed these biomarkers after one and two doses of BNT162b2 vaccine. The second dose significantly increases the level of highly specific memory B cells and antibodies. Two months after the second dose, specific antibody levels decline, but highly specific memory B cells continue to increase, thus predicting a sustained protection from COVID-19. We show that although mucosal IgA is not induced by the vaccination, memory B cells migrate in response to inflammation and secrete IgA at mucosal sites. We show that the first vaccine dose may lead to an insufficient number of highly specific memory B cells and low concentration of serum antibodies, thus leaving vaccinees without the immune robustness needed to ensure viral elimination and herd immunity. We also clarify that the reduction of serum antibodies does not diminish the force and duration of the immune protection induced by vaccination. The vaccine does not induce sterilizing immunity. Infection after vaccination may be caused by the lack of local preventive immunity because of the absence of mucosal IgA.


Subject(s)
Antibodies, Viral/immunology , B-Lymphocytes/cytology , COVID-19 Vaccines/therapeutic use , COVID-19/immunology , COVID-19/prevention & control , Immunoglobulin A/immunology , Immunologic Memory , Adult , Antibodies, Neutralizing/blood , Antigens, Viral/immunology , B-Lymphocytes/immunology , Cryopreservation , Female , Health Personnel , Healthy Volunteers , Hospitals, Pediatric , Humans , Immunoglobulin G , Immunoglobulin M/immunology , Lactation , Male , Middle Aged , Mucous Membrane/immunology , Patient Safety , SARS-CoV-2 , Vaccination
4.
Front Immunol ; 12: 690534, 2021.
Article in English | MEDLINE | ID: covidwho-1348488

ABSTRACT

High quality medical assistance and preventive strategies, including pursuing a healthy lifestyle, result in a progressively growing percentage of older people. The population and workforce is aging in all countries of the world. It is widely recognized that older individuals show an increased susceptibility to infections and a reduced response to vaccination suggesting that the aged immune system is less able to react and consequently protect the organism. The SARS-CoV-2 pandemic is dramatically showing us that the organism reacts to novel pathogens in an age-dependent manner. The decline of the immune system observed in aging remains unclear. We aimed to understand the role of B cells. We analyzed peripheral blood from children (4-18 years); young people (23-60 years) and elderly people (65-91 years) by flow cytometry. We also measured antibody secretion by ELISA following a T-independent stimulation. Here we show that the elderly have a significant reduction of CD27dull memory B cells, a population that bridges innate and adaptive immune functions. In older people, memory B cells are mostly high specialized antigen-selected CD27bright. Moreover, after in vitro stimulation with CpG, B cells from older individuals produced significantly fewer IgM and IgA antibodies compared to younger individuals. Aging is a complex process characterized by a functional decline in multiple physiological systems. The immune system of older people is well equipped to react to often encountered antigens but has a low ability to respond to new pathogens.


Subject(s)
Aging/immunology , B-Lymphocytes/immunology , COVID-19 , Immunologic Memory , Pandemics , SARS-CoV-2/immunology , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/epidemiology , COVID-19/immunology , Child , Child, Preschool , Cytokines/immunology , Female , Humans , Immunoglobulin A/immunology , Immunoglobulin M/immunology , Male , Middle Aged
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