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Picture of the Favourable Immune Profile Induced by Anti-SARS-CoV-2 Vaccination.

ABSTRACT: COVID-19 pandemic has hit people's health, economy, and society worldwide. Great confidence in returning to normality has been placed in the vaccination campaign. The knowledge of individual immune profiles and the time required to achieve immunological protection is crucial to choose the best vaccination strategy. We compared anti-S1 antibody levels produced over time by BNT162b2 and AZD1222 vaccines and evaluated the induction of antigen-specific T-cells. A total of 2569 anti-SARS-CoV-2 IgG determination on dried blood spot samples were carried out, firstly in a cohort of 1181 individuals at random time-points, and subsequently, in an independent cohort of 88 vaccinated subjects, up to the seventeenth week from the first dose administration. Spike-specific T-cells were analysed in seronegative subjects between the two doses. AZD1222 induced lower anti-S1 IgG levels as compared to BNT162b2. Moreover, 40% of AZD1222 vaccinated subjects and 3% of BNT162b2 individuals resulted in seronegative during all the time-points, between the two doses. All these subjects developed antigen-specific T cells, already after the first dose. These results suggest that this test represents an excellent tool for a wide sero-surveillance. Both vaccines induce a favourable immune profile guaranteeing efficacy against severe adverse effects of SARS-CoV-2 infection, already after the first dose administration.

SUBMITTER: Lanuti P

PROVIDER: S-EPMC8391252 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Picture of the Favourable Immune Profile Induced by Anti-SARS-CoV-2 Vaccination.

Lanuti Paola P Rossi Claudia C Cicalini Ilaria I Pierdomenico Laura L Damiani Verena V Semeraro Daniela D Verrocchio Sara S Del Boccio Piero P Evangelista Adelia A Sarra Annalina A Zucchelli Mirco M Bologna Giuseppina G Simeone Pasquale P Catitti Giulia G Di Marco Federica F Stefanetti Simone S Vespa Simone S Sinjari Bruna B Bucci Ines I De Laurenzi Vincenzo V Di Battista Tonio T Stuppia Liborio L Pieragostino Damiana D

Biomedicines 20210818 8

COVID-19 pandemic has hit people's health, economy, and society worldwide. Great confidence in returning to normality has been placed in the vaccination campaign. The knowledge of individual immune profiles and the time required to achieve immunological protection is crucial to choose the best vaccination strategy. We compared anti-S1 antibody levels produced over time by BNT162b2 and AZD1222 vaccines and evaluated the induction of antigen-specific T-cells. A total of 2569 anti-SARS-CoV-2 IgG de ...[more]

PMID: 34440239

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Project description:Constant efforts to prevent infections by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are actively carried out around the world. Several vaccines are currently approved for emergency use in the population, while ongoing studies continue to provide information on their safety and effectiveness. CoronaVac is an inactivated SARS-CoV-2 vaccine with a good safety and immunogenicity profile as seen in phase 1, 2, and 3 clinical trials around the world, with an effectiveness of 65.9% for symptomatic cases. Although vaccination reduces the risk of disease, infections can still occur during or after completion of the vaccination schedule (breakthrough cases). This report describes the clinical and immunological profile of vaccine breakthrough cases reported in a clinical trial in progress in Chile that is evaluating the safety, immunogenicity, and efficacy of two vaccination schedules of CoronaVac (clinicaltrials.gov NCT04651790). Out of the 2,263 fully vaccinated subjects, at end of June 2021, 45 have reported symptomatic SARS-CoV-2 infection 14 or more days after the second dose (1.99% of fully vaccinated subjects). Of the 45 breakthrough cases, 96% developed mild disease; one case developed a moderate disease; and one developed a severe disease and required mechanical ventilation. Both cases that developed moderate and severe disease were adults over 60 years old and presented comorbidities. The immune response before and after SARS-CoV-2 infection was analyzed in nine vaccine breakthrough cases, revealing that six of them exhibited circulating anti-S1-RBD IgG antibodies with neutralizing capacities after immunization, which showed a significant increase 2 and 4 weeks after symptoms onset. Two cases exhibited low circulating anti-S1-RBD IgG and almost non-existing neutralizing capacity after either vaccination or infection, although they developed a mild disease. An increase in the number of interferon-γ-secreting T cells specific for SARS-CoV-2 was detected 2 weeks after the second dose in seven cases and after symptoms onset. In conclusion, breakthrough cases were mostly mild and did not necessarily correlate with a lack of vaccine-induced immunity, suggesting that other factors, to be defined in future studies, could lead to symptomatic infection after vaccination with CoronaVac.

Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are capable of inducing combined humoral and cellular immunity. Which effect is more relevant for their potent protective effects is unclear, but isolated T cell responses without seroconversion in healthy household members of individuals with Coronavirus disease 19 (COVID-19) suggest that T cell responses effectively protect against clinical infection. Oncologic patients have an outsize risk of unfavorable outcomes after SARS-CoV-2 infection and therefore were prioritized when vaccines first became available, although the quality of their immune response to vaccination was expected to be suboptimal, as has been confirmed in subsequent studies. Inherently, patients with anti-CD19 chimeric antigen receptor (CAR) T cell therapy-mediated B cell aplasia would be incapable of generating humoral responses, so that assessment of the vaccine-induced cellular immunity is all the more important to gauge whether the vaccine can induce meaningful protection. A salient difference between T cell and humoral responses is the former's relative impassiveness to mutations of the antigen, which is more relevant than ever since the advent of the omicron variant. The objective of this study was to assess the immune cell composition and spike protein-specific T cell responses before and after the first and second doses of SARS-CoV-2 mRNA vaccine in a cohort of juvenile CD19 CAR T cell therapy recipients with enduring B cell aplasia. The prospective study included all patients age >12 years diagnosed with multiply relapsed B cell precursor acute lymphoblastic leukemia and treated with anti-CD19 CAR T cell (CAR-T19) therapy in our center. The primary endpoint was the detection of cell-mediated and humoral responses to vaccine (flow cytometry and anti-S immunoglobulin G, respectively). Secondary endpoints included the incidence of vaccine-related grade 3 or 4 adverse events, exacerbation of graft-versus-host disease (GVHD), relapse, and the influence of the vaccine on CAR T cells and lymphocyte subsets. Even though one-half of the patients exhibited subnormal lymphocyte counts and marginal CD4/CD8 ratios, after 2 vaccinations all showed brisk T-cell responsiveness to spike protein, predominantly in the CD4 compartment, which quantitatively was well within the range of healthy controls. No severe vaccine-related grade 3 or 4 adverse events, GVHD exacerbation, or relapse was observed in our cohort. We posit that SARS-CoV-2 mRNA vaccines induce meaningful cellular immunity in patients with isolated B cell deficiency due to CAR-T19 therapy.

Project description:BackgroundTo investigate the factors that have significant impact on the Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) infection and vaccination induced immune response in rheumatoid arthritis (RA).MethodsSerological response was measured by quantifying anti-SARS-CoV-2 specific antibodies, while the cell-mediated response was measured by a whole-blood test quantifying the interferon (IFN)-γ response to different SARS-CoV-2-specific domains.ResultsWe prospectively enrolled 109 RA patients and 43 healthy controls. The median time (IQR) between the confirmed infection or the last vaccination dose and the day when samples were taken ("sampling interval") was 3.67 (2.03, 5.50) months in the RA group. Anti-Spike (anti-S) specific antibodies were detected in 94% of RA patients. Among the investigated patient related variables, age (p<0.004), sampling interval (p<0.001), the brand of the vaccine (p<0.001) and targeted RA therapy (TNF-inhibitor, IL-6 inhibitor, anti-CD20 therapy) had significant effect on the anti-S levels. After covariate adjustment TNF-inhibitor therapy decreased the anti-S antibody concentrations by 80% (p<0.001). The same figures for IL-6 inhibitor and anti-CD20 therapy were 74% (p=0.049) and 97% (p=0.002), respectively. Compared to subjects who were infected but were not vaccinated, the RNA COVID-19 vaccines increased the anti-S antibody levels to 71.1 (mRNA-1273) and 36.0 (BNT162b2) fold (p<0.001). The corresponding figure for the ChAdOx1s vaccine is 18.1(p=0.037). Anti-CCP (anti-cyclic citrullinated peptides) positive patients had 6.28 times (p= 0.00165) higher anti-S levels, than the anti-CCP negative patients. Positive T-cell response was observed in 87% of the healthy volunteer group and in 52% of the RA patient group. Following vaccination or infection it declined significantly (p= 0.044) but more slowly than that of anti-S titer (6%/month versus 25%). Specific T-cell responses were decreased by 65% in patients treated with anti-CD20 therapy (p=0.055).ConclusionOur study showed that the SARS-CoV-2-specific antibody levels were substantially reduced in RA patients treated with TNF-α-inhibitors (N=51) and IL-6-inhibitor (N=15). In addition, anti-CD20 therapy (N=4) inhibited both SARS-CoV-2-induced humoral and cellular immune responses. Furthermore, the magnitude of humoral and cellular immune response was dependent on the age and decreased over time. The RNA vaccines and ChAdOx1s vaccine effectively increased the level of anti-S antibodies.

Dataset Information

Picture of the Favourable Immune Profile Induced by Anti-SARS-CoV-2 Vaccination.

Publications

Picture of the Favourable Immune Profile Induced by Anti-SARS-CoV-2 Vaccination.

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