Biology subjects

Percivalle, E.

Publications and source records attributed to Percivalle, E..

5 recordsLinked to original sources

bioRxiv2021

Immunity to SARS-CoV-2 up to 15 months after infection

BackgroundInformation concerning the longevity of immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) following natural infection may have considerable implications for durability of immunity induced by vaccines. Here, we monitored the SARS-CoV-2 specific immune response in convalescent coronavirus disease-2019 (COVID-19) patients up to 15 months after symptoms onset. MethodsThe levels of anti-spike and anti-receptor binding domain antibodies and neutralizing activities were tested in a total of 188 samples from 136 convalescent patients who experience mild to critical COVID-19. Specific memory B and T cell responses were measured in 76 peripheral blood mononuclear cell samples collected from 54 patients. Twenty-three vaccinated individuals were included for comparison. FindingsFollowing a peak at day 15-28 post-infection, the IgG antibody response and plasma neutralizing titers gradually decreased over time but stabilized after 6 months. Plasma neutralizing activity against G614 was still detected in 87% of the patients at 6-15 months. Compared to G614, the median neutralizing titers against Beta, Gamma and Delta variants in plasma collected at early (15-103 days) and late (9-15 month) convalescence were 16- and 8-fold lower, respectively. SARS-CoV-2-specific memory B and T cells reached a peak at 3-6 months and persisted in the majority of patients up to 15 months although a significant decrease in specific T cells was observed between 6 and 15 months. ConclusionThe data suggest that antiviral specific immunity especially memory B cells in COVID-19 convalescent patients is long-lasting, but some variants of concern, including the fast-spreading Delta variant, may at least partially escape the neutralizing activity of plasma antibodies. FundingEU-ATAC consortium, the Italian Ministry of Health, the Swedish Research Council, SciLifeLab, and KAW.

immunology↗

bioRxiv2021

Bispecific antibody prevents SARS-CoV-2 escape and protects mice from disease

Neutralizing antibodies targeting the receptor binding domain (RBD) of the SARS-CoV-2 Spike (S) are among the most promising approaches against coronavirus disease 2019 (COVID-19)1,2. We developed a bispecific, IgG1-like molecule (CoV-X2) based on two antibodies derived from COVID-19 convalescent donors, C121 and C1353. CoV-X2 simultaneously binds two independent sites on the RBD and, unlike its parental antibodies, prevents detectable S binding to Angiotensin-Converting Enzyme 2 (ACE2), the virus cellular receptor. Furthermore, CoV-X2 neutralizes SARS-CoV-2 and its variants of concern, as well as the escape mutants generated by the parental monoclonals. In a novel animal model of SARS-CoV-2 infection with lung inflammation, CoV-X2 protects mice from disease and suppresses viral escape. Thus, simultaneous targeting of non-overlapping RBD epitopes by IgG-like bispecific antibodies is feasible and effective, combining into a single molecule the advantages of antibody cocktails.

immunology↗

bioRxiv2020

Neutrophil extracellular traps induce the epithelial-mesenchymal transition: implications in post-COVID-19 fibrosis

The release of neutrophil extracellular traps (NETs), a process termed NETosis, avoids pathogen spread but may cause tissue injury. NETs have been found in severe COVID-19 patients, but their role in disease development is still unknown. The aim of this study is to assess the capacity of NETs to drive epithelial-mesenchymal transition (EMT) of lung epithelial cells and to analyze the involvement of NETs in COVID-19. Neutrophils activated with PMA (PMA-Neu), a stimulus known to induce NETs formation, induce both EMT and cell death in the lung epithelial cell line, A549. Notably, NETs isolated from PMA-Neu induce EMT without cell damage. Bronchoalveolar lavage fluid of severe COVID-19 patients showed high concentration of NETs. Thus, we tested in an in vitro alveolar model the hypothesis that virus-induced NET may drive EMT. Co-culturing A549 at air-liquid interface with alveolar macrophages, neutrophils and SARS-CoV2, we demonstrated a significant induction of the EMT in A549 together with high concentration of NETs, IL8 and IL1{beta}, best-known inducers of NETosis. Lung tissues of COVID-19 deceased patients showed that epithelial cells are characterized by increased mesenchymal markers. These results show for the first time that NETosis plays a major role in triggering lung fibrosis in COVID-19 patients.

immunology↗

bioRxiv2020

Persistence of SARS-CoV-2 specific B- and T-cell responses in convalescent COVID-19 patients 6-8 months after the infection

BackgroundThe longevity of the immune response against SARS-CoV-2 is currently debated. We thus profiled the serum anti-SARS-CoV-2 antibody levels and virus specific memory B- and T-cell responses over time in convalescent COVID-19 patients. MethodsA cohort of COVID-19 patients from the Lombardy region in Italy who experienced mild to critical disease and Swedish volunteers with mild symptoms, were tested for the presence of elevated anti-spike and anti-receptor binding domain antibody levels over a period of eight months. In addition, specific memory B- and T-cell responses were tested in selected patient samples. ResultsAnti-SARS-CoV-2 antibodies were present in 85% samples collected within 4 weeks after onset of symptoms in COVID-19 patients. Levels of specific IgM or IgA antibodies declined after 1 month while levels of specific IgG antibodies remained stable up to 6 months after diagnosis. Anti-SARS-CoV-2 IgG antibodies were still present, though at a significantly lower level, in 80% samples collected at 6-8 months after symptom onset. SARS-CoV-2-specific memory B- and T-cell responses were developed in vast majority of the patients tested, regardless of disease severity, and remained detectable up to 6-8 months after infection. ConclusionsAlthough the serum levels of anti-SARS-CoV-2 IgG antibodies started to decline, virus-specific T and/or memory B cell responses increased with time and maintained during the study period (6-8 months after infection). FundingEuropean Unions Horizon 2020 research and innovation programme (ATAC), the Italian Ministry of Health, CIMED, the Swedish Research Council and the China Scholarship Council.

immunology↗

bioRxiv2020

Clinical And Analytical Performance Of An Automated Serological Test That Identifies S1/S2 Neutralizing IgG In Covid-19 Patients Semiquantitatively.

BACKGROUNDIn the Covid-19 pandemic, highly selective serological testing is essential to define exposure to SARS-CoV-2 virus. Many tests have been developed, yet with variable speed to first result, and of unknown quality, particularly when considering the prediction of neutralizing capacity. OBJECTIVES/METHODSThe LIAISON(R) SARS-CoV-2 S1/S2 IgG assay was designed to measure antibodies against the SARS-CoV-2 native S1/S2 proteins in a standardized automated chemiluminescent assay. Clinical and analytical performance of the test were validated in an observational study using residual samples (>1500) with positive or negative Covid-19 diagnosis. RESULTSThe LIAISON(R) SARS-CoV-2 S1/S2 IgG assay proved highly selective and specific, and offers semiquantitative measures of serum or plasma levels of anti-S1/S2 IgG with neutralizing activity. The diagnostic sensitivity was 91.3% and 95.7% at >5 or [≥]15 days from diagnosis respectively, and 100% when assessed against a neutralizing assay. The specificity ranged between 97% and 98.5%. The average imprecision of the assay was <5 % coefficient of variation. Assay performance at 2 different cut-offs was evaluated to optimize predictive values in settings with different % disease prevalence. CONCLUSIONS. The automated LIAISON(R) SARS-CoV-2 S1/S2 IgG assay brings efficient, sensitive, specific, and precise serological testing to the laboratory, with the capacity to test large amounts of samples per day: first results are available within 35 minutes with a throughput of 170 tests/hour. The test also provides a semiquantitative measure to identify samples with neutralizing antibodies, useful also for a large scale screening of convalescent plasma for safe therapeutic use. IMPORTANCEWith the worldwide advance of the COVID-19 pandemic, efficient, reliable and accessible diagnostic tools are needed to support public health officials and healthcare providers in their efforts to deliver optimal medical care, and articulate sound demographic policy. DiaSorin has developed an automated serology based assay for the measurement of IgG specific to SARS CoV-2 Spike protein, and tested its clinical performance in collaboration with Italian health care professionals who provided access to large numbers of samples from infected and non-infected individuals. The assay delivers excellent sensitivity and specificity, and is able to identify samples with high levels of neutralizing antibodies. This will provide guidance in assessing the true immune status of subjects, as well as meeting the pressing need to screen donors for high titer convalescent sera for subsequent therapeutic and prophylactic use.

immunology↗