ABSTRACT
BackgroundImmunizations among vulnerable population, including solid organ transplant recipients (SOT), present suboptimal responses at vaccination and over time. We investigated safety and immunogenicity of the BNT162B2 mRNA COVID-19 vaccine in 34 SOT young adults as compared to 36 healthy controls (HC). Methodsimmunogenicity was measured through the analysis of anti SARS-CoV2 IgG Antibodies and antigen specific CD4 T cells (CD40L+), detected by flow cytometry before vaccination, 21 days after priming (T21), 7 days after booster dose (T28) and 2-4 months after priming (T120). Baseline T and B cell immune phenotype was deeply investigated. The safety profile was investigated by close monitoring and self-reported diary. ResultsAnti-S and anti-Trimeric Ab responses were significantly lower in SOT vs HC at T21 (p<0.0001) and at T28 (p<0.0001). Ten out of 34 SOT (29%) at T28 and 3 out of 33 (9%) at T120 had undetectable SARS-CoV-2 IgG. The analysis of SARS-CoV-2 specific CD4 T cells showed lower CD40L expression after in vitro stimulation in SOT compared to HC. Lower frequencies of memory B cells were found in patients not responding to vaccination. Lack of seroconversion was higher in patients treated with mycophenolate (p=0.0005). The vaccination was safe and well tolerated. Only short-term adverse events, were reported and no hospitalization or graft rejection were observed after vaccinations. ConclusionsThese data show that SOT have a suboptimal immune response following mRNA vaccinations as compared to HC. Alternative strategies should be investigated to improve the immunization against SARS-CoV-2 in these patients.
ABSTRACT
BackgroundPatients with Primary Antibody Deficiencies (PAD) represent a potential at-risk group in the current COVID-19 pandemic. However, unexpectedly low cumulative incidence, low infection-fatality rate, and mild COVID-19 or asymptomatic SARS-CoV-2 infections were frequently reported in PAD. The discrepancy between clinical evidence and impaired antibody production requires in-depth studies on patients immune responses. MethodsForty-one patients with Common Variable Immune Deficiencies (CVID), 6 patients with X-linked Agammaglobulinemia (XLA), and 28 healthy age-matched controls (HD) were analyzed for anti-Spike and anti-RBD antibody production, generation of low and high affinity Spike-specific memory B-cells, Spike-specific T-cells before and one week after the second dose of BNT162b2 vaccine. ResultsHD produced antibodies, and generated memory B-cells with high affinity for Trimeric Spike. In CVID, the vaccine induced poor Spike-specific antibodies, and atypical B-cells with low affinity for Trimeric Spike, possibly by extra-follicular reactions or incomplete germinal center reactions. In HD, among Spike positive memory B-cells, we identified receptor-binding-domain-specific cells that were undetectable in CVID, indicating the incapability to generate this new specificity. Specific T-cell responses toward Spike-protein were evident in HD and defective in CVID. Due to the absence of B-cells, patients with XLA responded to immunization by specific T-cell responses only. ConclusionsWe present detailed data on early non-canonical immune responses in PAD to a vaccine against an antigen never encountered before by humans. From our data, we expect that after BNT162b2 immunization, XLA patients might be protected by specific T-cells, while CVID patients might not be protected by immunization.
ABSTRACT
Specific memory B cells and antibodies are reliable read-out of vaccine efficacy. We analyzed 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. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC="FIGDIR/small/21258284v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@1700325org.highwire.dtl.DTLVardef@deb172org.highwire.dtl.DTLVardef@53f056org.highwire.dtl.DTLVardef@c7a98d_HPS_FORMAT_FIGEXP M_FIG Graphical Abstract C_FIG
ABSTRACT
From February to April, 2020, Lombardy (Italy) was the area who worldwide registered the highest numbers of SARS-CoV-2 infection. By extensively analyzing 346 whole SARS-CoV-2 genomes, we demonstrated the simultaneous circulation in Lombardy of two major viral lineages, likely derived from multiple introductions, occurring since the second half of January. Seven single nucleotide polymorphisms (five of them non-synonymous) characterized the SARS-CoV-2 sequences, none of them affecting N-glycosylation sites. These two lineages, and the presence of two well defined clusters inside Lineage 1, revealed that a sustained community transmission was ongoing way before the first COVID-19 case found in Lombardy.
ABSTRACT
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.
