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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with a high rate of mortality in kidney transplant recipients (KTRs). Current vaccine strategies for KTRs seem to be unable to provide effective protection against coronavirus disease 2019 (COVID-19), and the occurrence of severe disease in some vaccinated KTRs suggested a lack of immunity. We initially analyzed the antibody response in a group of 32 kidney transplant recipients (KTRs) followed at the nephrology and dialysis unit of the Hospital Pio XI of Desio, ASST-Brianza, Italy. Thus, we studied the differences in antibody levels between subjects who contracted SARS-CoV-2 after the booster (8 individuals) and those who did not contract it (24 individuals). Furthermore, we verified if the antibody response was in any way associated with creatinine and eGFR levels. We observed a significant increase in the antibody response pre-booster compared to post-booster using both a Roche assay and DIAPRO assay. In the latter, through immunotyping, we highlight that the major contribution to this increase is specifically due to IgG S1 IgM S2. We observed a significant increase in IgA S1 and IgA NCP (p = 0.045, 0.02) in the subjects who contracted SARS-CoV-2. We did not find significant associations for the p-value corrected for false discovery rate (FDR) between the antibody response to all assays and creatinine levels. This observation allows us to confirm that patients require additional vaccine boosters due to their immunocompromised status and therapy in order to protect them from infections related to viral variants. This is in line with the data reported in the literature, and it could be worthwhile to deeply explore these phenomena to better understand the role of IgA S1 and IgA NCP antibodies in SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Background and Objective: Polypharmacy is common in older adults, particularly among those living in long-term care facilities. This condition represents a marker of clinical complexity and might directly affect the immunological response. However, there are limited data on the association of polypharmacy with vaccine immunogenicity. This study evaluated the immune response to anti-SARS-CoV-2 vaccines in older residents of long-term care facilities as a function of the number of medications used. Methods: In 478 long-term care facility residents participating in the GeroCovid Vax study, we assessed SARS-CoV-2 trimeric S IgG levels through chemiluminescent assays before the vaccination and after 2, 6, and 12 months. A booster dose was administered between 6- and 12-month assessments. Sociodemographic information and data on chronic diseases and medications were derived from medical records. Based on the number of daily medications, residents were classified into the no polypharmacy (zero to four medications), polypharmacy (five to nine medications), and hyperpolypharmacy (ten or more medications) groups. Results: In the sample (mean age 82.1 years, 69.2% female), 200 (41.8%) residents were taking five or fewer medications/day (no polypharmacy), 229 (47.9%) had polypharmacy, and 49 (10.3%) had hyperpolypharmacy. Using linear mixed models adjusted for potential confounders, we found that hyperpolypharmacy was associated with a steeper antibody decline after 6 months from the first vaccine dose administration (β = − 0.29, 95% confidence interval − 0.54, − 0.03, p = 0.03) than no polypharmacy, while no significant differences were observed at 12 months. Conclusions: The humoral immune response to SARS-CoV-2 vaccination of older residents showed only slight changes as a function of the number of medications taken. Although it seemed less durable among older residents with hyperpolypharmacy, the booster dose administration equalized such a difference. [ABSTRACT FROM AUTHOR]

This era of emerging variants needs a thorough evaluation of data on the long-term efficacy of immune responses in vaccinated as well as recovered individuals, to understand the overall evolution of the pandemic. In this study, we aimed to assess the dynamics of IgG response over 18 months in n = 36 patients from the Umbria region in Italy, who had a documented history of COVID-19 infection in March 2020, and then compared the impact of two-dose BNT162b2 (Pfizer-BioNTech) vaccination on the antibody responses of these patients with the ones who did not receive any dose of vaccine. This is the longest observation (March 2020–September 2021) for the presence of antibodies against SARS-CoV-2 in recovered individuals along with the impact of 2 dose-BNT162b2 vaccination on these responses. Fixed-effect regression models were used for statistical analysis which could be also used to predict future titer trends. At 18 months, 97% participants tested positive for anti-NCP hinting towards the persistence of infection-induced immunity even for the vaccinated individuals. Our study findings demonstrate that while double dose vaccination boosted the IgG levels in recovered individuals 161 times, this "boost" was relatively short-lived. The unvaccinated recovered individuals, in contrast, continued to show a steady decline but detectable antibody levels. Further studies are required to re-evaluate the timing and dose regimen of vaccines for an adequate immune response in recovered individuals. • This is the longest observation (March 2020–September 2021) for the presence of antibodies against SARS-CoV-2 in recovered individuals along with the impact of 2 dose-BNT162b2 vaccination on the titers. Fixed-effect regression models were used for statistical analysis which could be also used to predict future titer trends. At 18 months, 97% of participants tested positive for anti-NCP hinting towards the persistence of infection-induced immunity even for the vaccinated individuals. Our study findings demonstrate that while double dose vaccination boosted the IgG titers in recovered individuals 161 times, this "boost" was relatively short-lived. • The unvaccinated recovered individuals, in contrast, continued to show a steady decline but detectable antibody levels. • The major strengths of our study include the longest observation (March 2020–September 2021) for the presence of antibodies against SARS-CoV-2 in recovered individuals along with the impact of 2 dose-BNT162b2 vaccination on the titers. Secondly, fixed-effect regression models were used for statistical analysis that diminishes the impact of confounding by (unmeasured) fixed/time-invariant factors. These modeling results could also be used to predict future titer trends. Thirdly, since the immunoassay to detect anti-NCP was reintroduced at 18 months, even the vaccinated individuals could be analyzed for the persistence of infection-induced immunity not generated by mRNA spike-based vaccination. [ABSTRACT FROM AUTHOR]

Long-term care facilities (LTCFs) were severely affected by COVID-19, in particular in Northern Italy. We aimed to assess antibody responses among residents and healthcare workers (HCWs) of 13 LTCFs through serum samples collected at three time points: prior to, two weeks, and 9 months after receiving Pfizer/BNT162b2 SARS-CoV-2 mRNA vaccine (respectively t0, t1, and t2). IgG antibodies targeted towards the S1 domain of the spike protein were measured, and results were expressed in binding antibody units (BAU/mL). Friedman's average rank test was performed to compare antibody titres between the three time points. Two logistic regression models were built to identify independent predictors of (1) developing and (2) maintaining a significant antibody response to vaccination, using a previously identified threshold. In total, 534 subjects were enrolled (371 HCWs and 163 residents). The antibody titres at t1 were the highest; at t2, the IgG titres significantly decreased, remaining however 10 times higher compared to titres at t0. Previous infection was the only significant predictor of developing and maintaining a response over threshold in both models. Results of this study provided further insights on the humoral response elicited by vaccination, and on host factors determining variations in its magnitude and kinetics. [ABSTRACT FROM AUTHOR]

We evaluated SARS-CoV-2 antibody response in voluntary blood donors in Italy at different timepoints. Immediately after lockdown easing, 908/25,657 donors (3.5%) had low IgG titers against nucleocapsid. In the next 2 years, titers increased despite few COVID-19 symptoms. On multivariate analysis, allergic rhinitis was associated with reduced risk for symptomatic COVID-19. [ABSTRACT FROM AUTHOR]

Background: Nursing home (NH) residents suffered the greatest impact of the COVID-19 pandemic. Limited data are available on vaccine-induced immunity and on the protection ensured by a prior infection in this population. Aims: The present study aims to monitor antibody levels and their persistence over a 6-month period in NH residents according to the history of prior SARS-CoV-2 infection. Methods: We measured anti-trimeric Spike IgG antibody levels in a sample of 395 residents from 25 NHs in 6 Italian Regions at study enrolment (prior to the first dose of vaccine, T0) and then after 2 (T1) and 6 months (T2) following the first vaccine dose. All participants received mRNA vaccines (BNT162b2 or mRNA-1273). Analyses were performed using log-transformed values of antibody concentrations and geometric means (GM) were calculated. Results: Superior humoral immunity was induced in NH residents with previous SARS-CoV-2 infection. (T0: GM 186.6 vs. 6.1 BAU/ml, p < 0.001; T1: GM 5264.1 vs. 944.4 BAU/ml, p < 0.001; T2: GM 1473.6 vs. 128.7 BAU/ml, p < 0.001). Residents with prior SARS-CoV-2 infection receiving two vaccine doses presented significantly higher antibody concentration at T1 and T2. A longer interval between previous infection and vaccination was associated with a better antibody response over time. Discussion: In a frail sample of NH residents, prior SARS-CoV-2 infection was associated with a higher humoral response to vaccination. Number of vaccine doses and the interval between infection and vaccination are relevant parameters in determining humoral immunity. Conclusions: These findings provide important information to plan future immunization policies and disease prevention strategies in a highly vulnerable population. [ABSTRACT FROM AUTHOR]

With SARS-CoV-2 infection, pregnant women may be at a high risk of severe disease and adverse perinatal outcomes. A COVID-19 vaccination campaign represents the key strategy to combat the pandemic; however, public acceptance of maternal immunization has to be improved, which may be achieved by highlighting the promising mechanism of passive immunity as a strategy for protecting newborns against SARS-CoV-2 infection. We tested the anti-SARS-CoV-2 antibody response following COVID-19 full-dose vaccination in the serum and amniotic fluid of two pregnant women who presented between April and June 2021, at the Center for the Treatment and Prevention of Infections in Pregnancy of the National Institute for Infectious Diseases "L. Spallanzani", for antenatal consultancy. Anti-SARS-CoV-2 IgG was found in residual samples of amniotic fluid collected from both women at the 18th week of gestation (63 and 131 days after the second dose's administration). Titers in amniotic fluid mirrored the levels detected in serum and were inversely linked to the time from vaccination. Our results suggest that antibodies elicited by COVID-19 vaccination can cross the placenta and reach the fetus; therefore, they may offer passive immunity at birth. It is critical to fully understand the kinetics of the maternal response to vaccination, the efficiency of IgG transfer, and the persistence of antibodies in infants to optimize maternal immunization regimens. [ABSTRACT FROM AUTHOR]

In order to determine the humoral protective response against SARS-CoV-2, the vaccine-induced and naturally induced neutralizing antibodies (NtAbs) responses against SARS-CoV-2 variants circulating in Italy through in vitro live virus neutralization assay were evaluated. A total of 39 SARS-CoV-2 recovered subjects (COVID-19+) and 63 subjects with a two-dose cycle of the BNT16262 vaccine were enrolled. A single serum sample was tested for COVID-19+ at 35–52 days post-positive swab, while vaccinees blood samples were taken at one (V1) and at three months (V3) after administration of the second vaccine dose. Significantly higher NtAb titers were found against B.1 and Alpha in both COVID-19+ and vaccinees, while lower NtAb titers were detected against Delta, Gamma, and Omicron variants. A comparison between groups showed that NtAb titers were significantly higher in both V1 and V3 than in COVID-19+, except against the Omicron variant where no significant difference was found. COVID-19+ showed lower neutralizing titers against all viral variants when compared to the vaccinees. Two-dose vaccination induced a sustained antibody response against each analyzed variant, except for Omicron. The evolution process of SARS-CoV-2, through variants originating from an accumulation of mutations, can erode the neutralizing effectiveness of natural and vaccine-elicited immunity. Therefore, a need for new vaccines should be evaluated to contain the ongoing pandemic. [ABSTRACT FROM AUTHOR]

Due to potentially immune-escaping virus variants and waning immunity, a third SARS-CoV-2 vaccination dose is increasingly recommended. However, data in patients with cancer are limited. We measured anti-SARS-CoV-2 spike protein antibody levels after the third vaccination dose in 439 patients with cancer and 41 health care workers (HCW) at an academic centre in Austria and a rural community hospital in Italy. Adverse events were retrieved from questionnaires. Overall, 439 patients and 41 HCW were included. SARS-CoV-2 infections were observed in 62/439 (14.1%) patients before vaccination and in 5/439 (1.1%) patients after ≥1 dose. Longitudinal analysis revealed a decrease of antibody levels between 3 and 6 months after second vaccination in patients with solid tumours (p < 0.001) and haematological malignancies without anti-B cell therapies (p < 0.001). After the third dose, anti-S levels increased compared to the first/second dose. Patients receiving B cell-targeted agents had lower antibody levels than patients with haematological malignancies undergoing other treatments (p < 0.001) or patients with solid tumours (p < 0.001). Moreover, anti-S levels correlated with CD19+ (B cell) and CD56+ (NK cell) counts in peripheral blood. The most frequent adverse events after the third dose were local pain (75/160, 46.9%), fatigue (25/160, 15.6%) and fever/chills (16/160, 10.0%). Patients with cancer had lower anti-S levels than HCW (p = 0.015). This study in patients with cancer shows improved antibody levels after the third vaccination dose at an acceptable side-effect profile. Lower antibody levels than in controls underline the need for further follow-up studies and dedicated trials. • Anti-SARS-CoV-2 antibody levels diminished over time after the second vaccination. • Antibody levels increased after the third dose, supporting its administration. • Patients under B cell-targeting therapy showed considerably lower antibody levels. • Antibody levels correlated with CD19+ and CD56+ peripheral blood cell counts. • Lower antibody levels than in controls underline the need for further studies. [ABSTRACT FROM AUTHOR]

Background: Extensive vaccination against severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) is now universally regarded as one of the most effective strategies for counteracting the current pandemic. The durability of the immune response of available vaccines is not known, therefore the quantitative dynamics of serum anti-S antibodies after Comirnaty vaccine in health care workers (HCW) of Desio Hospital was conducted. Methods: 51 previously infected and 198 not infected HCW, from Desio, Italy were enrolled in the study. Comirnaty double dose schedule was completed by each subject. Specific anti-S antibodies against the SARS-CoV-2 S protein were measured by ECLIA in sequential blood samples. Results: A significant difference was observed beginning at pre priming dose (T0) of the anti-S antibodies between the two subgroups which persisted throughout the study (4months). A significant reduction occurred after 4months post-priming dose (T3). Finally, a subgroup of low and late responders with an increasing trend was found. Conclusions: Specific anti-S antibodies are significantly decreased 4months post priming dose of Comirnaty vaccine although prior COVID-19 infection seems to escalate humoral response. Further evaluation concerning antibody persistence beyond this point, and the proportion of neutralizing antibodies with higher affinity towards SARS-CoV-2 is needed, especially in na? ve and immunosuppressed subjects. [ABSTRACT FROM AUTHOR]

Introduction: Data have suggested that SARS-CoV-2 infection causes an antibody response at least as strong as one BNT162b2 vaccine dose. Nevertheless, some aspects require further investigation to better understand the immunogenicity of one vaccine dose among infected individuals. Thus, we evaluated how previous SARS-CoV-2 infection may influence the humoral immunity after a single Pfizer BNT162b mRNA vaccine dose in a sample of healthcare workers (HCWs). Methods: As part of the routine surveillance activity conducted among HCWs of the Policlinico Riuniti Foggia Hospital (Apulia region, Italy), we conducted a retrospective serosurvey in the period January–March 2021. We compared specific antibody titres (anti-spike IgGs measured by enzyme-linked immunoassay, ELISA) after SARS-CoV-2 infection and after the first dose of the BNT162b2 vaccine, analysing the impact of sex, age, time since infection, and presence of symptoms on the humoral response. Results: We included in the study 58 HCWs (mean age 44.1 years, 48.2% male) with anti-spike IgG titres available before and after the first BNT162b2 vaccine dose. Among these, we observed higher titres in previously infected cases (N = 21) than in COVID-19-naïve subjects (N = 37) (medians 1510 vs. 0.68; p < 0.001). A statistically significant difference in anti-spike IgG titres was also observed among previously infected HCWs before vaccine dose in comparison with post-dose infection-naïve HCWs (medians 18.37 vs. 0.68, p < 0.001). Among infected individuals, no differences by sex, age, or time since infection were reported (p > 0.05). Post-dose titres of symptomatic and asymptomatic infected HCWs slightly differed (medians = 1900 vs. 1090; p = 0.048). Conclusion: Our data support the viable hypothesis of a single-dose vaccine regimen in individuals with a history of COVID-19, but no conclusion on duration of protection in this group can be drawn from our study. [ABSTRACT FROM AUTHOR]

Background: COVID-19 vaccines have demonstrated effectiveness in reducing SARS-CoV-2 mild and severe outcomes. In vaccinated subjects with SARS-CoV-2 history, RBD-specific IgG and pseudovirus neutralization titers were rapidly recalled by a single BTN162b2 vaccine dose to higher levels than those in naïve recipients after the second dose, irrespective of waning immunity. In this study, we inspected the long-term kinetic and neutralizing responses of S-specific IgG induced by two administrations of BTN162b2 vaccine in infection-naïve subjects and in subjects previously infected with SARS-CoV-2.Methods: Twenty-six naïve and 9 previously SARS-CoV-2 infected subjects during the second wave of the pandemic in Italy were enrolled for this study. The two groups had comparable demographic and clinical characteristics. By means of ELISA and pseudotyped-neutralization assays, we investigated the kinetics of developed IgG-RBD and their neutralizing activity against both the ancestral D614G and the SARS-CoV-2 variants of concern emerged later, respectively. The Wilcoxon matched pair signed rank test and the Kruskal-Wallis test with Dunn's correction for multiple comparison were applied when needed.Results: Although after 15 weeks from vaccination IgG-RBD dropped in all participants, naïve subjects experienced a more dramatic decline than those with previous SARS-CoV-2 infection. Neutralizing antibodies remained higher in subjects with SARS-CoV-2 history and conferred broad-spectrum protection.Conclusions: These data suggest that hybrid immunity to SARS-CoV-2 has a relevant impact on the development of IgG-RBD upon vaccination. However, the rapid decay of vaccination-elicited antibodies highlights that the administration of a third dose is expected to boost the response and acquire high levels of cross-neutralizing antibodies. [ABSTRACT FROM AUTHOR]

This contribution explores in a new statistical perspective the antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 141 coronavirus disease 2019 (COVID-19) patients exhibiting a broad range of clinical manifestations. This cohort accurately reflects the characteristics of the first wave of the SARS-CoV-2 pandemic in Italy. We determined the IgM, IgA, and IgG levels towards SARS-CoV-2 S1, S2, and NP antigens, evaluating their neutralizing activity and relationship with clinical signatures. Moreover, we longitudinally followed 72 patients up to 9 months postsymptoms onset to study the persistence of the levels of antibodies. Our results showed that the majority of COVID-19 patients developed an early virus-specific antibody response. The magnitude and the neutralizing properties of the response were heterogeneous regardless of the severity of the disease. Antibody levels dropped over time, even though spike reactive IgG and IgA were still detectable up to 9 months. Early baseline antibody levels were key drivers of the subsequent antibody production and the long-lasting protection against SARS-CoV-2. Importantly, we identified anti-S1 IgA as a good surrogate marker to predict the clinical course of COVID-19. Characterizing the antibody response after SARS-CoV-2 infection is relevant for the early clinical management of patients as soon as they are diagnosed and for implementing the current vaccination strategies. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the possible impact of smoking on the humoral response to the BNT162b2 mRNA COVID-19 vaccine (also known as the BioNTech-Pfizer COVID-19 vaccine). A longitudinal sero-epidemiological study was conducted in sample of Italian healthcare workers (HCWs). HCWs who were administered two doses of the BNT162b2 mRNA vaccine, 21 days apart, between December 2020 and January 2021, were invited to undergo multiple serology tests to identify SARS-CoV-2 S-RBD-specific immunoglobulin G (IgG) antibodies. Participants also responded to questions about their smoking status (i.e. current smokers vs non-smokers) in a survey. Sixty days after the completion of the vaccination cycle, serological analyses showed a difference in vaccine-induced IgG titre between current smokers and non-smokers, with median antibody titres of 211.80 AU/mL (interquartile range [IQR] 149.80–465.50) and 487.50 AU/mL (IQR 308.45–791.65) [ P -value = 0.002], respectively. This significant difference in vaccine-induced IgG titres between current smokers and non-smokers remained after adjusting for age, sex, and previous infection with SARS-CoV-2. This study observed that vaccine-induced antibody titres decrease faster among current smokers than non-smokers. Further research to investigate the impact of smoking on the immunological response to COVID-19 and non-COVID-19 vaccines is required. [ABSTRACT FROM AUTHOR]

Background The pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains unclear. We report the detection of viral RNA from different anatomical districts and the antibody profile in the first 2 COVID-19 cases diagnosed in Italy. Methods We tested for SARS-CoV-2 RNA clinical samples, either respiratory and nonrespiratory (ie, saliva, serum, urine, vomit, rectal, ocular, cutaneous, and cervico-vaginal swabs), longitudinally collected from both patients throughout the hospitalization. Serological analysis was carried out on serial serum samples to evaluate IgM, IgA, IgG, and neutralizing antibody levels. Results SARS-CoV-2 RNA was detected since the early phase of illness, lasting over 2 weeks in both upper and lower respiratory tract samples. Virus isolate was obtained from acute respiratory samples, while no infectious virus was rescued from late respiratory samples with low viral RNA load, collected when serum antibodies had been developed. Several other specimens came back positive, including saliva, vomit, rectal, cutaneous, cervico-vaginal, and ocular swabs. IgM, IgA, and IgG were detected within the first week of diagnosis, with IgG appearing earlier and at higher titers. Neutralizing antibodies developed during the second week, reaching high titers 32 days after diagnosis. Conclusions Our longitudinal analysis showed that SARS-CoV-2 RNA can be detected in different body samples, which may be associated with broad tropism and different spectra of clinical manifestations and modes of transmission. Profiling antibody response and neutralizing activity can assist in laboratory diagnosis and surveillance actions. [ABSTRACT FROM AUTHOR]

• MenACYW-TT was non-inferior to MCV4-CRM in meningococcal vaccine-naive adolescents. • Immunogenicity of MenACYW-TT was unaffected by co-administration with Tdap and HPV4. • The proportion of subjects with seroprotection was higher for MenACYW-TT vs MCV4-CRM. • MenACYW-TT was well tolerated, with or without Tdap and HPV4 co-administration. MenACYW-TT is an investigational quadrivalent meningococcal conjugate vaccine intended for use in individuals ≥6 weeks of age. We evaluated the safety and immunogenicity of MenACYW-TT when compared to a licensed quadrivalent conjugate meningococcal vaccine (Menveo®; MCV4-CRM; GlaxoSmithKline, Italy), and when co-administered with tetanus, diphtheria, acellular pertussis (Tdap) and human papilloma virus (HPV4) vaccines in healthy meningococcal vaccine-naïve adolescents (10–17 years old) in the United States of America. In this pivotal Phase II, open-label, multicenter study, 1715 participants were randomized to receive MenACYW-TT, MCV4-CRM, MenACYW-TT co-administered with Tdap and HPV4, or Tdap and HPV4 vaccines alone (NCT02199691). The primary objective was to evaluate whether antibody responses to MenACYW-TT antigens were non-inferior to antibody responses after MCV4-CRM administration. Meningococcal antibody titers were determined using human complement serum bactericidal assay (hSBA) with titers measured at baseline, and 30 days post vaccination (D30). A vaccine seroresponse was defined as baseline titers <1:8 with post-vaccination titers ≥1:8 or baseline titers ≥1:8 with a ≥4-fold increase at post-vaccination. Safety data were collected up to six months post-vaccination. Non-inferiority was demonstrated for MenACYW-TT vs MCV4-CRM (primary endpoint), and for MenACYW-TT co-administered with Tdap and HPV4 vs MenACYW-TT alone (secondary endpoint). The vaccine seroresponse rate was higher with MenACYW-TT than with MCV4-CRM, for each serogroup: A: 75.6% vs 66.4%; C: 97.2% vs 72.6%; W: 86.2% vs 66.6%; Y: 97.0% vs 80.8%. The safety profiles of MenACYW-TT, MCV4-CRM, and Tdap and HPV4 vaccines, administered with or without MenACYW-TT, were comparable. There were no vaccine-related serious adverse events. The MenACYW-TT vaccine was well tolerated and generated an immune response that was non-inferior to the licensed MCV4-CRM vaccine. Immunogenicity and safety profiles were comparable when MenACYW-TT was administered with or without Tdap and HPV4 vaccines in meningococcal vaccine-naïve adolescents. [ABSTRACT FROM AUTHOR]

Background: Fabry disease is a rare progressive X-linked lysosomal storage disease caused by mutations in the GLA gene that encodes α-galactosidase A. Agalsidase beta is a recombinant enzyme replacement therapy authorized in Europe at a standard dose of 1.0 mg/kg intravenously every other week at an initial infusion rate of ≤ 0.25 mg/min until patient tolerance is established, after which the infusion rate may be increased gradually. However, specific practical guidance regarding the progressive reduction in infusion time is lacking. This study investigated a new and specific protocol for reducing agalsidase beta infusion time in which a stable dosage of 15 mg/h is infused for the first four months, and the infusion rate is increased progressively from 15 to 35 mg/h for the subsequent four infusions. The shortest infusion time is reached after six months and maintained thereafter. The incidence of infusion-associated reactions (IARs) and the development of anti-drug antibodies were analyzed, and the disease burden and the clinical evolution of the disease at 12 months were evaluated., Results: Twenty-five of the 31 patients were naïve to enzyme or chaperone treatment at baseline and six patients had been switched from agalsidase alfa. The reduced infusion time protocol was well tolerated. Only one patient exhibited an IAR, with mild symptoms that resolved with low-dose steroids. Six patients globally seroconverted during treatment (4 with a classic phenotype and 2 with late-onset disease). All but three patients were seronegative at month 12. All patients were stable at the study's end (FAbry STabilization indEX value < 20%); reducing infusion time did not negatively impact clinical outcomes in any patient. The perceived medical assessment showed that the quality of life of all patients improved., Conclusions: The study demonstrates that reducing agalsidase beta infusion time is possible and safe from both an immunogenic and clinical point of view. The use of a low infusion rate in the first months when the probability of onset of the development of antibodies is higher contributed to very limited seroconversion to antibody-positive status., (© 2024. The Author(s).)

Human antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hold intense interest, with research efforts directed at optimizing antibody-based interventions and monitoring immune status. By relating individual variations in antibody response to coronavirus disease 2019 (COVID-19) severity, beneficial antiviral immune responses may be identified in detail. In this issue of the JCI, Secchi and collaborators describe antibody response profiles in 509 patients with COVID-19 from Italy during the 2020 pandemic. The research team found that multiple antibody types to multiple SARS-CoV-2 antigens developed over four weeks. Notably, IgG against the spike receptor binding domain (RBD) was predictive of survival and IgA against the viral spike protein (S protein) associated with rapid virologic clearance. These results may help guide selection of convalescent plasma, hyperimmune products, monoclonal antibodies, and vaccine strategies for COVID-19. [ABSTRACT FROM AUTHOR]

In January 2015, during a 3-week period, 12 captive Tonkean macacques at a sanctuary in Italy died. An orthopoxvirus infection was suspected because of negative-staining electron microscopy results. The diagnosis was confirmed by histology, virus isolation, and molecular analysis performed on different organs from all animals. An epidemiologic investigation was unable to define the infection source in the surrounding area. Trapped rodents were negative by virologic testing, but specific IgG was detected in 27.27% of small rodents and 14.28% of rats. An attenuated live vaccine was administered to the susceptible monkey population, and no adverse reactions were observed; a detectable humoral immune response was induced in most of the vaccinated animals. We performed molecular characterization of the orthopoxvirus isolate by next-generation sequencing. According to the phylogenetic analysis of the 9 conserved genes, the virus could be part of a novel clade, lying between cowpox and ectromelia viruses. [ABSTRACT FROM AUTHOR]

In January 2015, during a 3-week period, 12 captive Tonkean macacques at a sanctuary in Italy died. An orthopoxvirus infection was suspected because of negative-staining electron microscopy results. The diagnosis was confirmed by histology, virus isolation, and molecular analysis performed on different organs from all animals. An epidemiologic investigation was unable to define the infection source in the surrounding area. Trapped rodents were negative by virologic testing, but specific IgG was detected in 27.27% of small rodents and 14.28% of rats. An attenuated live vaccine was administered to the susceptible monkey population, and no adverse reactions were observed; a detectable humoral immune response was induced in most of the vaccinated animals. We performed molecular characterization of the orthopoxvirus isolate by next-generation sequencing. According to the phylogenetic analysis of the 9 conserved genes, the virus could be part of a novel clade, lying between cowpox and ectromelia viruses. [ABSTRACT FROM AUTHOR]

The study aim was to assess predictors of negative antibody response (AbR) in solid organ transplant (SOT) recipients after the first booster of SARS-CoV-2 vaccination. Solid organ transplant recipients receiving SARS-CoV-2 vaccination were prospectively enrolled (March 2021–January 2022) at six hospitals in Italy and Spain. AbR was assessed at first dose (t 0), second dose (t 1), 3 ± 1 month (t 2), and 1 month after third dose (t 3). Negative AbR at t 3 was defined as an anti-receptor binding domain titre <45 BAU/mL. Machine learning models were developed to predict the individual risk of negative (vs. positive) AbR using age, type of transplant, time between transplant and vaccination, immunosuppressive drugs, type of vaccine, and graft function as covariates, subsequently assessed using a validation cohort. Overall, 1615 SOT recipients (1072 [66.3%] males; mean age±standard deviation [SD], 57.85 ± 13.77) were enrolled, and 1211 received three vaccination doses. Negative AbR rate decreased from 93.66% (886/946) to 21.90% (202/923) from t 0 to t 3. Univariate analysis showed that older patients (mean age, 60.21 ± 11.51 vs. 58.11 ± 13.08), anti-metabolites (57.9% vs. 35.1%), steroids (52.9% vs. 38.5%), recent transplantation (<3 years) (17.8% vs. 2.3%), and kidney, heart, or lung compared with liver transplantation (25%, 31.8%, 30.4% vs. 5.5%) had a higher likelihood of negative AbR. Machine learning (ML) algorithms showing best prediction performance were logistic regression (precision-recall curve-PRAUC mean 0.37 [95%CI 0.36–0.39]) and k-Nearest Neighbours (PRAUC 0.36 [0.35–0.37]). Almost a quarter of SOT recipients showed negative AbR after first booster dosage. Unfortunately, clinical information cannot efficiently predict negative AbR even with ML algorithms. [ABSTRACT FROM AUTHOR]

Background: COVID-19 has hit every country in the world. Almost a quarter of a billion cases and nearly 5 million deaths reported globally as of late September 2021. Compared to over 6 billion doses of COVID-19 vaccine administered, the pandemic does not seem to disappear. The duration of protective immunity is currently not defined. Primary immune responses are inevitably declining and the continuous transmission of increasingly worrying viral variants., Objective: The primary objective of the study is to evaluate the antibody response at 120 and 180 days in employees of an hospital of Marche (Italy) who have completed the vaccination cycle with Pzifer-Biontech vaccine and to highlight the correlation with quantitative and qualitative variables. The secondary objective is to study the nature and frequency of adverse events in relation to variables such as comorbidity, age, gender, working areas and developed antibody titer., Materials and Methods: An observational retrospective study was carried out to evaluate the antibody response at 120 and 180 days. Subjects receiving a double dose of vaccine at least 21 days apart and those receiving the second dose of the same vaccine between 18 January 2021 and 31 March 2021 shall be considered. The study included non-probability sampling of convenience. All parties have provided informed written consent to access personal and clinical data., Results: The sample is composed by 1.115 subjects. The results of the study reveal an important immune response detected by IgG dosage, both at 120 and 180 days after the second dose of Sars-Cov-2 vaccine mRNA BNT162b2 vaccine (Pzifer-Biontech), other than very rare exceptions. Antibody values are higher among hospital workers compared to those working in other areas, both 120 and 180 days. These values are even higher in the health professionals who provide assistance in wards with positive Covid patients, both at 120 days (p=0.06) and at 180 days; the mean values of IgG are statistically higher in direct assistance of Covid patients at 180 days(p=0.029). The most frequent adverse drug events after the second dose of vaccine were pain at the site of inoculation of the vaccine (70.7%), fatigue (35%) and arthralgia (19%). It was finally shown that people with diabetes or smokers had an average antibody response statistically lower than 120 days and 180 days from the second dose., Discussion and Conclusion: This study leads to the conclusion that the second dose of vaccine Sars-Cov-2 vaccine mRNA BNT162b2 vaccine allows a consistent antibody response. Further multicentric studies are needed to investigate the antibody response to vaccination Sars-Cov-2 mRNA BNT162b2.

Bats are natural reservoirs for many mammalian coronaviruses, which have received renewed interest after the discovery of the severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS) CoV in humans. This study describes the identification and molecular characterization of alphacoronaviruses and betacoronaviruses in bats in Italy, from 2010 to 2012. Sixty-nine faecal samples and 126 carcasses were tested using pan-coronavirus RT-PCR. Coronavirus RNAs were detected in seven faecal samples and nine carcasses. A phylogenetic analysis of RNA-dependent RNA polymerase sequence fragments aided in identifying two alphacoronaviruses from Kuhl's pipistrelle (Pipistrellus kuhlii), three clade 2b betacoronaviruses from lesser horseshoe bats (Rhinolophus hipposideros), and 10 clade 2c betacoronaviruses from Kuhl's pipistrelle, common noctule (Nyctalus noctula), and Savi's pipistrelle (Hypsugo savii). This study fills a substantive gap in the knowledge on bat-CoV ecology in Italy, and extends the current knowledge on clade 2c betacoronaviruses with new sequences obtained from bats that have not been previously described as hosts of these viruses. [ABSTRACT FROM AUTHOR]

Background: Phlebotomine sand flies are blood-sucking insects that can transmit Leishmania parasites. Hosts bitten by sand flies develop an immune response against sand fly salivary antigens. Specific anti-saliva IgG indicate the exposure to the vector and may also help to estimate the risk of Leishmania spp. transmission. In this study, we examined the canine antibody response against the saliva of Phlebotomus perniciosus, the main vector of Leishmania infantum in the Mediterranean Basin, and characterized salivary antigens of this sand fly species. Methodology/Principal Findings: Sera of dogs bitten by P. perniciosus under experimental conditions and dogs naturally exposed to sand flies in a L. infantum focus were tested by ELISA for the presence of anti-P. perniciosus antibodies. Antibody levels positively correlated with the number of blood-fed P. perniciosus females. In naturally exposed dogs the increase of specific IgG, IgG1 and IgG2 was observed during sand fly season. Importantly, Leishmania-positive dogs revealed significantly lower anti-P. perniciosus IgG2 compared to Leishmania-negative ones. Major P. perniciosus antigens were identified by western blot and mass spectrometry as yellow proteins, apyrases and antigen 5-related proteins. Conclusions: Results suggest that monitoring canine antibody response to sand fly saliva in endemic foci could estimate the risk of L. infantum transmission. It may also help to control canine leishmaniasis by evaluating the effectiveness of anti-vector campaigns. Data from the field study where dogs from the Italian focus of L. infantum were naturally exposed to P. perniciosus bites indicates that the levels of anti-P. perniciosus saliva IgG2 negatively correlate with the risk of Leishmania transmission. Thus, specific IgG2 response is suggested as a risk marker of L. infantum transmission for dogs. Author Summary: Leishmania infantum is the causative agent of zoonotic visceral leishmaniasis in the Mediterranean Basin and Phlebotomus perniciosus serve as the major vector. In the endemic foci, Leishmania parasites are transmitted mostly to dogs, the main reservoir host, and to humans. We studied the canine humoral immune response to Phlebotomus perniciosus saliva and its potential use as a marker of sand fly exposure and consequently as a risk marker for Leishmania transmission. We also characterized major salivary antigens of P. perniciosus. We demonstrated that under laboratory conditions, the levels of anti-P. perniciosus saliva antibodies positively correlated with the number of blood-fed sand flies and therefore, may be used to evaluate the need for, and the effectiveness of, anti-vector campaigns. In parallel, we studied sera of dogs naturally exposed to P. perniciosus in highly active focus of canine leishmaniasis in Southern Italy. Specific antibodies against P. perniciosus saliva were significantly increased according to the ongoing sand fly season. Moreover, the levels of anti-P. perniciosus antibodies in naturally bitten dogs negatively correlated with anti-Leishmania seropositivity. Thus, for dogs living in endemic areas, specific antibody response against saliva of the vector is an important marker for estimating the risk of Leishmania transmission. [ABSTRACT FROM AUTHOR]

The Pfizer/BioNtech Comirnaty vaccine (BNT162b2 mRNA COVID-19) against SARS-CoV-2 is currently in use in Italy. Antibodies to evaluate SARS-CoV-2 infection prior to administration are not routinely tested; therefore, two doses may be administered to asymptomatic previously exposed subjects. The aim of this study is to assess if any difference in antibody concentration between subjects exposed and not exposed to SARS-CoV-2 prior to BNT162b2 was present after the first dose and after the second dose of vaccine. Data were retrospectively collected from the clinical documentation of 337 healthcare workers who underwent SARS-CoV-2 testing before and after BNT162b2. Total anti RBD (receptor-binding domain) antibodies against SARS-CoV-2′s spike protein were measured before and 21 days after the first dose, and 12 days after the second dose of BNT162b2. Twenty-one days after the first dose, there was a statistically significant difference in antibody concentration between the two groups, which was also maintained twelve days after the second dose. In conclusion, antibody response after receiving BNT162b2 is greater in subjects who have been previously exposed to SARS-CoV-2 than in subjects who have not been previously exposed to the virus, both after 21 days after the first dose and after 12 days from the second dose. Antibody levels, 21 days after the first dose, reached a titer considered positive by the test manufacturer in the majority of subjects who have been previously infected with SARS-CoV-2. Evaluating previous infection prior to vaccination in order to give the least effective number of doses should be considered. [ABSTRACT FROM AUTHOR]

Better understanding of antibody responses against SARS-CoV-2 after natural infection might provide valuable insights into the future implementation of vaccination policies. Longitudinal analysis of IgG antibody titers was carried out in 32 recovered COVID-19 patients based in the Umbria region of Italy for 14 months after Mild and Moderately-Severe infection.Two FDA-approved immunoassays against SARS-CoV-2 Nucleocapsid protein (NCP) and anti-spike-receptor binding domain (S-RBD) were used for sequential serological tests at different time points. The demographics,clinical history and symptom profile associated with the magnitude and longevity of antibody responses were also analyzed. Anti-S-RBD IgG persisted in 96.8% (31 of 32) subjects at 14 months. Patients reporting loss of smell and taste during the clinical course of the disease developed significantly higher antibody titers. Anti-NCP IgG seronegative patients(n =7) at 10 months, tested positive for anti-S-RBD IgG at 12,13 and 14 months emphasizing on a higher false-negative rate for NCP protein-based antibody assays. This study also highlights the importance of adopting specific immunoassays for routine estimation of antibody titers and the decreased rate of re-infections in recovered patients. [Display omitted] • An understanding of antibody responses post SARS-CoV-2 natural infection is crucial for future health policy implementation • Anti-Spike-Receptor Binding Domain antibodies persisted in 96.8% (31 of 32) subjects at 14 months post natural infection • Patients reporting loss of smell and taste during the period of infection developed significantly higher antibody titers • Nucleocapsid protein-based antibody assays demonstrate higher false-negative rates and should be avoided in routine analysis [ABSTRACT FROM AUTHOR]

Since the coronavirus disease (COVID-19) pandemic was first identified in early 2020, rare cases of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in pet cats have been reported worldwide. Some reports of cats with SARS-CoV-2 showed self-limiting respiratory or gastrointestinal disease after suspected human-to-feline transmission via close contact with humans with SARS-CoV-2. In the present study, we investigated a cat with SARS-CoV-2 that was presented to a private animal clinic in Northern Italy in May 2020 in a weak clinical condition due to an underlying intestinal B-cell lymphoma. The cat developed signs of respiratory tract disease, including a sneeze, a cough and ocular discharge, three days after an oropharyngeal swab tested positive for SARS-CoV-2 viral RNA using two real-time reverse transcriptase polymerase chain reaction (RT-qPCR) assays for the envelope (E) and RNA-dependent RNA polymerase (RdRp) gene. Thus, SARS-CoV-2 viral RNA was detectable prior to the onset of clinical signs. Five and six months after positive molecular results, the serological testing substantiated the presence of a SARS-CoV-2 infection in the cat with the detection of anti-SARS-CoV-2 receptor binding domain (RBD) immunoglobulin (IgG) antibodies and neutralizing activity in a surrogate virus neutralization assay (sVNT). To the best of our knowledge, this extends the known duration of seropositivity of SARS-CoV-2 in a cat. Our study provides further evidence that cats are susceptible to SARS-CoV-2 under natural conditions and strengthens the assumption that comorbidities may play a role in the development of clinical disease. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) persistent infections are associated with cervical cancer and other HPV-related diseases and tumors. Thus, the characterization of long lasting immunity to currently available HPV vaccines is important. A total of 149 female subjects vaccinated with Cervarix or Gardasil participated to the study and they were stratified according to age (10–12-year-old and 16–20-year-old). Humoral immune responses (IgG and neutralizing antibody titers, antibody avidity) and circulating memory B cells were analyzed after an average of 4–6 years from the third immunization. The humoral responses against HPV-16 and HPV-18 (and HPV-6 and HPV-11 for Gardasil) were high in both age groups and vaccines up to six years from the third dose. However, Cervarix induced significantly higher and more persistent antibody responses, while the two vaccines were rather equivalent in inducing memory B cells against HPV-16 and HPV-18. Moreover, the percentage of subjects with vaccine-specific memory B cells was even superior among Gardasil vaccinees and, conversely, Cervarix vaccinated individuals with circulating antibodies, but undetectable memory B cells were found. Finally, a higher proportion of Cervarix-vaccinated subjects displayed cross-neutralizing responses against non-vaccine types HPV-31 and HPV-45. Gardasil and Cervarix may, thus, differently affect long-lasting humoral immunity from both the quantitative and qualitative point of view. [ABSTRACT FROM AUTHOR]

Mosquitoes of the Aedes genus transmit arboviruses of great importance to human health as dengue, chikungunya, Zika and yellow fever. The tiger mosquito Aedes albopictus can play an important role as arboviral vector, especially when Aedes aegypti is absent or present at low levels. Remarkably, the rapid worldwide spreading of the tiger mosquito is expanding the risk of arboviral transmission also to temperate areas, and the autochthonous cases of chikungunya, dengue and Zika in Europe emphasize the need for improved monitoring and control. Proteomic and transcriptomic studies on blood feeding arthropod salivary proteins paved the way toward the exploitation of genus-specific mosquito salivary proteins for the development of novel tools to evaluate human exposure to mosquito bites. We previously found that the culicine-specific 34k2 salivary protein from Ae. albopictus (al34k2) evokes specific IgG responses in experimentally exposed mice, and provided preliminary evidence of its immunogenicity to humans. In this study we measured IgG responses to al34k2 and to Ae. albopictus salivary gland protein extracts (SGE) in individuals naturally exposed to the tiger mosquito. Sera were collected in two areas of Northeast Italy (Padova and Belluno) during two different time periods: at the end of the low- and shortly after the high-density mosquito seasons. Anti-SGE and anti-al34k2 IgG levels increased after the summer period of exposure to mosquito bites and were higher in Padova as compared to Belluno. An age-dependent decrease of anti-saliva IgG responses was found especially in Padova, an area with at least 25 years history of Ae. albopictus colonization. Moreover, a weak correlation between anti-saliva IgG levels and individual perception of mosquito bites by study participants was found. Finally, determination of anti-al34k2 IgG1 and IgG4 levels indicated a large predominance of IgG1 antibodies. Overall, this study provides a convincing indication that antibody responses to al34k2 may be regarded as a reliable candidate marker to detect temporal and/or spatial variation of human exposure to Ae. albopictus ; a serological tool of this kind may prove useful both for epidemiological studies and to estimate the effectiveness of anti-vectorial measures., (Copyright © 2020 Buezo Montero, Gabrieli, Montarsi, Borean, Capelli, De Silvestro, Forneris, Pombi, Breda, Capelli and Arcà.)

Mycobacterium avium subspecies paratuberculosis (MAP) asymptomatic infection is speculated to play a role in type 1 diabetes (T1D) among Sardinian subjects. Data obtained analyzing a pediatric population from mainland Italy lends support to the hypothesis, which envisions MAP as an environmental factor at play in T1D pathogenesis. Aiming to investigate the likelihood of cross-recognition between linear determinants shared by self (proinsulin) and non-self (MAP) proteins, 59 children with new onset T1D and 60 healthy controls (HCs) from continental Italy were enrolled in the study. Serum samples were subjected to indirect enzyme-linked immunosorbent assay (ELISA) for the presence of antibodies (Abs) toward four homologues MAP/proinsulin epitopes. The rate of MAP infection (42.4% in T1D children and 5% in HCs; p < 0.0001) was estimated searching for Abs against MAP specific protein MptD. The homologous MAP2404c70-85 and proinsulin (PI)46-61 peptides were recognized by 42.4 and 39% of new-onset T1D children and only in 5% of HCs (AUC = 0.76, AUC = 0.7, p < 0.0001); whereas the prevalence of Abs against MAP 1,4-α-gbp157-173 and PI64-80 peptides was 45.7 and 49.1% in new-onset T1D children, respectively, compared with 3.3% of HCs (AUC = 0.74 and p < 0.0001 in both). Pre-incubation of MAP Ab-positive sera with proinsulin peptides was able to block the binding to the correspondent MAP epitopes, thus showing that Abs against these homologous peptides are cross-reactive. MAP/Proinsulin Ab mediated cross-recognition, most likely via molecular mimicry, maybe a factor in accelerating and/or initiating T1D in MAP-infected children. Indeed, it is known that anti-proinsulin and anti-Insulin autoantibodies are the earliest to appear., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Mycobacterium avium subspecies paratuberculosis (MAP) is associated with MS in Sardinia. Because anti-MAP antibodies (Abs) were more frequent in interferon-beta treated patients, we hypothesize that interferon-beta could interact with the immune system., Methods: Anti-MAP Abs were searched in the blood of 89 patients before commencing interferon-beta and after at least six months., Results: Anti-MAP Abs were detected before and during treatment in 18.7% and 34.7% of patients, respectively. Twenty-three (20.5%) patients became positive during therapy, and 5 (4.4%) patients became negative (p=0.001)., Conclusions: The study supports the hypothesis that interferon-beta could interact with the immune system, enhancing the immunological response against MAP., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Little is known about the proportion of pediatric pandemic A/H1N1/2009 influenza cases who showed seroconversion, the magnitude of this seroconversion, or the factors that can affect the antibody level evoked by the pandemic A/H1N1/2009 influenza. Aims of this study were to analyse antibody responses and the factors associated with high antibody titres in a cohort of children with naturally acquired A/H1N1/2009 influenza infection confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR)., Results: Demographic, clinical and virologic data were collected from 69 otherwise healthy children with pandemic A/H1N1/2009 influenza (27 females, mean age ± SD: 5.01 ± 4.55 years). Their antibody levels against pandemic A/H1N1/2009 and seasonal A/H1N1 influenza viruses were evaluated by measuring hemagglutination-inhibiting antibodies using standard assays. Sixty-four patients (92.8%) with pandemic A/H1N1/2009 influenza had A/H1N1/2009 antibody levels of ≥ 40, whereas only 28/69 (40.6%) were seroprotected against seasonal A/H1N1 influenza virus. Those who were seroprotected against seasonal A/H1N1 virus were significantly older, significantly more often hospitalised, had a diagnosis of pneumonia significantly more frequently, and were significantly more often treated with oseltamivir than those who were not seroprotected (p < 0.05). The children with the most severe disease (assessed on the basis of a need for hospitalisation and a diagnosis of pneumonia) had the highest antibody response against pandemic A/H1N1/2009 influenza virus., Conclusions: Otherwise healthy children seem to show seroprotective antibody titres after natural infection with pandemic A/H1N1/2009 influenza virus. The strength of the immune response seems to be related to the severity of the disease, but not to previous seasonal A/H1N1 influenza immunity.

Background: 2009 A(H1N1) pandemic influenza vaccination was recommended as a priority to essential workers and high-risk individuals, including HIV-infected patients and people living in communities., Methods: HIV-infected and HIV-uninfected former drug-users (18-60 years old) living in a rehabilitation community (San Patrignano, Italy) received one dose of a MF59-adjuvanted 2009 pandemic influenza vaccine and one dose of a 2009-2010 seasonal trivalent inactivated influenza vaccine (containing A/Brisbane/59/2007(H1N1), A/Brisbane/10/2007(H3N2), B/Brisbane/60/2008) simultaneously. Antibodies against each vaccine antigen were determined at the time of vaccination and one and six months post-vaccination by hemagglutination-inhibition test., Results: 49 HIV-infected and 60 HIV-uninfected subjects completed the study. Most (98%) HIV-infected participants were on antiretroviral treatment, the median CD4+ cell count was 350 (IQR 300)cells/μl and viremia was suppressed in 91.8% of cases. One month post-vaccination, no significant changes in immune-virological parameters were observed. One month post-vaccination, the immune responses to both pandemic and seasonal vaccine met the EMA-CPMP criteria for immunogenicity of influenza vaccines in both HIV-infected and HIV-uninfected subjects. No difference in vaccine responses was observed between the two groups. Six months after vaccination, the percentages of vaccinees with antibody titres ≥1:40 and antibody geometric mean titres significantly decreased in both groups. However, they were significantly lower in HIV-infected than in HIV-uninfected vaccinees. In subjects who had been primed to seasonal influenza the year before (through either vaccination or natural infection), levels of antibodies against 2009 A(H1N1) were higher than those measured in unprimed subjects, both one month and six months post-vaccination., Conclusions: The co-administration of a single dose of 2009 pandemic MF59-adjuvanted influenza vaccine with a seasonal vaccine provided a protective immune response in both HIV-infected and HIV-uninfected individuals. Subjects who had been primed to seasonal influenza in the year preceding the pandemic had a more vigorous and long-lasting antibody response to 2009 pandemic vaccine., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

To assess the immunogenicity of Zulvac 8 Bovis (a commercial inactivated vaccine against bluetongue virus serotype 8 - BTV8) under field conditions, 71 cattle vaccinated according to manufacturer schedule in Verona province (Italy) were tested for the presence of BTV8 neutralizing antibodies at 21, 29, 36, 43, 49, 102 and 201 days post-vaccination (dpv). Another group of 528 BTV8 vaccinated cattle in Mantova province (Italy) was also tested once between 113 and 174 dpv. The vaccine was able to elicit an immune response in 69 (97.2%) and 346 (65.5%) animals of the Verona and Mantova groups, respectively.

To assess in Italy the pre-pandemic susceptibility of the general population to the 2009 A/H1N1v influenza virus, 587 serum samples collected in 2004 were analyzed using haemagglutination-inhibition (HI), single-radial-haemolysis (SRH) and microneutralisation (MN) assays. Serum samples were stratified by age group, gender, and geographic area. Overall, using HI assay, the proportion of subjects showing antibodies cross-reacting with 2009 A/H1N1v virus at seroprotection level (>or=1:40) was estimated to be 6.7%, 12.4%, and 22.4% in individuals born between 2004 and 1949, 1948 and 1939, 1938 and 1909, respectively. With a HI antibody titre of >or=1:10, in the same birth cohort, the seroprotection levels were 13.5%, 19.2%, and 58.2%, respectively. The results suggest that the Italian population was not fully naïf to the current pandemic virus and that the possible previous exposure and immune response increases with age., ((c) 2010 Elsevier Ltd. All rights reserved.)

Tick-borne encephalitis (TBE) virus is one of the most important flaviviruses associated with neurological disease in Europe. Cross-reactive antibodies elicited by different flaviviruses can make difficult the interpretation of ELISA and hemagglutination-inhibition (HI) tests for the diagnosis of TBE. Neutralization tests, which are more specific, are not in common use because they are difficult to perform and standardize. A plaque reduction neutralization test (PRNT), optimized previously in vaccinated children, was evaluated in sera from acute cases of TBE, collected for diagnostic purposes, and from healthy human population and wild ruminants, collected for serosurvey purposes. The PRNT results were compared with the results of ELISA and HI tests. In acute TBE disease, most sera were positive for IgM antibodies by ELISA and with high HI antibody titers; neutralizing antibodies were detected in 71.4% of patients, at a very low titer (1:10 NT(50)) in almost all cases. Seroprevalences of 8% and 6.5% for anti-TBE ELISA antibodies were found in healthy subjects and wild ruminants, respectively. Among anti-TBE positive healthy subjects, a very low 1:10 NT(50) titer was detected in 17.4% of cases, while NT(80) titers ranging from 1:10 to 1:80 were detected in 65.2% of cases. Among wild ruminants, 90.9% of ELISA and HI positive samples showed a positive, >/=1:10 NT(80) titer. In conclusion, neutralization assays can be useful for the diagnosis and serosurveys of TBE., ((c) 2009 Wiley-Liss, Inc.)

Objective: Despite multiple and repeated exposures to HIV-1, some individuals possess no detectable HIV genome and show T-cell memory responses to the viral antigens. HIV-1-reactive mucosal IgA detected in such uninfected individuals suggests their possible immune resistance against HIV. We tested if the above HIV-1-exposed but uninfected status was associated with genetic markers other than a homozygous deletion of the CCR5 gene., Methods: Based on our mapping in chromosome 15 of a gene controlling the production of neutralizing antibodies in a mouse retrovirus infection, we genotyped 42 HIV-1-exposed but uninfected Italians at polymorphic loci in the syntenic segment of human chromosome 22, and compared them with 49 HIV-1-infected and 47 uninfected healthy control individuals by a closed testing procedure., Results: A significant association was found between chromosome 22q12-13 genotypes and a putative dominant locus conferring anti-HIV-1 immune responses in the exposed but uninfected individuals. Distributions of linkage disequilibrium across chromosome 22 also differed between the exposed but uninfected and two other phenotypic groups., Conclusions: The data indicated the presence of a new genetic factor associated with the HIV-1-exposed but uninfected status.

The minimum requirements for assessing the immunogenicity of an experimental avian influenza (AI) vaccine prepared from inactivated A/Turkey/Italy/2676/99 (H7N1) low-pathogenicity (LP) AI (LPAI) virus were determined in chickens of different ages. A correlation between the amount of hemagglutinin (HA) per dose of vaccine and the protection against clinical signs of disease and infection by A/Chicken/Italy/13474/99 highly pathogenic (HP) AI (HPAI) virus was established. Depending on the vaccination schedule, one or two administrations of 0.5 microg of hemagglutinin protected chickens against clinical signs and death and completely prevented virus shedding from birds challenged at different times after vaccination.

Cystic echinococcosis caused by Echinococcus granulosus is one of the most widespread zoonoses in the Mediterranean, endemic in some regions such as Sardinia. Some aspects of the research conducted in this area are briefly reviewed for an integrated analysis of both epidemiological and immunobiological knowledge, gained from field observations and experimental studies. Data on epidemiology in intermediate hosts, immunological assessment of exposure in humans, immune response and Th1/Th2 polarization in secondary experimental hydatidosis, kinetics of response in definitive host and cytokine production in experimental models are briefly reported. They confirm the usefulness of an immunobiological approach both in intermediate and definitive hosts and their potential in prevention, monitoring and control of E/H.

Historically, considerable variation has been reported in the type and severity of clinical and hematologic abnormalities associated with canine ehrlichiosis. Because of difficulties associated with the isolation of intracellular monocytic Ehrlichia species in tissue culture systems, few E. canis isolates are available for comparative microbiologic studies. To address the issue of potential E. canis antigenic diversity in different regions of the world, dog sera reactive by indirect fluorescent antibody testing to E. canis (Florida) antigen were obtained from France, Israel, Italy, the United States, the Virgin Islands, and Zimbabwe. Ehrlichia canis proteins were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis, and at least 5 sera from each region were stained by western immunoblotting. Antibody immunodominance was scored based upon staining intensity. There was relative homogeneity in the immunogenic protein reactions to E. canis antigens. Of the 58 E. canis reactive sera, 54 samples resulted in immunoblot patterns indicative of chronic ehrlichiosis. Four reactive sera (reciprocal titers of 160-2,560) did not recognize any genus-specific antigens resulting in protein bands between 22 and 29 kD, indicating serologic cross-reactivity with other microorganisms. Relatively homogenous immunoblot patterns, consistent with the reported immunoblot response of dogs with experimental chronic ehrlichiosis, were observed with sera from Arizona, France, Israel, North Carolina, Texas, and the Virgin Islands. In contrast, unique major proteins were observed in dog sera from Italy and Zimbabwe. Our results indicate that although relatively homogeneous, antigenic diversity may exist among E. canis organisms in different regions of the world.

The question whether influenza vaccine could lead to a clinical flare in patients with rheumatoid arthritis (RA), and whether it could induce an effectively protective antibody response to the infection is still much debated. Based on these data, we have performed an open study in 40 patients with RA. Patients were divided into two groups according to their disease activity (those with RA in remission and those with active RA, respectively), and their clinical and serum antibody response was assessed following the vaccine administration in the 1991-92 winter seasons. A group of age and sex matched, healthy controls were also vaccinated. Our results suggest that immunization against influenza does not modify the clinical picture of RA, even though some differences between the two groups mentioned above were noticed. In addition, side-effects or adverse reactions occurred with similar frequency in patients with RA and in the controls; as to the antibody response in patients with RA, in the majority of cases the immune response proved adequate to provide significant protection from the infection.

Serum humoral immunological parameters were determined in 25 patients with atrophic-erosive forms of oral lichen planus (OLP) (Group 1), in 28 patients with reticular-plaque-like lesions of OLP (Group 2) and in 21 healthy patients without oral lesions (Group 3). Comparing patients affected by atrophic-erosive forms of OLP (Group 1) with normal controls (Group 3), increased levels of serum IgG approaching the statistical significance were found (Kruskal-Wallis test p = 0.0572). It was also found a significantly higher value of kappa (Kruskal-Wallis test p = 0.0017; Mann-Whitney test with Bonferroni's correction p < 0.001) and lambda (Kruskal-Wallis test p = 0.0346; Mann-Whitney test with Bonferroni's correction p = 0.013) light chains in patients with atrophic-erosive OLP (Group 1) as compared with normal controls (Group 3). However these higher levels were probably caused by strong prevalence of chronic liver diseases (40%), in patients with atrophic-erosive variety of OLP. No one of these patients was affected by autoimmune liver disease. No differences were noted between atrophic-erosive OLP (Group 1) and hyperkeratotic OLP (Group 2). This study does not confirm the suggestion that patients with OLP may have a generalized immunologic disorder and it also add some evidences that the role of humoral immunity in the pathogenesis of OLP is probably secondary to the cell-mediated reaction against basal keratinocytes.

An epidemiological study was carried out on 114 beta-thalassaemics in order to select those subjects susceptible to hepatitis B virus (HBV) infection for hepatitis B vaccination. The results confirmed the high risk of HBV infection in these patients: 9.6% were HBsAg positive, 29.8% were anti-HBs positive/anti-HBc positive, and 9% were anti-HBc positive. In 60 HBV-negative patients, 20 micrograms doses of hepatitis B vaccine were administered on a schedule of 0, 1 and 6 months. Sera were collected for six years to determine the seroconversion rate and the anti-HBs titre. Seroconversion reached a maximum rate of 93% 12 months after the first vaccination dose and was 80% at the final control (72 months). Highly protective anti-HBs titres were observed until the last control in a high percentage of subjects. The HBVax hepatitis B vaccine has been shown to be safe, immunogenic and effective in beta-thalassaemics.

In order to verify the hypothesis that Italian patients with systemic lupus erythematosus (SLE) may be immunogenetically distinct from SLE patients born in other regions, we investigated the HLA class I and II antigens and their relation with the various autoantibodies characteristic of the disease in an Italian SLE population. Forty-four SLE patients were typed for HLA-A, -B, -C, -DR and -DQ antigens; sera from the same patients were tested for the presence of antibodies to the nuclear or cytoplasmic antigens Ro/SSA, La/SSB, Sm and RNP (ENA). Results of HLA typing showed that the frequencies of DR3 and DQw2 were increased in patients compared with controls. Analysis of the correlations between HLA antigens and anti-ENA antibodies showed that both DQw2 and DR3 were increased in patients with anti-Ro and/or antiLa antibodies, while in patients with anti-Sm and/or antiRNP antibodies the DQw2 and DR4 were found to be increased. Only DQw2 was found to be significantly increased in anti-ENA positive patients. These results might suggest that Italian patients with SLE are, at least in part, different from lupus patients living in other geographical areas and suggest the association of DQw2 with the autoantibody response to ENA in SLE.

A study on the prevalence of seropositivity to T.gondii, Rubella virus, Cytomegalovirus and Herpes simplex virus (type 1 and type 2) was carried out in pregnant women aged 15-45 years. An overall prevalence of 40.7% to T.gondii, of 90.1% to Rubella virus, of 80.8% to Cytomegalovirus, of 82.3% and of 69% to Herpes simplex virus, respectively type 1 and type 2 was found. Cytomegalovirus infection was prevalent in women from low socioeconomic background. Herpes simplex 1 infection was higher in women living in quarters of high density population, whereas antibody prevalence to Rubella virus was higher in women from high socioeconomic setting. The expected fetal risk for T.gondii, Rubella and Cytomegalovirus infections has been assessed on the basis of the yearly seroconversion rate for each pathogen in the study population and of the known transplacental transmission rates after primary and recurrent infection in pregnancy. Thus, the expected incidence of congenital T.gondii infection in this geographic area is 0.2-0.3%, of congenital Rubella infection of 0.02% and of congenital Cytomegalovirus infection of 0.3-1.15%.

A cross-sectional epidemiological study was carried out on 2932 farmers (response rate 92%) living in Northern Italy. A questionnaire on respiratory symptoms was supplied, chest X-ray taken and simple spirometry tests made. Thirty-nine subjects reported attacks of breathlessness associated with fever after exposure to mouldy hay; thirty-six had a clinical history of farmer's lung and X-ray and/or respiratory function changes indicative of chronic farmer's lung; 113 were classified as having bronchial asthma. These 118 subjects and a random sample of 131 non-symptomatic subjects were examined by intracutaneous skin tests and double diffusion precipitation tests with antigens associated with farmer's lung. All sera positive by precipitation were examined by immunoelectrophoresis, counterimmunoelectrophoresis, and C1q binding test, and Bovine conglutinin test in solid phase for the detection of circulating immunocomplexes. 27.8% cases of chronic farmer's lung, 4.4% of cases of bronchial asthma and 2.3% of non-symptomatic subjects showed precipitating antibodies against farmer's lung antigens. Of the precipitin-positive subjects, the majority had precipitating antibodies against Micropolyspora faeni. No differences in immunoelectrophoregrams in number and pattern of precipitation arcs for M. faeni were found between chronic farmer's lung and bronchial asthma subjects. Circulating immune complexes were present in 50% of chronic farmer's lung patients, 40% of those with bronchial asthma and 33.3% of non-symptomatic subjects. Three farmer's lung subjects (9.3%) showed immediate skin-test reactions to rural environmental allergens.

The Authors carried out a serological research on the polimyelitis viruses in 727 adult subjects who had not been vaccinated orally. The results of the titration of the neutralizing antibodies showed that the situation of immunity with respect to poliomyelitis is still satisfactory. However, the difficulty of making an exact estimation of the duration of the state of immunity to poliomyelitis, and the persistent, though reduced, circulation of wild polioviruses are such that a continuous epidemiological control is advisable.