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Congenital cytomegalovirus infection (cCMV) may affect about 1% of all newborns all over the world as a result of either a primary or recurrent human cytomegalovirus (HCMV) infection. While about 90% of infants affected by cCMV are asymptomatic at birth, the remaining 10% are symptomatic often with neurodevelopmental impairment and sensorineural hearing loss. In view of identifying the best approach to vaccine prevention of cCMV, this review will examine the most important steps made in the study of the immune response to, and diagnosis of, HCMV infection. The maternal immune response and immune correlates of protection are being partially identified with a partial contribution given by our laboratory. The diagnosis of primary infection is often difficult to achieve in the first three months of pregnancy, which is the time primarily involved in virus transmission to the fetus in association with the most severe symptoms and sequelae. Prevention of cCMV is anticipated by prevention of primary infection in early pregnancy by means of different measures, such as (i) behavioral-educational measures, (ii) immunoglobulin administration, (iii) antiviral treatment with valaciclovir. However, the most promising approach to cCMV prevention appears to be the development of a non-living vaccine, including at least three viral antigens: gB, pentamer complex gHgLpUL128L, and pp65, which have been shown to be able to stimulate both the humoral and the cellular arms of the maternal immune response. Primary HCMV infection may be managed in pregnancy by counseling of the couples involved by a team of specialists that includes virologists, obstetricians, infectivologists and neonatologists.
Giuseppe Gerna; Chiara Fornara; Milena Furione; Daniele Lilleri. Congenital Human Cytomegalovirus Infection: A Narrative Review of Maternal Immune Response and Diagnosis in View of the Development of a Vaccine and Prevention of Primary and Non-Primary Infections in Pregnancy. Microorganisms 2021, 9, 1749 .
AMA StyleGiuseppe Gerna, Chiara Fornara, Milena Furione, Daniele Lilleri. Congenital Human Cytomegalovirus Infection: A Narrative Review of Maternal Immune Response and Diagnosis in View of the Development of a Vaccine and Prevention of Primary and Non-Primary Infections in Pregnancy. Microorganisms. 2021; 9 (8):1749.
Chicago/Turabian StyleGiuseppe Gerna; Chiara Fornara; Milena Furione; Daniele Lilleri. 2021. "Congenital Human Cytomegalovirus Infection: A Narrative Review of Maternal Immune Response and Diagnosis in View of the Development of a Vaccine and Prevention of Primary and Non-Primary Infections in Pregnancy." Microorganisms 9, no. 8: 1749.
Solid organ transplant recipients, due to the administration of post-transplant immunosuppressive therapies, are at greater risk of viral reactivation episodes, mainly from herpes viruses, including varicella-zoster virus (VZV). The aim of this pilot study was to develop functional immunological assays (VZV-ELISpot) for the quantification and characterization of the VZV-specific effector-memory and central-memory responses in healthy subjects and transplanted patients. Glycoprotein gE and immediate-early 63 (IE-63) were used as antigens for in vitro stimulation. VZV-seropositive healthy subjects showed higher responses in respect to seronegative subjects. Even if differences were observed between VZV-seropositive healthy subjects and transplanted subjects at pre-transplant, the VZV-specific T-cell response was reduced at 60 days after transplant, mainly for the high level of immunosuppression. Phenotypical characterization revealed that response against VZV was mainly mediated by CD4 T cells. The results obtained in this study might be useful for the definition of personalized follow-up of the transplanted patients, providing useful information on the status of the patient potentially at risk of viral reactivation or other opportunistic infections.
Irene Cassaniti; Alessandro Ferrari; Giuditta Comolli; Antonella Sarasini; Marilena Gregorini; Teresa Rampino; Daniele Lilleri; Fausto Baldanti. Characterization of Varicella-Zoster (VZV) Specific T Cell Response in Healthy Subjects and Transplanted Patients by Using Enzyme Linked Immunospot (ELISpot) Assays. Vaccines 2021, 9, 875 .
AMA StyleIrene Cassaniti, Alessandro Ferrari, Giuditta Comolli, Antonella Sarasini, Marilena Gregorini, Teresa Rampino, Daniele Lilleri, Fausto Baldanti. Characterization of Varicella-Zoster (VZV) Specific T Cell Response in Healthy Subjects and Transplanted Patients by Using Enzyme Linked Immunospot (ELISpot) Assays. Vaccines. 2021; 9 (8):875.
Chicago/Turabian StyleIrene Cassaniti; Alessandro Ferrari; Giuditta Comolli; Antonella Sarasini; Marilena Gregorini; Teresa Rampino; Daniele Lilleri; Fausto Baldanti. 2021. "Characterization of Varicella-Zoster (VZV) Specific T Cell Response in Healthy Subjects and Transplanted Patients by Using Enzyme Linked Immunospot (ELISpot) Assays." Vaccines 9, no. 8: 875.
Objective The protection form SARS-CoV-2 infection induced by SARS-CoV-2 anti-S1 and anti-S2 IgG antibody positivity resulting from natural infection was evaluated. Methods The frequency of SARS-CoV-2 infection (as determined by virus RNA detection) was evaluated in a group of 1,460 seropositive and a control groups of 8,150 seronegative healthcare workers in three Centres of Northern Italy in the period June-November 2020. Neutralizing serum titers were analysed in seropositive subjects with or without secondary SARS-CoV-2 infection. Results During the 6-month survey, 1.78% seropositive subjects developed secondary SARS-CoV-2 infection while 6.63% seronegative controls developed primary infection (odds ratio: 0.26; 95% confidence interval: 0.17-0.38). Secondary infection was associated with low or absent serum neutralizing titer (p<0.01) and was mildly symptomatic in 45.8% cases vs 71.4% symptomatic primary infections (odds ratio: 0.34; 95% confidence interval: 0.16-0.78). Conclusions Immunity from natural infection appears protective from secondary infection; therefore, vaccination of seronegative subjects might be prioritized.
Francesca Rovida; Irene Cassaniti; Elena Percivalle; Antonella Sarasini; Stefania Paolucci; Catherine Klersy; Sara Cutti; Viola Novelli; Carlo Marena; Francesco Luzzaro; Giovanni De Vito; Roberta Schiavo; Giuliana Lo Cascio; Daniele Lilleri; Fausto Baldanti. Incidence of SARS-CoV-2 infection in health care workers from Northern Italy based on antibody status: immune protection from secondary infection- A retrospective observational case-controlled study. International Journal of Infectious Diseases 2021, 109, 199 -202.
AMA StyleFrancesca Rovida, Irene Cassaniti, Elena Percivalle, Antonella Sarasini, Stefania Paolucci, Catherine Klersy, Sara Cutti, Viola Novelli, Carlo Marena, Francesco Luzzaro, Giovanni De Vito, Roberta Schiavo, Giuliana Lo Cascio, Daniele Lilleri, Fausto Baldanti. Incidence of SARS-CoV-2 infection in health care workers from Northern Italy based on antibody status: immune protection from secondary infection- A retrospective observational case-controlled study. International Journal of Infectious Diseases. 2021; 109 ():199-202.
Chicago/Turabian StyleFrancesca Rovida; Irene Cassaniti; Elena Percivalle; Antonella Sarasini; Stefania Paolucci; Catherine Klersy; Sara Cutti; Viola Novelli; Carlo Marena; Francesco Luzzaro; Giovanni De Vito; Roberta Schiavo; Giuliana Lo Cascio; Daniele Lilleri; Fausto Baldanti. 2021. "Incidence of SARS-CoV-2 infection in health care workers from Northern Italy based on antibody status: immune protection from secondary infection- A retrospective observational case-controlled study." International Journal of Infectious Diseases 109, no. : 199-202.
Vaccine breakthrough SARS-CoV-2 infection was monitored in 3694 healthcare workers receiving 2 doses of BNT162b2. SARS-CoV2 infection was detected in 33 subjects, with a 3-months cumulative incidence of 0.90% and 0.42% in SARS-CoV-2-naive and experienced subjects, respectively. Vaccine protection was 87% in naive and 94% in experienced subjects when compared with a pre-vaccination control group. The infection was mildly symptomatic in 16 (48%) and asymptomatic in 17 (52%) subjects. Virus isolation was positive in 7/13 (54%) symptomatic and 4/8 (50%) asymptomatic subjects tested, and B.1.1.7 lineage was detected in all subjects. Antibody and T-cell responses were not reduced in subjects with breakthrough infection. Evidence of virus transmission, determined by contact tracing, was observed in two (6.1%) cases. This real-world data confirm the protective effect of the BNT162b2 vaccine. A triple antigenic exposure, as occurring in experienced subjects, may confer higher protection. Virus transmission from vaccinated subjects is infrequent.
Francesca Rovida; Irene Cassaniti; Stefania Paolucci; Elena Percivalle; Antonella Sarasini; Antonio Piralla; Federica Giardina; Jose Camilla Sammartino; Alessandro Ferrari; Federica Bergami; Alba Muzzi; Viola Novelli; Alessandro Meloni; Anna Maria Grugnetti; Giuseppina Grugnetti; Claudia Rona; Marinella Daglio; Carlo Marena; Antonio Triarico; Daniele Lilleri; Fausto Baldanti. SARS-CoV-2 vaccine breakthrough infections are asymptomatic or mildly symptomatic and are infrequently transmitted. 2021, 1 .
AMA StyleFrancesca Rovida, Irene Cassaniti, Stefania Paolucci, Elena Percivalle, Antonella Sarasini, Antonio Piralla, Federica Giardina, Jose Camilla Sammartino, Alessandro Ferrari, Federica Bergami, Alba Muzzi, Viola Novelli, Alessandro Meloni, Anna Maria Grugnetti, Giuseppina Grugnetti, Claudia Rona, Marinella Daglio, Carlo Marena, Antonio Triarico, Daniele Lilleri, Fausto Baldanti. SARS-CoV-2 vaccine breakthrough infections are asymptomatic or mildly symptomatic and are infrequently transmitted. . 2021; ():1.
Chicago/Turabian StyleFrancesca Rovida; Irene Cassaniti; Stefania Paolucci; Elena Percivalle; Antonella Sarasini; Antonio Piralla; Federica Giardina; Jose Camilla Sammartino; Alessandro Ferrari; Federica Bergami; Alba Muzzi; Viola Novelli; Alessandro Meloni; Anna Maria Grugnetti; Giuseppina Grugnetti; Claudia Rona; Marinella Daglio; Carlo Marena; Antonio Triarico; Daniele Lilleri; Fausto Baldanti. 2021. "SARS-CoV-2 vaccine breakthrough infections are asymptomatic or mildly symptomatic and are infrequently transmitted." , no. : 1.
BNT162b2 vaccine was introduced in Italy on 27th December 2020 and healthcare workers were rapidly vaccinated. In this study, we demonstrated that one vaccine dose was sufficient for eliciting a sustained humoral and cell-mediated response in SARS-CoV-2 experienced healthcare workers but had a lower effect in SARS-CoV-2 naïve subjects. However, 98% naïve subjects developed both neutralizing antibodies and Spike-specific T-cells after the second dose. Moreover, the antibody and T-cell responses were effective against viral variants since a partial reduction in antibody response was observed only against the South-African variant in SARS-CoV-2 naïve individuals, while the T-cell response was less affected.
Daniele Lilleri; Irene Cassaniti; Federica Bergami; Elena Percivalle; Elisa Gabanti; Josè Camilla Sammartino; Alessandro Ferrari; Kodjo Adzasehoun; Federica Zavaglio; Paola Zelini; Giuditta Comolli; Antonella Sarasini; Antonio Piralla; Alessandra Ricciardi; Valentina Zuccaro; Fabrizio Maggi; Federica Novazzi; Luca Simonelli; Luca Varani; Fausto Baldanti. SARS-CoV-2 mRNA vaccine BNT162b2 elicited a robust humoral and cellular response against SARS-CoV-2 variants. 2021, 1 .
AMA StyleDaniele Lilleri, Irene Cassaniti, Federica Bergami, Elena Percivalle, Elisa Gabanti, Josè Camilla Sammartino, Alessandro Ferrari, Kodjo Adzasehoun, Federica Zavaglio, Paola Zelini, Giuditta Comolli, Antonella Sarasini, Antonio Piralla, Alessandra Ricciardi, Valentina Zuccaro, Fabrizio Maggi, Federica Novazzi, Luca Simonelli, Luca Varani, Fausto Baldanti. SARS-CoV-2 mRNA vaccine BNT162b2 elicited a robust humoral and cellular response against SARS-CoV-2 variants. . 2021; ():1.
Chicago/Turabian StyleDaniele Lilleri; Irene Cassaniti; Federica Bergami; Elena Percivalle; Elisa Gabanti; Josè Camilla Sammartino; Alessandro Ferrari; Kodjo Adzasehoun; Federica Zavaglio; Paola Zelini; Giuditta Comolli; Antonella Sarasini; Antonio Piralla; Alessandra Ricciardi; Valentina Zuccaro; Fabrizio Maggi; Federica Novazzi; Luca Simonelli; Luca Varani; Fausto Baldanti. 2021. "SARS-CoV-2 mRNA vaccine BNT162b2 elicited a robust humoral and cellular response against SARS-CoV-2 variants." , no. : 1.
Background: Strain-specific antibodies to human cytomegalovirus (HCMV) glycoproteins B and H (gB and gH) have been proposed as a potential diagnostic tool for identifying reinfection. We investigated genotype-specific IgG antibody responses in parallel with defining the gB and gH genotypes of the infecting viral strains. Methods: Subjects with primary (n = 20) or non-primary (n = 25) HCMV infection were studied. The seven gB (gB1-7) and two gH (gH1-2) genotypes were determined by real-time PCR and whole viral genome sequencing, and genotype-specific IgG antibodies were measured by a peptide-based enzyme-linked immunosorbent assay (ELISA). Results: Among subjects with primary infection, 73% (n = 8) infected by gB1-HCMV and 63% (n = 5) infected by gB2/3-HCMV had genotype-specific IgG antibodies to gB (gB2 and gB3 are similar in the region tested). Peptides from the rarer gB4-gB7 genotypes had nonspecific antibody responses. All subjects infected by gH1-HCMV and 86% (n = 6) infected by gH2-HCMV developed genotype-specific responses. Among women with non-primary infection, gB and gH genotype-specific IgG antibodies were detected in 40% (n = 10) and 80% (n = 20) of subjects, respectively. Conclusions: Peptide-based ELISA is capable of detecting primary genotype-specific IgG responses to HCMV gB and gH, and could be adopted for identifying reinfections. However, about half of the subjects did not have genotype-specific IgG antibodies to gB.
Federica Zavaglio; Loretta Fiorina; Nicolás Suárez; Chiara Fornara; Marica De Cicco; Daniela Cirasola; Andrew Davison; Giuseppe Gerna; Daniele Lilleri. Detection of Genotype-Specific Antibody Responses to Glycoproteins B and H in Primary and Non-Primary Human Cytomegalovirus Infections by Peptide-Based ELISA. Viruses 2021, 13, 399 .
AMA StyleFederica Zavaglio, Loretta Fiorina, Nicolás Suárez, Chiara Fornara, Marica De Cicco, Daniela Cirasola, Andrew Davison, Giuseppe Gerna, Daniele Lilleri. Detection of Genotype-Specific Antibody Responses to Glycoproteins B and H in Primary and Non-Primary Human Cytomegalovirus Infections by Peptide-Based ELISA. Viruses. 2021; 13 (3):399.
Chicago/Turabian StyleFederica Zavaglio; Loretta Fiorina; Nicolás Suárez; Chiara Fornara; Marica De Cicco; Daniela Cirasola; Andrew Davison; Giuseppe Gerna; Daniele Lilleri. 2021. "Detection of Genotype-Specific Antibody Responses to Glycoproteins B and H in Primary and Non-Primary Human Cytomegalovirus Infections by Peptide-Based ELISA." Viruses 13, no. 3: 399.
Primary infection occurs when seronegative women are infected by human cytomegalovirus (HCMV). Diagnosis of primary infection is based on the following: antibody seroconversion, presence of IgM and low IgG avidity index (AI), and presence of DNAemia. The kinetics of HCMV-specific IgM antibody and maturation of AI might be very rapid or long-lasting during primary infection, which makes serological diagnosis insidious. The aims of this study were as follows: (i) to report atypical kinetics of HCMV-specific IgM antibody and AI early after onset of primary HCMV infection in a population of pregnant women, and (ii) to assess the frequency of such results. Altogether, 1309 sequential serum samples collected from 465 pregnant women with primary HCMV infection were included in the study. As a general rule, using the LIAISON®CMVIgMII and LIAISON®CMVIgGAvidityII assays, virus-specific IgM antibody levels decreased, while IgG AI increased over time during the first three months after infection onset. However, early clearance of IgM antibody and/or early IgG AI maturation occurred in 46/426 (10.7%) women. In more details, 20/426 (4.7%) and 26/418 (6.2%) women had undetectable IgM antibody or high IgG AI, respectively, when tested within 1–3 months after well-defined infection onset. Twenty sera from as many women with high IgG AI by the LIAISON assay were further tested for IgG AI by VIDAS®CMVIgGAvidityII and Mikrogen recomLineCMVIgG Avidity assays. Comparable results were obtained with VIDAS, whereas 14/20 sera gave low AI with the Mikrogen assay. In conclusion, about 11% of pregnant women undergoing a primary HCMV infection showed misleading serological results. Additional and appropriate testing might help in reducing the risk of missing HCMV primary infection in pregnancy. Furthermore, preconceptional testing should be strongly recommended.
Antonella Sarasini; Alessia Arossa; Maurizio Zavattoni; Chiara Fornara; Daniele Lilleri; Arsenio Spinillo; Fausto Baldanti; Milena Furione. Pitfalls in the Serological Diagnosis of Primary Human Cytomegalovirus Infection in Pregnancy Due to Different Kinetics of IgM Clearance and IgG Avidity Index Maturation. Diagnostics 2021, 11, 396 .
AMA StyleAntonella Sarasini, Alessia Arossa, Maurizio Zavattoni, Chiara Fornara, Daniele Lilleri, Arsenio Spinillo, Fausto Baldanti, Milena Furione. Pitfalls in the Serological Diagnosis of Primary Human Cytomegalovirus Infection in Pregnancy Due to Different Kinetics of IgM Clearance and IgG Avidity Index Maturation. Diagnostics. 2021; 11 (3):396.
Chicago/Turabian StyleAntonella Sarasini; Alessia Arossa; Maurizio Zavattoni; Chiara Fornara; Daniele Lilleri; Arsenio Spinillo; Fausto Baldanti; Milena Furione. 2021. "Pitfalls in the Serological Diagnosis of Primary Human Cytomegalovirus Infection in Pregnancy Due to Different Kinetics of IgM Clearance and IgG Avidity Index Maturation." Diagnostics 11, no. 3: 396.
Daniele Lilleri; Chiara Fornara. Detection of the potentiality before the actuality: Measurement of T‐cell proliferation before cell division occurs. Cytometry Part A 2021, 1 .
AMA StyleDaniele Lilleri, Chiara Fornara. Detection of the potentiality before the actuality: Measurement of T‐cell proliferation before cell division occurs. Cytometry Part A. 2021; ():1.
Chicago/Turabian StyleDaniele Lilleri; Chiara Fornara. 2021. "Detection of the potentiality before the actuality: Measurement of T‐cell proliferation before cell division occurs." Cytometry Part A , no. : 1.
Human cytomegalovirus (HCMV) infection is one of the major causes of mortality and morbidity after allo-hematopoietic stem cell transplantation (HSCT). Antiviral therapies are associated with toxicity and high economic burden. The aim of this retrospective study was to identify allo-HSCT HCMV-seropositive recipients at low risk of clinically significant HCMV infection who could avoid antiviral therapies. Sixty adult patients who underwent allo-HSCT were clustered in two groups: i) 22 (37%) spontaneously controlling HCMV reactivation (Controllers); ii) 38 (63%) developing clinically significant HCMV infection and receiving pre-emptive therapy (Non-Controllers). We analyzed several patient baseline characteristics, total/HCMV-specific CD4+ and CD8+ T-cell counts and their cytokine production (IFNγ, TNFα, IL2). Controllers presented a higher number of total/HCMV-specific CD4+ and CD8+ T-cells (P=0.001 and P=0.017 for total CD4+ and CD8+ T-cells respectively; P<0.001 for HCMV-specific T-cells) and a lower percentage of mono-functional IFNγ-producing HCMV-specific CD8+ T-cells (P=0.002). In bi-variable models, the prognostic impact of the percentage of mono-functional HCMV-specific CD8+ T-cells on treatment-free survival, adjusted for total/HCMVspecific CD4+ and CD8+ T-cells, was confirmed. An HCMV-seronegative donor was the only baseline characteristic associated with a clinically significant infection. These data, when confirmed by a larger prospective study, may provide information for guiding the personalized management of HCMV infection in allo-HSCT recipients.
Elisa Gabanti; Oscar Borsani; Daniela Caldera; Anna Amelia Colombo; Virginia Valeria Ferretti; Emilio Paolo Alessandrino; Giuseppe Gerna; Paolo Bernasconi; Daniele Lilleri. Early T cell reconstitution and cytokine profile may help to guide a personalized management of human cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation. Journal of Clinical Virology 2021, 135, 104734 .
AMA StyleElisa Gabanti, Oscar Borsani, Daniela Caldera, Anna Amelia Colombo, Virginia Valeria Ferretti, Emilio Paolo Alessandrino, Giuseppe Gerna, Paolo Bernasconi, Daniele Lilleri. Early T cell reconstitution and cytokine profile may help to guide a personalized management of human cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation. Journal of Clinical Virology. 2021; 135 ():104734.
Chicago/Turabian StyleElisa Gabanti; Oscar Borsani; Daniela Caldera; Anna Amelia Colombo; Virginia Valeria Ferretti; Emilio Paolo Alessandrino; Giuseppe Gerna; Paolo Bernasconi; Daniele Lilleri. 2021. "Early T cell reconstitution and cytokine profile may help to guide a personalized management of human cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation." Journal of Clinical Virology 135, no. : 104734.
Containment measures have been applied in several countries in order to limit the diffusion of the SARS-CoV-2 epidemic. The scope of this study is to analyze the evolution of the first wave of the SARS-CoV-2 epidemic throughout Italy and factors associated to the different way it spread in the Italian Regions, starting from the day that the first indigenous cases were detected through day 81 (6 days after the end of the strict lockdown). Data were obtained from daily reports and are represented as number (and percentage) of cases/100,000 persons. A lockdown with movement restrictions, especially across Regions, was declared at day 20. At day 81, 219,070 cases (363/100,000 persons) were diagnosed. A regression analysis based on the Gompertz model predicts a total number 233,606 cases (386/100,000 persons) at the end of the epidemic. The 21 areas, divided into Italian Regions and autonomous Provinces, showed a wide range in the frequency of cases at day 81 (58–921, median 258/100,000 persons) and total predicted cases (58–946, median 267/100,000 persons). Similarly, the predicted time for the end of the wave of the epidemic (considering as surrogate marker the time at which 99% of the total cases are predicted to occur) was highly variable, ranging from 64 to 136 (median 99) days. We analyzed the impact of local and interventional variables on the epidemic curve in each Region. The number of cases correlated inversely with the distance from the area in which first cases were detected and directly also with the gross domestic product pro capite (as a marker of industrial activity) of the Region. Moreover, an earlier start of the lockdown (i.e. in the presence of a lower number of cases) and wider testing were associated with a lower final number of total cases. In conclusion, this analysis shows that population-wide testing and early lockdown enforcement appear effective in limiting the spreading of the SARS-CoV-2 epidemic.
Daniele Lilleri; Federica Zavaglio; Elisa Gabanti; Giuseppe Gerna; Eloisa Arbustini. Analysis of the SARS-CoV-2 epidemic in Italy: The role of local and interventional factors in the control of the epidemic. PLOS ONE 2020, 15, e0242305 .
AMA StyleDaniele Lilleri, Federica Zavaglio, Elisa Gabanti, Giuseppe Gerna, Eloisa Arbustini. Analysis of the SARS-CoV-2 epidemic in Italy: The role of local and interventional factors in the control of the epidemic. PLOS ONE. 2020; 15 (11):e0242305.
Chicago/Turabian StyleDaniele Lilleri; Federica Zavaglio; Elisa Gabanti; Giuseppe Gerna; Eloisa Arbustini. 2020. "Analysis of the SARS-CoV-2 epidemic in Italy: The role of local and interventional factors in the control of the epidemic." PLOS ONE 15, no. 11: e0242305.
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Chiara Fornara; Milena Furione; Federica Zavaglio; Alessia Arossa; Arsenio Spinillo; Giuseppe Gerna; Daniele Lilleri. Slow cytomegalovirus‐specific CD4 + and CD8 + T‐cell differentiation: 10‐year follow‐up of primary infection in a small number of immunocompetent hosts. European Journal of Immunology 2020, 51, 253 -256.
AMA StyleChiara Fornara, Milena Furione, Federica Zavaglio, Alessia Arossa, Arsenio Spinillo, Giuseppe Gerna, Daniele Lilleri. Slow cytomegalovirus‐specific CD4 + and CD8 + T‐cell differentiation: 10‐year follow‐up of primary infection in a small number of immunocompetent hosts. European Journal of Immunology. 2020; 51 (1):253-256.
Chicago/Turabian StyleChiara Fornara; Milena Furione; Federica Zavaglio; Alessia Arossa; Arsenio Spinillo; Giuseppe Gerna; Daniele Lilleri. 2020. "Slow cytomegalovirus‐specific CD4 + and CD8 + T‐cell differentiation: 10‐year follow‐up of primary infection in a small number of immunocompetent hosts." European Journal of Immunology 51, no. 1: 253-256.
Human cytomegalovirus (HCMV) is the leading infectious agent causing congenital disabilities. The risk of HCMV transmission to the fetus in pregnant women receiving immunosuppressive agents is unknown. We describe two cases of pregnant women with evidence of pre-conception HCMV protective immunity receiving azathioprine for ulcerative colitis or systemic lupus erythematosus. Both women reactivated the HCMV and transmitted the infection to the fetuses. One newborn showed unilateral hearing deficits and brain abnormalities while the other was asymptomatic. The mother of the symptomatic newborn had low levels of total and HCMV-specific blood CD4+ T cells. Women receiving immunosuppressive agents deserve information about the risk of HCMV congenital infection and should be monitored for HCMV infection during pregnancy. Their newborns should be screened for HCMV congenital infection.
Paolo Ivo Cavoretto; Chiara Fornara; Cristina Baldoli; Alessia Arossa; Milena Furione; Massimo Candiani; Patrizia Rovere Querini; Graziano Barera; Antonella Poloniato; Gerarda Gaeta; Arsenio Spinillo; Daniele Lilleri. Prenatal Management of Congenital Human Cytomegalovirus Infection in Seropositive Pregnant Patients Treated with Azathioprine. Diagnostics 2020, 10, 542 .
AMA StylePaolo Ivo Cavoretto, Chiara Fornara, Cristina Baldoli, Alessia Arossa, Milena Furione, Massimo Candiani, Patrizia Rovere Querini, Graziano Barera, Antonella Poloniato, Gerarda Gaeta, Arsenio Spinillo, Daniele Lilleri. Prenatal Management of Congenital Human Cytomegalovirus Infection in Seropositive Pregnant Patients Treated with Azathioprine. Diagnostics. 2020; 10 (8):542.
Chicago/Turabian StylePaolo Ivo Cavoretto; Chiara Fornara; Cristina Baldoli; Alessia Arossa; Milena Furione; Massimo Candiani; Patrizia Rovere Querini; Graziano Barera; Antonella Poloniato; Gerarda Gaeta; Arsenio Spinillo; Daniele Lilleri. 2020. "Prenatal Management of Congenital Human Cytomegalovirus Infection in Seropositive Pregnant Patients Treated with Azathioprine." Diagnostics 10, no. 8: 542.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly reached pandemic proportions. We conducted a prospective study to assess deep lung inflammatory status in patients with moderate to severe COVID-19.Diagnostic bronchoalveolar lavage (BAL) was performed in 33 adult patients with SARS-CoV-2 infection by real-time PCR on nasopharyngeal swab admitted to the Intensive care unit (ICU) (n=28) and to the Intermediate Medicine Ward (IMW) (n=5). We analyze the differential cell count, ultrastructure of cells and Interleukin(IL)6, 8 and 10 levels.ICU patients showed a marked increase in neutrophils (72%, 60-81), lower lymphocyte (8%, 4-12) and macrophages fractions (17%, 11-27) compared to IMW patients (3%, 2-17, 15%, 6-26 and 74%, 58-90, respectively) (pvs. survivors). IL10 did not show a significant variation between groups. Dividing patients by treatment received, lower BAL concentrations of IL6 were found in patients treated with steroids as compared to those treated with tocilizumab (pAlveolitis, associated with COVID-19, is mainly sustained by innate effectors which showed features of extensive activation. The burden of pro-inflammatory cytokines IL6 and IL8 in the broncho-alveolar environment is associated with clinical outcome.
Laura Pandolfi; Tommaso Fossali; Vanessa Frangipane; Sara Bozzini; Monica Morosini; Maura D’Amato; Sara Lettieri; Mario Urtis; Alessandro Di Toro; Laura Saracino; Elena Percivalle; Stefano Tomaselli; Lorenzo Cavagna; Emanuela Cova; Francesco Mojoli; Paola Bergomi; Davide Ottolina; Daniele Lilleri; Angelo Guido Corsico; Eloisa Arbustini; Riccardo Colombo; Federica Meloni. Broncho-alveolar inflammation in COVID-19 patients: a correlation with clinical outcome. 2020, 1 .
AMA StyleLaura Pandolfi, Tommaso Fossali, Vanessa Frangipane, Sara Bozzini, Monica Morosini, Maura D’Amato, Sara Lettieri, Mario Urtis, Alessandro Di Toro, Laura Saracino, Elena Percivalle, Stefano Tomaselli, Lorenzo Cavagna, Emanuela Cova, Francesco Mojoli, Paola Bergomi, Davide Ottolina, Daniele Lilleri, Angelo Guido Corsico, Eloisa Arbustini, Riccardo Colombo, Federica Meloni. Broncho-alveolar inflammation in COVID-19 patients: a correlation with clinical outcome. . 2020; ():1.
Chicago/Turabian StyleLaura Pandolfi; Tommaso Fossali; Vanessa Frangipane; Sara Bozzini; Monica Morosini; Maura D’Amato; Sara Lettieri; Mario Urtis; Alessandro Di Toro; Laura Saracino; Elena Percivalle; Stefano Tomaselli; Lorenzo Cavagna; Emanuela Cova; Francesco Mojoli; Paola Bergomi; Davide Ottolina; Daniele Lilleri; Angelo Guido Corsico; Eloisa Arbustini; Riccardo Colombo; Federica Meloni. 2020. "Broncho-alveolar inflammation in COVID-19 patients: a correlation with clinical outcome." , no. : 1.
Congenital cytomegalovirus (cCMV) might occur as a result of the human cytomegalovirus (HCMV) primary (PI) or nonprimary infection (NPI) in pregnant women. Immune correlates of protection against cCMV have been partly identified only for PI. Following either PI or NPI, HCMV strains undergo latency. From a diagnostic standpoint, while the serological criteria for the diagnosis of PI are well-established, those for the diagnosis of NPI are still incomplete. Thus far, a recombinant gB subunit vaccine has provided the best results in terms of partial protection. This partial efficacy was hypothetically attributed to the post-fusion instead of the pre-fusion conformation of the gB present in the vaccine. Future efforts should be addressed to verify whether a new recombinant gB pre-fusion vaccine would provide better results in terms of prevention of both PI and NPI. It is still a matter of debate whether human hyperimmune globulin are able to protect from HCMV vertical transmission. In conclusion, the development of an HCMV vaccine that would prevent a significant portion of PI would be a major step forward in the development of a vaccine for both PI and NPI.
Giuseppe Gerna; Daniele Lilleri. Human Cytomegalovirus Congenital (cCMV) Infection Following Primary and Nonprimary Maternal Infection: Perspectives of Prevention through Vaccine Development. Vaccines 2020, 8, 194 .
AMA StyleGiuseppe Gerna, Daniele Lilleri. Human Cytomegalovirus Congenital (cCMV) Infection Following Primary and Nonprimary Maternal Infection: Perspectives of Prevention through Vaccine Development. Vaccines. 2020; 8 (2):194.
Chicago/Turabian StyleGiuseppe Gerna; Daniele Lilleri. 2020. "Human Cytomegalovirus Congenital (cCMV) Infection Following Primary and Nonprimary Maternal Infection: Perspectives of Prevention through Vaccine Development." Vaccines 8, no. 2: 194.
IgM and IgG avidity are not always reliable for diagnosis of primary HCMV infections. Anti-p52 IgM and anti-gB IgG provide additional tools in dating HCMV infections. Combination of different assays improves diagnosis and dating of HCMV infections.
Paola Zelini; Chiara Fornara; Milena Furione; Antonella Sarasini; Julia Klemens; Alessia Arossa; Arsenio Spinillo; Giuseppe Gerna; Daniele Lilleri. Determination of anti-p52 IgM and anti-gB IgG by ELISA as a novel diagnostic tool for detection of early and late phase of primary human cytomegalovirus infections during pregnancy. Journal of Clinical Virology 2019, 120, 38 -43.
AMA StylePaola Zelini, Chiara Fornara, Milena Furione, Antonella Sarasini, Julia Klemens, Alessia Arossa, Arsenio Spinillo, Giuseppe Gerna, Daniele Lilleri. Determination of anti-p52 IgM and anti-gB IgG by ELISA as a novel diagnostic tool for detection of early and late phase of primary human cytomegalovirus infections during pregnancy. Journal of Clinical Virology. 2019; 120 ():38-43.
Chicago/Turabian StylePaola Zelini; Chiara Fornara; Milena Furione; Antonella Sarasini; Julia Klemens; Alessia Arossa; Arsenio Spinillo; Giuseppe Gerna; Daniele Lilleri. 2019. "Determination of anti-p52 IgM and anti-gB IgG by ELISA as a novel diagnostic tool for detection of early and late phase of primary human cytomegalovirus infections during pregnancy." Journal of Clinical Virology 120, no. : 38-43.
In the 1970s–1980s, a striking increase in the number of disseminated human cytomegalovirus (HCMV) infections occurred in immunosuppressed patient populations. Autopsy findings documented the in vivo disseminated infection (besides fibroblasts) of epithelial cells, endothelial cells, and polymorphonuclear leukocytes. As a result, multiple diagnostic assays, such as quantification of HCMV antigenemia (pp65), viremia (infectious virus), and DNAemia (HCMV DNA) in patient blood, were developed. In vitro experiments showed that only low passage or endothelial cell-passaged clinical isolates, and not laboratory-adapted strains, could reproduce both HCMV leuko- and endothelial cell-tropism, which were found through genetic analysis to require the three viral genes UL128, UL130, and UL131 of the HCMV UL128 locus (UL128L). Products of this locus, together with gH/gL, were shown to form the gH/gL/pUL128L pentamer complex (PC) required for infection of epithelial cells/endothelial cells, whereas gH/gL and gO form the gH/gL/gO trimer complex (TC) required for infection of all cell types. In 2016, following previous work, a receptor for the TC that mediates entry into fibroblasts was identified as PDGFRα, while in 2018, a receptor for the PC that mediates entry into endothelial/epithelial cells was identified as neuropilin2 (Nrp2). Furthermore, the olfactory receptor family member OR14I1 was recently identified as a possible additional receptor for the PC in epithelial cells. Thus, current data support two models of viral entry: (i) in fibroblasts, following interaction of PDGFRα with TC, the latter activates gB to fuse the virus envelope with the cell membrane, whereas (ii) in epithelial cells/endothelial cells, interaction of Nrp2 (and OR14I1) with PC promotes endocytosis of virus particles, followed by gB activation by gH/gL/gO (or gH/gL) and final low-pH entry into the cell.
Giuseppe Gerna; Anna Kabanova; Daniele Lilleri. Human Cytomegalovirus Cell Tropism and Host Cell Receptors. Vaccines 2019, 7, 70 .
AMA StyleGiuseppe Gerna, Anna Kabanova, Daniele Lilleri. Human Cytomegalovirus Cell Tropism and Host Cell Receptors. Vaccines. 2019; 7 (3):70.
Chicago/Turabian StyleGiuseppe Gerna; Anna Kabanova; Daniele Lilleri. 2019. "Human Cytomegalovirus Cell Tropism and Host Cell Receptors." Vaccines 7, no. 3: 70.
Giuseppe Gerna; Daniele Lilleri. Human cytomegalovirus (HCMV) infection/re-infection: development of a protective HCMV vaccine. The new microbiologica 2019, 42, 1 -20.
AMA StyleGiuseppe Gerna, Daniele Lilleri. Human cytomegalovirus (HCMV) infection/re-infection: development of a protective HCMV vaccine. The new microbiologica. 2019; 42 (1):1-20.
Chicago/Turabian StyleGiuseppe Gerna; Daniele Lilleri. 2019. "Human cytomegalovirus (HCMV) infection/re-infection: development of a protective HCMV vaccine." The new microbiologica 42, no. 1: 1-20.
The genomic characteristics of human cytomegalovirus (HCMV) strains sequenced directly from clinical pathology samples were investigated, focusing on variation, multiple-strain infection, recombination and natural mutation. A total of 207 datasets generated in this and previous studies using target enrichment and high-throughput sequencing were analysed, in the process facilitating the determination of genome sequences for 91 strains. Key findings were that (i) it is important to monitor the quality of sequencing libraries in investigating diversity, (ii) many recombinant strains have been transmitted during HCMV evolution, and some have apparently survived for thousands of years without further recombination, (iii) mutants with non-functional genes (pseudogenes) have been circulating and recombining for long periods and can cause congenital infection and resulting clinical sequelae, and (iv) intrahost diversity in single-strain infections is much less than that in multiple-strain infections. Future population-based studies are likely to continue illuminating the evolution, epidemiology and pathogenesis of HCMV.
Nicolás M. Suárez; Gavin S. Wilkie; Elias Hage; Salvatore Camiolo; Marylouisa Holton; Joseph Hughes; Maha Maabar; Vattipally B. Sreenu; Akshay Dhingra; Ursula A. Gompels; Gavin W. G. Wilkinson; Fausto Baldanti; Milena Furione; Daniele Lilleri; Alessia Arossa; Tina Ganzenmueller; Giuseppe Gerna; Petr Hubacek; Thomas F. Schulz; Dana Wolf; Maurizio Zavattoni; Andrew J. Davison; Furione Milena. Human Cytomegalovirus Genomes Sequenced Directly from Clinical Material: Variation, Multiple-Strain Infection, Recombination and Mutation. 2018, 505735 .
AMA StyleNicolás M. Suárez, Gavin S. Wilkie, Elias Hage, Salvatore Camiolo, Marylouisa Holton, Joseph Hughes, Maha Maabar, Vattipally B. Sreenu, Akshay Dhingra, Ursula A. Gompels, Gavin W. G. Wilkinson, Fausto Baldanti, Milena Furione, Daniele Lilleri, Alessia Arossa, Tina Ganzenmueller, Giuseppe Gerna, Petr Hubacek, Thomas F. Schulz, Dana Wolf, Maurizio Zavattoni, Andrew J. Davison, Furione Milena. Human Cytomegalovirus Genomes Sequenced Directly from Clinical Material: Variation, Multiple-Strain Infection, Recombination and Mutation. . 2018; ():505735.
Chicago/Turabian StyleNicolás M. Suárez; Gavin S. Wilkie; Elias Hage; Salvatore Camiolo; Marylouisa Holton; Joseph Hughes; Maha Maabar; Vattipally B. Sreenu; Akshay Dhingra; Ursula A. Gompels; Gavin W. G. Wilkinson; Fausto Baldanti; Milena Furione; Daniele Lilleri; Alessia Arossa; Tina Ganzenmueller; Giuseppe Gerna; Petr Hubacek; Thomas F. Schulz; Dana Wolf; Maurizio Zavattoni; Andrew J. Davison; Furione Milena. 2018. "Human Cytomegalovirus Genomes Sequenced Directly from Clinical Material: Variation, Multiple-Strain Infection, Recombination and Mutation." , no. : 505735.
Immune correlates of protection against human cytomegalovirus (HCMV) infection are still debated. This study aimed to investigate which arm of the immune response plays a major role in protection against HCMV infection in kidney (KTR, n=40) and heart transplant recipients (HTR, n= 12). Overall, patients were divided into two groups: one including 37 patients with low viral load (LVL), and the other including 15 patients with high viral load (HVL). All LVL patients resolved the infection spontaneously, whereas HVL patients were all treated with one or more courses of antivirals. In HVL patients, viral DNAemia, which was more than 100 times higher than LVL, appeared and peaked at significantly earlier times, but disappeared much later than in LVL patients. During a 1‐year follow‐up, all LVL patients had levels of HCMV‐specific CD4+ (and CD8+) T‐cells significantly higher than HVL patients. On the contrary, titers of neutralizing antibodies, and ELISA‐IgG antibody to gB, gHgLgO and pentamer gHgLpUL128L were overlapping in the two patient groups. In conclusion, while a valid HCMV‐specific T‐cell response was detected in more than 90% of LVL patients, >90% of HVL patients lacked an adequate T‐cell response. Antibody responses did not appear to be associated directly or indirectly with protection. This article is protected by copyright. All rights reserved.
Daniele Lilleri; Paola Zelini; Chiara Fornara; Federica Zavaglio; Teresa Rampino; Laurent Perez; Elisa Gabanti; Giuseppe Gerna. Human cytomegalovirus (HCMV)-specific T cell but not neutralizing or IgG binding antibody responses to glycoprotein complexes gB, gHgLgO, and pUL128L correlate with protection against high HCMV viral load reactivation in solid-organ transplant recipients. Journal of Medical Virology 2018, 90, 1620 -1628.
AMA StyleDaniele Lilleri, Paola Zelini, Chiara Fornara, Federica Zavaglio, Teresa Rampino, Laurent Perez, Elisa Gabanti, Giuseppe Gerna. Human cytomegalovirus (HCMV)-specific T cell but not neutralizing or IgG binding antibody responses to glycoprotein complexes gB, gHgLgO, and pUL128L correlate with protection against high HCMV viral load reactivation in solid-organ transplant recipients. Journal of Medical Virology. 2018; 90 (10):1620-1628.
Chicago/Turabian StyleDaniele Lilleri; Paola Zelini; Chiara Fornara; Federica Zavaglio; Teresa Rampino; Laurent Perez; Elisa Gabanti; Giuseppe Gerna. 2018. "Human cytomegalovirus (HCMV)-specific T cell but not neutralizing or IgG binding antibody responses to glycoprotein complexes gB, gHgLgO, and pUL128L correlate with protection against high HCMV viral load reactivation in solid-organ transplant recipients." Journal of Medical Virology 90, no. 10: 1620-1628.
An incorrect definition of immune status to human cytomegalovirus (HCMV) can lead to incorrect management of pregnant women. Aims of the study were: i) to describe 10 cases of unconfirmed HCMV IgG-seroconversion in pregnancy; ii) to develop a panel of confirmatory tests to define HCMV serostatus; iii) to investigate the frequency of false IgG-positive results in pregnant women screened with the LIAISON®CMVIgGII automated assay. Blood samples from 10 pregnant women referred for HCMV IgG-seroconversion were examined to confirm/exclude a primary infection. In addition, samples were tested for HCMV IgG by immunoblotting, neutralization assay, and ELISA against gB, gH/gL/pUL128L and gH/gL/gO recombinant glycoproteins. LIAISON®CMVIgGII results obtained on 1,158 pregnant women were reviewed and samples with low IgG titers were further investigated. A primary infection was excluded in the 10 women referred for HCMV IgG seroconversion. None of them was confirmed to be IgG-seropositive. Of the 1,158 women prenatally screened by LIAISON®CMVIgGII, 678 (59%) were IgG-positive and, of these, 40 (5.9%) showed low levels of IgG (14–50 U/mL). Thirty-three women with low IgG-positivity were further tested by confirmatory tests and 11 (33.3%) were found to be non reactive to HCMV. At least 1.6% (11/678) women who tested positive with LIAISON®CMVIgGII were found to be seronegative when tested with confirmatory tests. These women should be informed to reduce the risk of a primary HCMV infection. Furthermore, should a congenital infection occur in any of these women, a maternal non-primary infection could be erroneously diagnosed.
Milena Furione; Antonella Sarasini; Alessia Arossa; Chiara Fornara; Daniele Lilleri; Laurent Perez; Maurizio Parea; Maurizio Zavattoni; Arsenio Spinillo; Piero Marone; Fausto Baldanti; Fornara Chiara. False human cytomegalovirus IgG-positivity at prenatal screening. Journal of Clinical Virology 2018, 104, 34 -38.
AMA StyleMilena Furione, Antonella Sarasini, Alessia Arossa, Chiara Fornara, Daniele Lilleri, Laurent Perez, Maurizio Parea, Maurizio Zavattoni, Arsenio Spinillo, Piero Marone, Fausto Baldanti, Fornara Chiara. False human cytomegalovirus IgG-positivity at prenatal screening. Journal of Clinical Virology. 2018; 104 ():34-38.
Chicago/Turabian StyleMilena Furione; Antonella Sarasini; Alessia Arossa; Chiara Fornara; Daniele Lilleri; Laurent Perez; Maurizio Parea; Maurizio Zavattoni; Arsenio Spinillo; Piero Marone; Fausto Baldanti; Fornara Chiara. 2018. "False human cytomegalovirus IgG-positivity at prenatal screening." Journal of Clinical Virology 104, no. : 34-38.