Search

Background/Objectives: Human cytomegalovirus (HCMV) is the most frequent cause of congenital infections. The HCMV-specific T-cell response in primary infection may help define reliable correlates of immune protection in pregnancy. In this study, the antigen-specific T-cell response against different HCMV proteins (IE-1, pp65, gB, gHgLpUL128L) was investigated in pregnant women with primary infection and in control subjects with remote infection to identify possible components of a vaccine. Methods: Blood samples from 35 pregnant women with HCMV primary infection and 30 HCMV-seropositive healthy adult subjects with remote infection were tested. The antigen-specific T-cell response was measured using cytokine intracellular staining after stimulation with IE-1, pp65, gB and gHgLpUL128L peptides pool. Results: The pp65-specific CD4+ T-cell response was higher in pregnant women with HCMV primary infection at the late time point and in control subjects with remote infection, while the pregnant women at the early time point showed a higher gB-specific CD8+ T-cell response. Regarding the CD4+ and CD8+ T-cell phenotypes, we observed that HCMV-specific CD4+ and CD8+ T cells expressing CD45RA+ remained constant in pregnant women with primary infection at the early and late time points and in subjects with remote infection, while HCMV-specific CD4+ and CD8+ T cells expressing IL-7R+ or producing IL-2 were higher in control subjects with remote infection than in pregnant women with HCMV primary infection. Conclusions: The T-cell response was higher against gB in the early phase of infection and against pp65 in the late phase. Therefore, these proteins should be taken into consideration as candidates for a vaccine. [ABSTRACT FROM AUTHOR]

Human cytomegalovirus (HCMV) infection remains a major complication for solid organ transplant recipients (SOTRs). The aim of this study was to evaluate the role of HCMV-specific T cell immunity measured at the time of the HCMV-DNA peak in predicting the spontaneous clearance of infection. The performance of cytokine flow cytometry using infected dendritic cells (CFC-iDC), infected cell lysate (CFC-iCL) and pp65 peptide pool (CFC-pp65 pool) as stimuli, as well as ELISPOT assays using infected cell lysate (ELISPOT-iCL) and the pp65 peptide pool (ELISPOT-pp65 pool), was analysed. Among the 40 SOTRs enrolled, 16 patients (40%) required antiviral treatment for an HCMV infection (Non-Controllers), while the others spontaneously cleared the infection (Controllers). At the HCMV-DNA peak, the number of HCMV-specific CD4+ T cells detected by the CFC-iDC, CFC-iCL and CFC-pp65 pool assays in Controllers was higher than that detected in Non-Controllers, while no difference was observed in terms of HCMV-specific CD8+ T cell response. The same trend was observed when the HCMV-specific T cell response was measured by ELISPOT-iCL and ELISPOT-pp65 pool. We observed that the CD4+ CFC-pp65 pool assay was the best predictor of self-resolving HCMV infection at the time of the HCVM-DNA peak. The CFC-pp65 pool assay is able to discriminate between CD4+ and CD8+ T cell responses and could be used in daily clinical practice. [ABSTRACT FROM AUTHOR]

In the setting of infectious diseases, antibodies show different functions beyond neutralizing activity. In this study, we investigated the activation of NK cells in vitro in the presence of human cytomegalovirus (HCMV)-specific antibodies and their potential role in the control of HCMV infection through antibody-dependent cell cytotoxicity (ADCC). Retinal pigmented epithelial cells (ARPE-19) infected with the HCMV strain VR1814 were co-cultured with cytokine-activated peripheral blood mononuclear cells (PBMCs) in the presence of sera collected from 23 HCMV-seropositive and 9 HCMV-seronegative donors. Moreover, 13 pregnant women sampled 3 and 6 months after HCMV primary infection and 13 pregnant women with pre-conception immunity were tested and compared. We determined the percentage of activated NK cells via the analysis of CD107a expression as a marker of degranulation. Significantly higher levels of NK-cell activation were observed using 1/100 and 1/10 dilutions of sera from HCMV-seropositive individuals, and when cells were infected for 96 and 120 h, suggesting that NK cells are activated by antibodies directed against late antigens. In the absence of serum NK cells, activation was negligible. In seropositive subjects, the median percentages of CD107a-positive NK cells in the presence of autologous serum and pooled HCMV-positive serum were similar (14.03% [range 0.00–33.56] and 12.42% [range 1.01–46.00], respectively), while NK-cell activation was negligible using an HCMV-negative serum pool. In HCMV-seronegative subjects, the median percentage of activated NK cells was 0.90% [range 0.00–3.92] with autologous serum and 2.07% [0.00–5.76] in the presence of the HCMV-negative serum pool, while it was 8.97% [0.00–26.49] with the pool of HCMV-positive sera. NK-cell activation using hyperimmune globulin is comparable to what is obtained using autologous serum. Sera from subjects at 3 and 6 months post primary infection showed a lower capacity of NK-cell activation than sera from subjects with past infection (p < 0.001). NK activation against HCMV-infected epithelial cells is dependent on the presence of HCMV-specific antibodies. This serum activity increases with time after the onset of HCMV infection. The protective role of NK-cell activation by HCMV-specific serum antibodies should be verified in clinical settings. [ABSTRACT FROM AUTHOR]

We compared the development and persistence of antibody and T-cell responses elicited by the mRNA BNT162b2 vaccine or SARS-CoV-2 infection. We analysed 37 post-COVID-19 patients (15 with pneumonia and 22 with mild symptoms) and 20 vaccinated subjects. Anti-Spike IgG and neutralising antibodies were higher in vaccinated subjects and in patients with pneumonia than in patients with mild COVID-19, and persisted at higher levels in patients with pneumonia while declining in vaccinated subjects. However, the booster dose restored the initial antibody levels. The proliferative CD4+ T-cell response was similar in vaccinated subjects and patients with pneumonia, but was lower in mild COVID-19 patients and persisted in both vaccinated subjects and post-COVID patients. Instead, the proliferative CD8+ T-cell response was lower in vaccinated subjects than in patients with pneumonia, decreased six months after vaccination, and was not restored after the booster dose. The cytokine profile was mainly TH1 in both vaccinated subjects and post-COVID-19 patients. The mRNA BNT162b2 vaccine elicited higher levels of antibody and CD4+ T-cell responses than those observed in mild COVID-19 patients. While the antibody response declined after six months and required a booster dose to be restored at the initial levels, the proliferative CD4+ T-cell response persisted over time. [ABSTRACT FROM AUTHOR]

Slow cytomegalovirus-specific CD4+ and CD8+ T-cell differentiation: 10-year follow-up of primary infection in a small number of immunocompetent hosts. Human cytomegalovirus, memory inflation, memory T cells, primary infection, T cells. [Extracted from the article]

• Circulation of heterogeneous variants during the pandemic waves. • One hundred and forty-seven mutations emerged in 2 years. • Vaccination and competition among variants caused the rise and fall of the circulating variants. Since the beginning of the pandemic, SARS-CoV-2 has shown genetic variability. All the variants that have sustained pandemic waves have shown several mutations, especially in the Spike protein that could affect viral pathogenesis. A total of 15,729 respiratory samples, collected between December 2020 and August 2022, have been included in this study. We report the circulation of SARS-CoV-2 variants in the Lombardy region, Italy, in a 2-year study period. Alpha, Delta, and Omicron variants became predominant causing the majority of cases whereas Beta or Gamma variants mostly caused local outbreaks. Next-generation sequencing revealed several mutations and few deletions in all of the main variants. For example, 147 mutations were observed in the Spike protein of Omicron sublineages; 20% of these mutations occurred in the receptor-binding domain region. [ABSTRACT FROM AUTHOR]

Background: Pregnant women may be at an increased risk of developing severe or critical disease associated with the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection causing severities during pregnancy. We performed a prospective study to describe the impact of SARS-CoV-2 infection on pregnancy outcomes and on the newborn, depending on the severity of the disease. The antibody response and persistence of SARS-CoV-2 anti-Spike (S) IgG, IgA and anti-Nu- cleocapsid (NCP) IgG, was investigated., Methods: A total of 48 pregnant women with SARS-CoV-2 infection were enrolled, and sequential serum samples from 30 of them were collected until one year after infection. Outcomes of pregnan- cy and newborn parameters were evaluated in comparison with 200 uninfected controls., Results: Asymptomatic infection was observed in 31/48 women (64.5%), mild COVID-19 in 12/48 women (25.0%), while 5/48 women (10.5%) developed pneumonia. Women with pneumonia mount- ed significantly higher levels of anti-S IgG, IgA and anti-NCP IgG between 1 and 3 months after onset of infection compared to asymptomatic women. Anti-S IgG persisted in the majority of women from 6 months to at least one year after infection, especially in those with symptomatic infection and pneumonia, while anti-S IgA and anti-NCP IgG declined earlier. Pregnancy complications and new- born parameters were not significantly different from those observed in uninfected controls., Conclusion: Anti-SARS-CoV-2 antibody development and persistence was not impaired in pregnant women, while SARS-CoV-2 infection did not cause major pregnancy or newborn complications in asymptomatic or symptomatic women, nor in women with pneumonia receiving prompt clinical care.