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Postnatal human cytomegalovirus (HCMV) infection in newborns is well characterized for preterm infants but less so for term infants. We sought to analyze the rates and routes of HCMV transmission in full-term infants during the first year of life. A cohort of 120 HCMV seropositive mothers and their 122 newborns were tested after delivery for HCMV-DNA shedding in different bodily fluids. Postnatal HCMV infection was defined as the detection of >2.5 × 10 2 HCMV-DNA copies/mL in infants' saliva swabs. Maternal neutralizing antibody serum titer, HCMV-specific T-cell response, and HCMV glycoprotein B immunoglobulin G on breastmilk were analyzed. HCMV shedding was detected in 67 of 120 mothers (55.8%), and 20 of 122 infants (16.4%) developed HCMV infection within the first 3 months of life. Six additional infants were infected during the first year, for a postnatal infection rate of 21.3%. Viral shedding was more frequent in breastmilk than saliva, urine, and vaginal secretions, and the mothers of infected infants showed higher levels of HCMV-DNA in milk. No association was found between the antibody levels in serum or milk and maternal viral shedding, whereas a slightly lower frequency of HCMV-specific CD4 + T-cells with long-term memory phenotype was observed in women with HCM-DNA-positive milk. About one out of five infants develop HCMV infection within the first year of life. Breastmilk appears the major route of transmission of the infection, maternal saliva has a minor role whereas the role of vaginal secretions is negligible., (© 2023 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Human cytomegalovirus (HCMV) infection represents a major complication for solid organ transplant recipients. The aim of this study was to verify if the measurement of HCMV-specific T-cells could help to identify patients protected against HCMV disease cytokine flow cytometry using infected dendritic cells as stimulus (CFC-iDC, which discriminates between CD4 + and CD8 + T cells), and ELISPOT, using infected cell lysate (ELISPOT-iCL) or pp65 (ELISPOT-pp65) as stimulus, were adopted. Among the 47 kidney transplant recipients (KTR) enrolled, 29 had a self-resolving HCMV infection (Controllers) and 18 required antiviral treatment (Non-Controllers). HCMV-specific T-cell frequency at the peak of HCMV infection identified Controllers and Non-Controllers, although the diagnostic performance of CD8 + CFC-iDC (area under the curve [AUC] of the receiver-operator characteristic curve: 0.65) was lower than that of CD4 + CFC-iDC (AUC: 0.83), ELISPOT-iCL (AUC: 0.83) and ELISPOT-pp65 (AUC: 0.80). CFC-iDC detected a protective immune reconstitution significantly earlier (median time: 38 days) than ELISPOT-iCL and ELISPOT-pp65 (median time: 126 and 133 days, respectively). Time to protective immune reconstitution in Non-Controllers was significantly longer than in Controllers with the ELISPOT and the CD4 + CFC-iDC assays, but not with CD8 + CFC-iDC. The majority of patients did not require antiviral treatment after protective immune reconstitution, with the exception of five patients according to CFC-iDC assay, one patient according to ELISPOT-iCL assay and three patients according to ELISPOT-pp65 assay. Monitoring the HCMV-specific immunological reconstitution with is effective in discriminating KTR at risk of or protected from HCMV disease and the ELISPOT assays are suitable for implementation in the clinical setting., (© 2023 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

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 transplant recipients (n = 40) and heart transplant recipients (n = 12). Overall, patients were divided into 2 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 enzyme-linked immunosorbent assay-IgG antibodies to gB, gHgLgO, and pentamer gHgLpUL128L were overlapping in the 2 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., (© 2018 Wiley Periodicals, Inc.)