Human cytomegalovirus (HCMV) is an important pathogen in transplant patients and in congenital infection. Previously, we demonstrated that vaccination with a recombinant viral glycoprotein B (gB)/MF59 adjuvant formulation before solid organ transplant reduced viral load parameters post transplant. Reduced posttransplant viremia was directly correlated with antibody titers against gB consistent with a humoral response against gB being important. Here we show that sera from the vaccinated seronegative patients displayed little evidence of a neutralizing antibody response against cell-free HCMV in vitro. Additionally, sera from seronegative vaccine recipients had minimal effect on the replication of a strain of HCMV engineered to be cell-associated in a viral spread assay. Furthermore, although natural infection can induce antibody-dependent cellular cytotoxicity (ADCC) responses, serological analysis of seronegative vaccinees again presented no evidence of a substantial ADCC-promoting antibody response being generated de novo. Finally, analyses for responses against major antigenic domains of gB following vaccination were variable, and their pattern was distinct compared with natural infection. Taken together, these data argue that the protective effect elicited by the gB vaccine is via a mechanism of action in seronegative vaccinees that cannot be explained by neutralization or the induction of ADCC. More generally, these data, which are derived from a human challenge model that demonstrated that the gB vaccine is protective, highlight the need for more sophisticated analyses of new HCMV vaccines over and above the quantification of an ability to induce potent neutralizing antibody responses in vitro.

Purpose To examine the feasibility, acceptability, and efficacy of online supportive care interventions targeting prostate cancer survivors (PCS). Methods Studies were identified through structured searches of PubMed, Embase and PsycINFO databases, and bibliographic review. Inclusion criteria were (1) examined feasibility, acceptability, or efficacy of an online intervention designed to improve supportive care outcomes for PCS; (2) presented outcome data collected from PCS separately (if mixed cancer); and (3) evaluated efficacy outcomes using randomized controlled trial (RCT) design. Results Sixteen studies met inclusion criteria; ten were classified as RCTs. Overall, 2446 men (average age 64 years) were included. Studies reported on the following outcomes: feasibility and acceptability of an online intervention (e.g., patient support, online medical record/follow-ups, or decision aids); reducing decisional conflict/distress; improving cancer-related distress and health-related quality of life; and satisfaction with cancer care. Conclusion We found good preliminary evidence for online supportive care among PCS, but little high level evidence. Generally, the samples were small and unrepresentative. Further, inadequate acceptability measures made it difficult to determine actual PCS acceptability and satisfaction, and lack of control groups precluded strong conclusions regarding efficacy. Translation also appears minimal; few interventions are still publicly available. Larger trials with appropriate control groups and greater emphasis on translation of effective interventions is recommended. Implications for Cancer Survivors Prostate cancer survivors have a variety of unmet supportive care needs. Using online delivery to improve the reach of high-quality supportive care programs could have a positive impact on health-related quality of life among PCS.

Human cytomegalovirus (HCMV) latency and reactivation rely on a complex interplay between cellular differentiation, cell signaling pathways, and viral gene functions. HCMV reactivation in dendritic cells (DCs) is triggered by IL-6 and extracellular signal-regulated kinase (ERK)–mitogen-activated protein kinase signaling. However, activation of the same pathway fails to reactivate HCMV in other myeloid cell types, despite this signaling axis being active in those cells. We hypothesized that IL-6–induced ERK activation initiates the changes in chromatin structure required for viral reactivation but that a concomitant signal is necessary to complete the changes in chromatin structure required for gene expression to occur. Using a differential phosphoproteomics approach in cells that do or do not support IL-6–induced viral reactivation, we identified the concomitant activation of an Src family kinase (SFK), hematopoietic cell kinase (HCK), specifically in DCs in response to IL-6. Pharmacological and genetic inhibition of HCK activity indicated that HCK is required for HCMV reactivation. Furthermore, the HCK/SFK activity was linked to recruitment of the monocytic leukemia zinc finger protein (MOZ) histone acetyltransferase to the viral promoter, which promoted histone acetylation after ERK-mediated histone phosphorylation. Importantly, pharmacological and genetic inhibition of MOZ activity prevented reactivation. These results provide an explanation for the selective activation of viral gene expression in DCs by IL-6, dependent on concomitant SFK and ERK signaling. They also reveal a previously unreported role for SFK activity in the regulation of chromatin structure at promoters in eukaryotic cells via MOZ histone acetyltransferase activity.