Background
Respiratory syncytial virus (RSV) is a major cause of severe respiratory disease in young children and the elderly. Protective immunity is not generated after repeated infections, but vaccination may hopefully prove effective.
Methods
This phase 2 clinical study investigated a multivalent RSV vaccine (MVA-BN®-RSV) designed to induce broad antibody and cellular immune responses by encoding RSV surface proteins F, G (for both A and B subtypes), and internal antigens (M2, N). This study evaluated the immune response in adults ≥55 years to identify the optimal MVA-BN-RSV dose and vaccination schedule.
Results
A single dose increased the levels of neutralizing (PRNT to RSV A and B) and total (IgG and IgA ELISA) antibodies (1.6 to 3.4-fold increase from baseline) and induced a broad Th1-biased cellular immune response (IFN-γ ELISPOT) to all 5 vaccine inserts (5.4 to 9.7-fold increases). Antibody responses remained above baseline for 6 months. A 12-month booster dose elicited a booster effect in antibody and T cell responses (up to 2.8-fold from pre-boost levels). No drug-related serious adverse events were reported.
Conclusions
MVA-BN-RSV induces a broad immune response that persists at least 6 months and can be boosted at 12 months, without significant safety findings.
Clinical Trials Registration
NCT02873286
In a previous retrospective study, we demonstrated the prognostic value of protein tyrosine kinase 6 (PTK6) protein expression in breast carcinomas. Here, we analyzed PTK6 gene amplification using fluorescence in situ hybridization technique in a cohort of 426 invasive breast carcinomas and compared it with PTK6 expression level as well as with the clinical outcome of patients. Forty-five percent of tumors show increased PTK6 gene copy numbers when compared to normal tissue. Most of these, however, were related to chromosome 20 polysomy (30%), while gene amplification accounted for only 15%. Only "low level" amplification of the PTK6 gene, with up to eight signals per nucleus, was found. The PTK6 cytogenetic status (normal, gene amplification, polysomy 20) was not associated with histopathological parameters or with the protein expression of HER receptors. No statistical association was identified between PTK6 gene status and expression level. Further, the PTK6 gene status does not influence the disease-free survival of patients at > or = 240 months. Based on these results, we state that the PTK6 overexpression is not essentially attributed to gene amplification, and the PTK6 protein expression-but not gene status-is of prognostic value in breast carcinomas. PTK6 protein overexpression may result from polysomy 20 in a minority of the tumors. In a marked proportion of tumors, however, the overexpression is likely to be caused by posttranscriptional regulation mechanisms.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.