In search of the optimal platform for Post-Allogeneic SCT immunotherapy in relapsed multiple myeloma: a systematic review.

Allogeneic stem cell transplantation (allo-SCT) has the potential to induce sustained remissions in patients with multiple myeloma (MM). Currently, allo-SCT is primarily performed in high-risk MM patients, most often in the setting of early relapse after first-line therapy with autologous SCT. However, the implementation of allo-SCT for MM is jeopardized by high treatment-related mortality (TRM) rates as well as high relapse rates. In this systematic review, we aimed to identify a safe allo-SCT strategy that has optimal 1-year results regarding mortality, relapse and severe GvHD, creating opportunities for post-transplantation strategies to maintain remissions in the high-risk group of relapsed MM patients. Eleven studies were included. Median PFS ranged from 5.2 to 36.8 months and OS was 13.0 to 63.0 months. The relapse related mortality at 1 year varied between 0 and 50% and TRM between 8 and 40%. Lowest GvHD incidences were reported for conditioning regimens with T-cell depletion using ATG or graft CD34+ selection. Similar strategies could lay the foundation for a post-transplant immune platform, this should be further evaluated in prospective clinical trials.

Efficacy of inactivated infectious bursal disease (IBD) vaccines: comparison of serology with protection of progeny chickens against IBD virus strains of varying virulence.

The efficacy of inactivated infectious bursal disease vaccines was determined by measuring both the antibody response of vaccinated chickens and clinical protection of progeny chicks from vaccinated dams. Similar virus neutralizing (VN) antibody titres were obtained in 4-week-old chickens and mature hens after vaccination with one vaccine dose. VN titres below 10 log 2 increased considerably between the fourth and seventh week after vaccination in 4-week-old chickens as well as in mature chickens. All 2-week-old progeny chicks with serum VN antibody titres of at least 9 log 2 were clinically protected against the classical virulent 52/70 infectious bursal disease virus (IBDV) strain, as well as against the very virulent IBDV (vvIBDV) strain D6948. However, vaccination often did not prevent subclinical infection in these 2-week-old progeny chicks, which often resulted in severe lymphocyte depletion in the bursa of Fabricius. Even a serum VN titre of 11 log 2 was not always sufficient to prevent severe bursal damage. Although 52/70 IBDV and vvIBDV were equally pathogenic in 2-weekold specific pathogen free chickens, significant higher maternal antibody titres were required to prevent the adverse effects of vvIBDV in comparison with 52/70 IBDV. The relation between the serological response of chickens after application of inactivated IBD vaccines and the protection of progeny chicks of vaccinated dams depended on both the virulence of the IBDV challenge strain and the IBDV strain in the vaccine.

Antigen quantification as in vitro alternative for potency testing of inactivated viral poultry vaccines.

Routine batch control of licensed inactivated viral vaccines for poultry usually includes a potency assay as a measure of vaccine efficacy. Potency assays often consist of vaccination-challenge experiments in the target species or in laboratory animals. Instead of measuring the protection of vaccinated animals against virulent pathogens, the serological response after vaccination can be quantified for some vaccines. In vitro antigen quantification assays would be attractive alternatives for the current potency assays because the time and costs involved could be greatly reduced and animal use could be avoided. Such in vitro assays will only be acceptable when the correlation between results and efficacy or potency has been demonstrated convincingly. The results of our studies on antigen quantification assays indicate that, in principle, quantification of viral antigens from inactivated oil-adjuvanted vaccines is feasible and reproducible using specially developed antigen capture ELISAs in combination with specific software for statistical analysis of the ELISA data. We have developed methods to quantify the haemagglutination-neuraminidase (HN) and fusion (F) proteins of Newcastle disease virus (NDV), the viral protein 3 (VP3) of the infectious bursal disease virus (IBDV), and the spike-1 (S1) protein of the infectious bronchitis virus (IBV). Vaccination experiments with inactivated ND vaccines indicate that the in vitro quantified HN- or F-proteins of NDV are reliable indicators of the serological response after vaccination.