OBJECTIVES:Immunogenicity and safety of recombinant zoster vaccine (RZV) were evaluated in the long-term and after revaccination in kidney transplant (KT) recipients on daily chronic immunosuppressive treatment. METHODS:This phase 3b, single-arm, multicenter trial, evaluated KT recipients for varicella zoster virus (VZV) glycoprotein E (gE)-specific humoral and cell-mediated immune (CMI) responses and safety ∼4-8 years post-primary RZV series (two doses) given at ≥18 years of age; and after revaccination (two doses, one month apart), ∼6-8 years post-primary RZV series. Solicited and unsolicited adverse events (AEs) were recorded for seven and 30 days after each revaccination dose. Serious AEs (SAEs), including biopsy-proven allograft rejection and potential immune-mediated diseases, were recorded throughout the study. RESULTS:68 participants were enrolled and 47 revaccinated. Persistent humoral and CMI responses remained ≥2.4-fold and ≥6.1-fold above pre-vaccination levels. One revaccination dose provided robust humoral (22.3-fold) and CMI (276.2-fold) above pre-vaccination responses. No vaccine-related SAEs were observed. CONCLUSIONS:This study demonstrates sustained immunogenicity against VZV gE for up to ≥8 years, functional immune memory with a robust anamnestic response at 6-8 years, and an acceptable safety profile after revaccination, reinforcing RZV's value for herpes zoster prevention in adult KT recipients on daily immunosuppression. CLINICAL TRIAL REGISTRATION:NCT04176939.

Compared with the general population, older adults with immune senescence and individuals who are immunocompromised (IC) due to disease or immunosuppressive therapy are at increased risk for herpes zoster (HZ) and its associated complications, which can be debilitating and life-threatening. Vaccination can be an effective strategy against HZ and studies have shown that HZ vaccination in IC individuals can elicit immune responses and provide protection from infection. Recently, the first approvals have been granted in the United States and the European Union for the recombinant HZ vaccine (RZV) in adults >= 18 years of age at risk of HZ due to immunodeficiency or immunosuppression. Existing systematic reviews have highlighted the risks for HZ in limited immunocompromising conditions and have only examined clinical data for RZV. This review details the risks and burden of HZ in a broad range of clinically relevant IC populations and summarizes key efficacy and safety data for RZV and live HZ vaccine in these individuals. Research has shown IC individuals can benefit from HZ vaccination; however, these insights have yet to be fully incorporated into vaccination guidelines and clinical care. Clinicians should consider HZ vaccination in eligible at-risk populations to protect against HZ and its associated complications and thereby, reduce the burden that HZ poses on the healthcare system. Electronic health records and linked personal health records could be used to identify and contact patients eligible for HZ vaccination and provide clinical decision support-generated alerts for missing or delayed vaccinations. This review will help clinicians identify eligible IC individuals who may benefit from HZ vaccination. A video abstract linked to this article is available on Figshare https://doi.org/10.6084/m9.figshare. 21517605. (c) 2022 GlaxoSmithKline Biologicals S.A. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

ABSTRACT Immunocompromised (IC) persons are at increased risk for herpes zoster (HZ) and its complications, mainly due to impairment of cell-mediated immunity (CMI). The adjuvanted recombinant zoster vaccine (RZV) demonstrated efficacy against HZ in autologous hematopoietic stem cell transplant (auto-HSCT) recipients and hematologic malignancy (HM) patients. We review immune responses to RZV in 5 adult IC populations, 4 of which were receiving multiple, concomitant immunosuppressive medications: auto-HSCT and renal transplant recipients, HM and solid tumor patients, and human immunodeficiency virus-infected adults. Although administered in most cases when immunosuppression was near its maximum, including concomitantly with chemotherapy cycles, RZV induced robust and persistent humoral and, more importantly, CMI responses in all 5 IC populations. Based on the overall clinical data generated in older adults and IC individuals, RZV is expected to provide benefit in a broad adult population at risk for HZ.

Immunocompromised (IC) persons are at increased risk for herpes zoster (HZ) and its complications, mainly due to impairment of cell-mediated immunity (CMI). The adjuvanted recombinant zoster vaccine (RZV) demonstrated efficacy against HZ in autologous hematopoietic stem cell transplant (auto-HSCT) recipients and hematologic malignancy (HM) patients. We review immune responses to RZV in 5 adult IC populations, 4 of which were receiving multiple, concomitant immunosuppressive medications: auto-HSCT and renal transplant recipients, HM and solid tumor patients, and human immunodeficiency virus-infected adults. Although administered in most cases when immunosuppression was near its maximum, including concomitantly with chemotherapy cycles, RZV induced robust and persistent humoral and, more importantly, CMI responses in all 5 IC populations. Based on the overall clinical data generated in older adults and IC individuals, RZV is expected to provide benefit in a broad adult population at risk for HZ.

Abstract Background The incidence of herpes zoster is up to 9 times higher in immunosuppressed solid organ transplant recipients than in the general population. We investigated the immunogenicity and safety of an adjuvanted recombinant zoster vaccine (RZV) in renal transplant (RT) recipients ≥18 years of age receiving daily immunosuppressive therapy. Methods In this phase 3, randomized (1:1), observer-blind, multicenter trial, RT recipients were enrolled and received 2 doses of RZV or placebo 1–2 months (M) apart 4–18M posttransplant. Anti–glycoprotein E (gE) antibody concentrations, gE-specific CD4 T-cell frequencies, and vaccine response rates were assessed at 1M post–dose 1, and 1M and 12M post–dose 2. Solicited and unsolicited adverse events (AEs) were recorded for 7 and 30 days after each dose, respectively. Solicited general symptoms and unsolicited AEs were also collected 7 days before first vaccination. Serious AEs (including biopsy-proven allograft rejections) and potential immune-mediated diseases (pIMDs) were recorded up to 12M post–dose 2. Results Two hundred sixty-four participants (RZV: 132; placebo: 132) were enrolled between March 2014 and April 2017. gE-specific humoral and cell-mediated immune responses were higher in RZV than placebo recipients across postvaccination time points and persisted above prevaccination baseline 12M post–dose 2. Local AEs were reported more frequently by RZV than placebo recipients. Overall occurrences of renal function changes, rejections, unsolicited AEs, serious AEs, and pIMDs were similar between groups. Conclusions RZV was immunogenic in chronically immunosuppressed RT recipients. Immunogenicity persisted through 12M postvaccination. No safety concerns arose. Clinical Trials Registration NCT02058589.

Abstract Background Immunocompromised (IC) populations are at increased risk of developing herpes zoster (HZ) due to disease- and/or therapy-induced immunosuppression. The adjuvanted recombinant zoster vaccine (RZV) has demonstrated 68.2% efficacy in preventing HZ in autologous hematopoietic stem cell transplant (HSCT) recipients and 87.2% efficacy in a post-hoc analysis in hematologic malignancy (HM) patients ≥ 18 years of age (YOA). Here we present the immunogenicity of RZV in representative IC populations. Methods Our analysis includes five phase I/II/III clinical trials conducted worldwide between 2010–2017 (Table 1) in IC populations (autologous HSCT, human immunodeficiency virus [HIV]-infected, HM, solid tumor [ST] on chemotherapy and renal transplant [RT] patients) ≥ 18 YOA. Anti-glycoprotein E (gE) antibody geometric mean concentrations (GMCs) and gE-specific CD4 T cell frequencies were descriptively evaluated by age group (18–49 YOA and ≥ 50 YOA) and overall at 1 month (M) and 12M post-last RZV dose. Table 1. Clinical studies with immunocompromised populations included in our analysis Results The according-to-protocol cohorts for immunogenicity from the included trials are presented in Table 1. At 1M post-last RZV dose, anti-gE GMCs and median CD4 T-cell frequencies increased in all IC populations compared to pre-vaccination and persisted above baseline up to 12M post-last RZV dose (Figures 1 and 2). No meaningful differences were seen between age groups in terms of humoral (except a slight trend for stronger responses in the 18–49 YOA RT and HM patients compared to their corresponding ≥ 50 YOA group) and gE-specific CD4 T-cell responses in any of the IC populations. Figure 1. Humoral immune responses to RZV in immunocompromised populations (adapted ATP cohort for humoral immunogenicity) Figure 2. Cell-mediated immune responses to RZV in immunocompromised populations (adapted ATP cohort for cell-mediated immunogenicity) Conclusion RZV induced robust and persistent humoral and cell-mediated immune (CMI) responses that lasted up to at least 12M post-last vaccination in all evaluated IC populations. Humoral responses in the IC populations were robust although not as strong as in the non-IC adults ≥ 50 YOA. CMI responses were mostly similar across IC populations and adults ≥ 50 YOA, with a potent response occurring even in ST patients undergoing chemotherapy. This data shows that RZV is immunogenic even in severely IC adults. Funding: GlaxoSmithKline Biologicals SA Acknowledgment: M Maior/S Hulsmans (Modis c/o GSK) provided writing/editorial support Disclosures Alemnew F. Dagnew, MD, MSc, GSK group of companies (Employee, Shareholder) Peter Vink, MD, GSK group of companies (Employee, Shareholder) Mamadou Drame, MSc, GSK group of companies (Employee) David Willer, PhD, GSK group of companies (Employee, Shareholder) Bruno Salaun, PhD, GSK group of companies (Employee) Anne Schuind, MD, GSK (Employee, Other Financial or Material Support, own GSK stock options or restricted shares as part of renumeration)

Background The adjuvanted recombinant zoster vaccine (RZV) has demonstrated >90% efficacy against herpes zoster in adults >= 50 years of age and 68% efficacy in autologous hematopoietic stem cell transplant recipients >= 18 years of age. We report the immunogenicity and safety of RZV administered to patients with solid tumors (STs) before or at the start of a chemotherapy cycle. Method In this phase 2/3 observer-blind, multicenter study (NCT01798056), patients with STs who were >= 18 years of age were randomized (1:1) to receive 2 doses of RZV or placebo 1-2 months apart and stratified (4:1) according to the timing of the first dose with respect to the start of a chemotherapy cycle (first vaccination 8-30 days before the start or at the start [+/- 1 day] of a chemotherapy cycle). Anti-glycoprotein E (gE) antibody concentrations, gE-specific CD4(+) T cell frequencies, and vaccine response rates (VRRs) were assessed 1 month after dose 1 and 1 and 12 months after dose 2. Reactogenicity and safety were assessed in the total vaccinated cohort through 12 months after dose 2. Results There were 232 participants in the total vaccinated cohort, 185 participants in the according-to-protocol cohort for humoral immunogenicity, and 58 participants in the according-to-protocol cohort for cell-mediated immunogenicity. Postvaccination anti-gE antibody concentrations, gE-specific CD4(+) T cell frequencies and VRRs were higher in RZV recipients than in placebo recipients. Solicited adverse events (AEs) were more frequent among RZV recipients than placebo recipients. Incidence of unsolicited AEs, serious AEs, fatalities, and potential immune-mediated diseases were similar between RZV and placebo recipients. Conclusion RZV was immunogenic in patients with STs receiving immunosuppressive chemotherapies. Humoral and cell-mediated immune responses persisted 1 year after vaccination. No safety concerns were identified.

The efficacy of the non-live adjuvanted recombinant zoster vaccine (RZV, containing a truncated form of varicella-zoster glycoprotein E [gE] and Adjuvant System AS01B) is >90% in adults ≥50 years of age (YOA) (ZOE-50/70) and >68% in hematopoietic stem cell transplant recipients ≥18 YOA (ZOE-HSCT).1 This study (NCT02058589) evaluated immunogenicity and safety of RZV in renal transplant recipients ≥18 YOA receiving immunosuppressive therapy. Previously unreported reactogenicity and 12-month post-last dose safety and immune persistence data are presented. In this phase III, 1:1 randomized, observer-blind, multicenter trial, patients received 2 doses of RZV or placebo. gE-specific immune responses were assessed at 1 (M2) and 12 (M13) months post-dose 2: humoral immunity by vaccine response rate (VRR) and geometric mean antibody concentration (GMC), and cell-mediated immunity (CMI) by VRR and CD4+ T-cell frequency. Solicited general and unsolicited adverse events (AEs) were collected 7 days pre-dose 1 as a within-participant control. Solicited and unsolicited AEs were also recorded for 7 and 30 days after each dose, respectively. Serious AEs (SAE) and potential immune-mediated diseases (pIMDs) were recorded up to study end (M13). Humoral and CMI in the RZV group persisted through M13 appearing higher in the RZV group vs. placebo (Table 1). The frequency of solicited local AEs and of general AEs myalgia and fever was higher in the RZV group vs. placebo and balanced between study groups for the other general AEs, pIMDs and SAEs (including allograft rejections) (Table 2, Figure 1). No concerns regarding renal function were reported. Suspected HZ cases were recorded among 2 RZV and 6 placebo recipients. In the RZV group, within-participant pre- and post-vaccination solicited general AEs were reported at similar rates for fatigue, gastrointestinal symptoms and headache, and higher rates post-vaccination for myalgia, shivering, and fever (Figure 1). RZV was highly immunogenic, eliciting robust humoral and CMI that persisted up to 12 months in adult renal transplant recipients. No safety concerns were identified over a 1-year follow-up. Reference 1. de la Serna, BMT Tandem Meeting 2018, abs LBA2. Funding: GlaxoSmithKline Biologicals SA P. Vink, GSK group of companies: Employee and Shareholder, Salary and stock shares. S. J. Kim, GSK group of companies: Investigator, Research grant and Research support. M. Campins Marti, GSK group of companies: Consultant, Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Research grant and Speaker honorarium. D. Kumar, GSK group of companies: Scientific Advisor, Consulting fee. K. Doucette, GSK group of companies: Investigator, Research support. S. A. McNeil, GSK group of companies: Grant Investigator, Research grant and Research support. L. Campora, GSK group of companies: Employee and Shareholder, Salary. E. Di Paolo, GSK group of companies: Employee, Salary. M. El Idrissi, GSK group of companies: Employee, Salary. M. López-Fauqued, GSK group of companies: Employee, Salary. B. Salaun, GSK group of companies: Employee and Shareholder, Salary. T. Heineman, GSK group of companies: Consultant, Employee and Shareholder, Consulting fee and Salary. L. Oostvogels, GSK group of companies: Employee, Salary and stock and stock option.

Abstract Background The incidence rate of herpes zoster (HZ) in individuals with solid organ transplants (SOTs) is estimated as 8–9 times higher than the rate in the overall US population (3.2/1000 person-years). No vaccine is currently available to prevent HZ in immunocompromised individuals. GSK’s HZ/su candidate vaccine, containing varicella-zoster virus glycoprotein E (gE) and AS01B Adjuvant System, has shown >90% efficacy for HZ prevention in immunocompetent adults ≥50 years of age (YOA). We performed a study to determine immunogenicity and safety of HZ/su in adult renal transplant (RT) recipients (RTR) on chronic immunosuppressive therapy; RT was chosen as it can be representative of SOTs due to the nature of administered immunosuppressive therapies. Methods In this phase III, observer-blind, multicenter study (NCT02058589), RTRs ≥18 YOA were randomized 1:1 to receive 2 doses of HZ/su or placebo intramuscularly 1–2 months apart. gE-specific vaccine response rates (VRRs) and geometric means (GMs) were assessed for humoral and CD4+ cell-mediated immune (CMI) responses 1 month post dose 2 (M2). Solicited adverse events (AEs) were recorded for 7 days and unsolicited AEs and medically-attended AEs (MAEs) for 30 days after each dose. Solicited general and unsolicited AEs were also collected for 7 days prior to dose 1. Potential immune-mediated diseases (pIMDs) and serious AEs (SAEs) were recorded until 1 year post dose 2. Data from dose 1 through M2 is presented. Results At M2, 240 subjects (121 HZ/su; 119 placebo) were included in the humoral immunogenicity according-to-protocol (ATP) cohort. All immunogenicity success criteria were met at M2 (Table 1). VRRs for ATP humoral immune cohort and CMI sub-cohort (72 subjects: 36 HZ/su; 36 placebo) were higher in HZ/su groups. Humoral GM concentrations and CMI GM frequencies were significantly higher in HZ/su compared with placebo groups. The frequency of AEs was higher in HZ/su vs. placebo groups for solicited local AEs, but similar for solicited general AEs, unsolicited AEs, MAEs and SAEs. No pIMDs, vaccine-related SAEs or transplant rejections were reported (Table 2). Conclusion HZ/su was highly immunogenic in adults with RT at M2. No safety concerns were identified. Funding GlaxoSmithKline Biologicals SA Disclosures P. Vink, GSK group of companies: Employee, Salary and stock options and stock granted

Abstract Background No herpes zoster (HZ) vaccine for immunosuppressed individuals is currently available. GSK’s candidate HZ vaccine containing recombinant varicella zoster virus glycoprotein E (gE) subunit and AS01B Adjuvant System (HZ/su) showed >90% efficacy for HZ prevention in immunocompetent adults aged ≥50 years. The HZ incidence in individuals with solid tumors (ST) receiving immunosuppressive chemotherapy (chemo) is estimated as 3–4 times higher than in the overall US population (3.2/1000 person-years). We present HZ/su immunogenicity and safety in ST adults aged ≥18 years. Methods In this phase II/III, observer-blind, multicenter study (NCT01798056), ST adults received 2 doses of HZ/su or placebo intramuscularly 1–2 months apart and were randomized 4:4:1:1 to receive a first dose 8–30 days (D) pre-chemo (HZ/su – HZ/su-PreC group, placebo – Pl-PreC) or on chemo start (±1 D) (HZ/su-OnC, Pl-OnC). Vaccine response rates (VRRs) and geometric means (GMs)/means were evaluated for gE humoral immune and gE-specific CD4+ cell-mediated immune (CMI) responses 1 month (M2) and 12 months (M13) post-dose 2. Solicited adverse events (AEs) were recorded for 7 D and unsolicited and medically-attended AEs (MAEs) for 30 D post each dose. Potential immune-mediated diseases (pIMDs) and serious AEs (SAEs) were recorded until study end. Results 185 subjects (65 HZ/su-PreC, 78 Pl-PreC, 22 HZ/su-OnC, 20 Pl-OnC) were included in the according-to-protocol (ATP) cohort for humoral immunogenicity and 58 (27 HZ/su-PreC, 31 Pl-PreC) in the ATP sub-cohort for CMI. The most common ST were breast tumors (54% HZ/su, 49% placebo), followed by colorectal, lung, then other. Humoral and CMI VRRs were higher in HZ/su than Pl groups at M2 and M13. GM concentration (GMC) was highest at M2 in HZ/su-PreC. M13 GMCs were similar in the HZ/su-PreC and HZ/su-OnC groups (Table 1). The frequency of local solicited AEs was higher in HZ/su than Pl groups (Table 2); that of general solicited, unsolicited AEs, MAEs and SAEs was similar among groups (Table 3). 1 pIMD (Pl-OnC) and 23 fatal SAEs were reported. No SAE was considered vaccine-related by investigators. Conclusion HZ/su was highly immunogenic in ST adults receiving chemo. No safety concerns were raised. Funding GlaxoSmithKline Biologicals SA Disclosures P. Vink, GSK group of companies: Employee, Salary and stock options and stock granted

The impact of alternate routes of vaccine administration, subcutaneous (SC) or intramuscular (IM), on the safety and immunogenicity of herpes zoster subunit candidate vaccine (HZ/su) was assessed in Japanese adults aged ≥ 50 y. During this phase III open-label study, 60 subjects were randomized (1:1) to receive HZ/su through SC or IM routes in a 0, 2 month schedule. Vaccine response rates (VRRs) and geometric mean concentrations (GMCs) of varicella zoster virus glycoprotein E (gE)-specific antibodies were determined by ELISA. Solicited and unsolicited symptoms were recorded for 7 and 30 d after each vaccination and graded 1–3 in severity. Serious adverse events (SAEs) were recorded throughout the study. At one month post-dose 2, VRRs were 100% (95% Confidence Interval (CI): 88.1–100) in both groups; anti-gE antibody GMCs were 44126.1 mIU/ml (95% CI: 36326.1–53601.0) and 45521.5 mIU/ml (95% CI; 37549.5–55185.9) in the SC and IM groups, respectively. Injection site reactions (pain, swelling and redness) were common, and observed more frequently following SC administration. Grade 3 redness and swelling were more frequently observed after SC administration. Fatigue and headache were the most frequently reported general symptoms for both routes of administration. Ten and 7 unsolicited AEs were reported in the SC and IM group, respectively. Two unsolicited AEs (1 in SC; 1 in IM) were considered related to vaccination by the investigator. Three non-fatal SAEs considered unrelated to vaccination were reported during the study. Administration of the HZ/su vaccine candidate resulted in a substantial immune response that was comparable between SC and IM subjects, but local reactogenicity may be greater for SC.

We investigated a protein-based nontypeable Haemophilus influenzae (NTHi) and pneumococcal (HiP) vaccine containing pneumococcal histidine triad D (PhtD), detoxified pneumolysin (dPly), and NTHi protein D (PD) in adults. In a phase I study, 40 healthy 18- to 40-year-old subjects were randomized (2: 2: 1) to receive two HiP doses administered 60 days apart, with or without AS03 adjuvant (HiP-AS and HiP groups, respectively), or Engerix B (GlaxoSmithKline, Belgium) as a control. Safety, antibodies, and antigen-specific CD4(+) T-cell immune responses were assessed before and until 480 days after vaccination. No serious adverse events were reported, and no subject withdrew due to an adverse event. Local and systemic symptoms were reported more frequently in the HiP-AS group than in the other two groups. The frequency and intensity of local and systemic symptoms appeared to increase after the second dose of HiP-AS or HiP but not Engerix B. Antibody geometric mean concentrations (GMCs) for PhtD, dPly, and PD increased after each dose of HiP-AS or HiP, with higher GMCs being observed in the HiP-AS group (statistically significant for anti-PD after dose 1 and anti-Ply after dose 2). GMCs remained higher at day 420 than prior to vaccination in both the HiP-AS and HiP groups. Antigen-specific CD4(+) T cells increased after each dose but were un-measurable by day 480. Two doses of an investigational PhtD-dPly-PD protein vaccine induced humoral immunity and antigen-specific CD4(+) T-cell responses after each dose, with generally higher responses when the vaccine was administered with AS03. HiP combined with AS03 appeared to be more reactogenic than the antigens alone. (This study has been registered at ClinicalTrials.gov under registration no. NCT00814489.)

ABSTRACT Six vaccine formulations containing AS02 V or alum (aluminum phosphate [AlPO 4 ]) adjuvant with pneumococcal proteins, pneumococcal histidine triad D (PhtD), and/or detoxified pneumolysin (dPly), either as a polysaccharide carrier in an 8-valent pneumococcal conjugate vaccine (8PCV) or as free (unconjugated) proteins, were evaluated in adults -65 to 85 years of age. In this phase I observer-blind study, 167 healthy subjects were randomized to receive two doses (days 0 and 60) of 10 or 30 μg PhtD-dPly plus AS02 V or alum, 8PCV plus AS02 V or alum, or one dose (day 0) of 23-valent polysaccharide pneumococcal vaccine (23PPV) as a control (placebo on day 60). The safety, reactogenicity, and antibody-specific responses to these vaccines were evaluated. No vaccine-related serious adverse events were reported. The incidences of solicited local and specific general (fatigue and myalgia) symptoms tended to be higher in the AS02 V groups than in other groups. Anti-PhtD and anti-Ply antibody responses were observed in all groups except the control group. One month post-dose 2, the anti-PhtD and anti-Ply antibody geometric mean concentrations tended to be higher with AS02 V than with alum, higher with a dose of 30 μg than with 10 μg for PhtD-dPly and higher with 30-μg PhtD-dPly formulations than with conjugated PhtD and dPly (8PCV) formulations. Functional antibody responses, measured by an opsonophagocytic activity assay, tended to be higher with 8PCV than with 23PPV. In conclusion, vaccine formulations containing free or conjugated PhtD and dPly had acceptable reactogenicity and safety profiles in elderly adults. Immune responses were enhanced with an AS02 V -adjuvanted formulation containing free 30-μg PhtD-dPly compared to those with alum adjuvant and conjugated proteins. (This study has been registered at ClinicalTrials.gov under registration no. NCT00756067.)

Published Ahead of Print 30 October 2013. 10.1128/CVI.00430-13. 2014, 21(1):56. DOI: Clin. Vaccine Immunol. Pascal Lestrate and Dominique Boutriau Johan Berglund, Peter Vink, Fernanda Tavares Da Silva, Controlled Study in Healthy Adults Vaccine in a Phase 1 Randomized Haemophilus influenzae Triple-Protein Streptococcus pneumoniae and Persistence following an Investigational Safety, Immunogenicity, and Antibody

In the Netherlands, bacterial canker in plum trees (Prunus domestica) is a serious and recent problem in plum production. Bacterial canker, caused by Pseudomonas syringae pv. syringae (Pss) and pv. morsprunorum (Psm), is a serious disease of stone fruit, and occurs in all major stone fruit producing areas of the world. The trunks of the affected plum trees are girdled by bacterial cankers resulting in sudden death of infected trees. Rapid tree death has been observed in several orchards 2-4 years after planting. Disease incidences can be very high, and sometimes complete orchards have to be removed. Recently, plum cultivation in the Netherlands has changed from a relatively extensive into an intensive cultivation. This was made possible by the use of a weak rootstock, Krymsk (R) 1 (VVA-1). The lack of chemicals to fight bacterial diseases in the orchards created a need for alternative methods of disease control. To achieve this, methods such as prevention, biological control and plant resistance must be explored and control strategies to manage plum decline have to be developed. In 2010 a project was started to study the epidemiology and possible control of plum decline.

Bij de teelt van verschillende bol- en knolgewassen kunnen ziekten door sclerotievormende schimmels zoals Sclerotinia bulborum, Sclerotinia tuberosa en Sclerotium rolfsii voor veel uitval zorgen. Tot nu toe konden de genoemde schimmels redelijk tot goed worden onderdrukt met middelen als procymidon (Sumisclex) en tolclofos-methyl (Rizolex). Echter deze fungiciden zijn niet meer toepasbaar of worden in de toekomst waarschijnlijk niet meer toepasbaar. Daarom is het noodzakelijk dat naar andere vormen van bestrijding wordt gezocht. Op dit moment zijn er goede ervaringen met de bestrijding en onderdrukking van sclerotievormende schimmels bij de teelt van groenten met het middel Contans. Dit middel werkt op basis van de schimmel Coniohyrium minitans die als een antagonist optreedt tegen bijv. de schimmel Sclerotinia. De vraag was of dit middel ook is toe te passen bij de beheersing van schimmelziekten door sclerotievormende schimmels in bolgewassen.