Magrolimab Plus Rituximab in Relapsed/Refractory Indolent Non-Hodgkin Lymphoma: Phase 1/2 Trial 3-Year Follow-up.

Relapsed/refractory (R/R) indolent non-Hodgkin lymphoma (iNHL) is generally considered incurable with current treatment options. Previous phase 1b/2 results showed combining the anti-cluster-of-differentiation (CD) 47 activity of magrolimab with the anti-CD20 activity of rituximab (M+R) has antitumor activity against R/R iNHL. Here, we report 3-year follow-up data from this phase 1b/2 study (NCT02953509) assessing long-term safety and efficacy of M+R in R/R iNHL. After magrolimab priming, 4 groups of phase 1b M+R patients received 10-45 mg/kg magrolimab maintenance doses with 375 mg/m2 rituximab. Phase 2 explored 30 and 45 mg/kg magrolimab. Primary endpoints were treatment-emergent adverse events (TEAEs) and objective response rate (ORR). Secondary endpoints included duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Exploratory analysis included assessment of circulating tumor DNA, biomarkers of magrolimab tumor penetration, and drug target expression. Of 46 patients treated in phase 1b/2, 42 had follicular lymphoma and 4 had marginal zone lymphoma. All patients experienced ≥1 any-grade TEAE, and 44 reported ≥1 treatment-related TEAE. No additional toxicities were reported during long-term follow-up, and there were no treatment-related deaths. Median follow-up was 36.7 (range, 1.2-62.3) months. The ORR was 52.2%, with 30.4% achieving a complete response. The median DOR was 15.9 (95% CI, 5.6-not estimable) months. The median time-to-response was 1.8 (range, 1.6-5.5) months; median PFS and OS were 7.4 (95% CI, 4.8-13.0) months and not reached, respectively. These results demonstrate the long-term safety and efficacy of M+R in patients with iNHL and support further exploration of CD47-based treatment combinations.

The PI3Kδ inhibitor zandelisib on intermittent dosing in relapsed/refractory follicular lymphoma: Results from a global phase 2 study.

In this global phase 2 study in patients with relapsed/refractory follicular lymphoma (FL), zandelisib was administered on intermittent dosing to mitigate immune-related adverse events and infections that have been reported with oral PI3Kδ inhibitors administered daily continuously. Eligible patients with measurable disease and progression after at least two prior therapies were administered zandelisib until disease progression or intolerability. The primary efficacy endpoint was objective response rate (ORR) and the key secondary efficacy endpoint was duration of response (DOR). We report on 121 patients with FL administered zandelisib on intermittent dosing after 8 weeks of daily dosing for tumor debulking. The median number of prior therapies was 3 (range, 2-8) and 45% of patients had refractory disease. The ORR was 73% (95% confidence interval [CI], 63.9-80.4), the complete response (CR) rate was 38% (95% CI, 29.3-47.3), and the median DOR was 16.4 months (95% CI, 9.5-not reached). With a median follow-up of 14.3 months (range, 1-30.5), the median progression-free survival was 11.6 months (95% CI, 8.3-not reached). Twenty-one patients (17%) discontinued therapy due to an adverse event. Grade 3-4 class-related toxicities included 6% diarrhea, 5% lung infections, 3% colitis (confirmed by biopsy or imaging), 3% rash, 2% AST elevation, and 1% non-infectious pneumonitis. Zandelisib achieved a high rate of durable responses in heavily pretreated patients with relapsed/refractory FL. The intermittent dosing resulted in a relatively low incidence of severe class-related toxicities, which supports the evaluation of zandelisib as a single agent and in combination with indolent B-cell malignancies.

Surgical reconstruction of a composite nasomaxillary and superior labial defect in a dog with a fascia lata graft, titanium mesh implant and angularis oris axial pattern flap.

Objective: To document the successful surgical reconstruction of a composite nasomaxillary and superior labial defect using a fascia lata graft, titanium mesh and angularis oris axial pattern flap in a dog. Case summary: An estimated 2-year-old female intact mixed-breed dog was presented with a composite (hard and soft tissue) nasomaxillary defect, suspected to be caused by a chemical burn. Physical examination revealed nasal discharge, exposed bilateral maxilla and nasal bone, nasomaxillary fistula with air movement, and intrinsic discoloration of the left maxillary canine tooth. The soft tissue lesion extended from the nasal planum rostrally to the medial canthus of the left eye distally and from the right maxillary bone to include a full thickness loss of the left maxillary labium laterally. Computed tomographic images of the head showed chronic osteomyelitis of the maxilla, zygomatic and nasal bones with nasomaxillary fistula and numerous exposed roots of the left maxillary premolars. Staged surgical procedures to address the dentition and nasomaxillary defect were planned. The first procedure consisted of the extraction of periodontally compromised left maxillary premolars, and standard root canal therapy of bilateral maxillary canine teeth. The second procedure consisted of debridement of the non-vital soft and hard tissues and surgical reconstruction of the nasomaxillary defect after virtual surgical planning. Head computed tomography performed 5 months post-operatively revealed a decrease in the size of the osseous defect as well as the resolution of rhinitis. Clinical relevance: This case demonstrates the feasibility of using a combination of soft tissue graft, titanium mesh, and axial pattern flap in managing nasomaxillary defects. Such defects can lead to chronic rhinitis, infection, discomfort, and long-term morbidity. This case report provides a novel but practical approach for managing defects in the nasomaxillary region in dogs.

Mitochondrial bioenergetics are not associated with myofibrillar protein synthesis rates.

BACKGROUND: Mitochondria represent key organelles influencing cellular homeostasis and have been implicated in the signalling events regulating protein synthesis. METHODS: We examined whether mitochondrial bioenergetics (oxidative phosphorylation and reactive oxygen species (H2O2) emission, ROS) measured in vitro in permeabilized muscle fibres represent regulatory factors for integrated daily muscle protein synthesis rates and skeletal muscle mass changes across the spectrum of physical activity, including free-living and bed-rest conditions: n = 19 healthy, young men (26 ± 4 years, 23.4 ± 3.3 kg/m2) and following 12 weeks of resistance-type exercise training: n = 10 healthy older men (70 ± 3 years, 25.2 ± 2.1 kg/m2). Additionally, we evaluated the direct relationship between attenuated mitochondrial ROS emission and integrated daily myofibrillar and sarcoplasmic protein synthesis rates in genetically modified mice (mitochondrial-targeted catalase, MCAT). RESULTS: Neither oxidative phosphorylation nor H2O2 emission were associated with muscle protein synthesis rates in healthy young men under free-living conditions or following 1 week of bed rest (both P > 0.05). Greater increases in GSSG concentration were associated with greater skeletal muscle mass loss following bed rest (r = -0.49, P < 0.05). In older men, only submaximal mitochondrial oxidative phosphorylation (corrected for mitochondrial content) was positively associated with myofibrillar protein synthesis rates during exercise training (r = 0.72, P < 0.05). However, changes in oxidative phosphorylation and H2O2 emission were not associated with changes in skeletal muscle mass following training (both P > 0.05). Additionally, MCAT mice displayed no differences in myofibrillar (2.62 ± 0.22 vs. 2.75 ± 0.15%/day) and sarcoplasmic (3.68 ± 0.35 vs. 3.54 ± 0.35%/day) protein synthesis rates when compared with wild-type mice (both P > 0.05). CONCLUSIONS: Mitochondrial oxidative phosphorylation and reactive oxygen emission do not seem to represent key factors regulating muscle protein synthesis or muscle mass regulation across the spectrum of physical activity.

High HTLV-1 Proviral Load Predates and Predicts HTLV-1-Associated Disease: Literature Review and the London Experience.

Human T cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that infects lymphocytes and causes severe diseases. HTLV-1 proviral load (PVL), i.e., the number of host cells that carry HTLV-1 proviral DNA integrated into their genome, can be measured in peripheral blood mononuclear cells (PBMCs) using quantitative polymerase chain reaction. In this narrative review, we discuss the usefulness of HTLV-1 PVL quantification and share our experience acquired during more than 30 years of follow-up of people living with HTLV-1 in the UK. Patients with HTLV-1-associated myelopathy have higher PVL than those with asymptomatic infection. This is consistent across studies in different countries. High PVL predates symptom onset for both inflammatory and proliferative diseases. High PVL is essential but not sufficient for the development of HTLV-1-associated diseases. Therefore, PVL quantification can be used to support the care of people living with HTLV-1 by identifying those most at risk of HTLV-1-associated diseases.

A diverse set of Enterococcus-infecting phage provides insight into phage host-range determinants.

Enterococci are robust Gram-positive bacteria that pose a significant threat in healthcare settings due to antibiotic resistance, with vancomycin-resistant enterococci (VRE) most prominent. To tackle this issue, bacteriophages (bacterial viruses) can be exploited as they specifically and efficiently target bacteria. Here, we successfully isolated and characterised a set of novel phages: SHEF10, SHEF11, SHEF13, SHEF14, and SHEF16 which target E. faecalis (SHEF10,11,13), or E. faecium (SHEF13, SHEF14 & SHEF16) strains including a range of clinical and VRE isolates. Genomic analysis shows that all phages are strictly lytic and diverse in terms of genome size and content, quickly and effectively lysing strains at different multiplicity of infections. Detailed analysis of the broad host-range SHEF13 phage revealed the crucial role of the enterococcal polysaccharide antigen (EPA) variable region in its infection of E. faecalis V583. In parallel, the discovery of a carbohydrate-targeting domain (CBM22) found conserved within the three phage genomes indicates a role in cell surface interactions that may be important in phage-bacterial interactons. These findings advance our comprehension of phage-host interactions and pave the way for targeted therapeutic strategies against antibiotic-resistant enterococcal infections.

Brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma in the United Kingdom: A real-world intention-to-treat analysis.

Brexucabtagene autoleucel (brexu-cel) is an autologous CD19 CAR T-cell product, approved for relapsed/refractory (r/r) mantle cell lymphoma (MCL). In ZUMA-2, brexu-cel demonstrated impressive responses in patients failing ≥2 lines, including a bruton's tyrosine kinase inhibitor, with an overall and complete response rate of 93% and 67%, respectively. Here, we report our real-world intention-to-treat (ITT) outcomes for brexu-cel in consecutive, prospectively approved patients, from 12 institutions in the United Kingdom between February 2021 and June 2023, with a focus on feasibility, efficacy, and tolerability. Of 119 approved, 104 underwent leukapheresis and 83 received a brexu-cel infusion. Progressive disease (PD) and/or manufacturing (MF) were the most common reasons for failure to reach harvest and/or infusion. For infused patients, best overall and complete response rates were 87% and 81%, respectively. At a median follow-up of 13.3 months, median progression-free survival (PFS) for infused patients was 21 months (10.1-NA) with a 6- and 12-month PFS of 82% (95% confidence interval [CI], 71-89) and 62% (95% CI, 49-73), respectively. ≥Grade 3 cytokine release syndrome and neurotoxicity occurred in 12% and 22%, respectively. On multivariate analysis, inferior PFS was associated with male sex, bulky disease, ECOG PS > 1 and previous MF. Cumulative incidence of non-relapse mortality (NRM) was 6%, 15%, and 25% at 6, 12, and 24 months, respectively, and mostly attributable to infection. Outcomes for infused patients in the UK are comparable to ZUMA-2 and other real-world reports. However, ITT analysis highlights a significant dropout due to PD and/or MF. NRM events warrant further attention.

Does serous tubal intraepithelial carcinoma (STIC) metastasize? The clonal relationship between STIC and subsequent high-grade serous carcinoma in BRCA1/2 mutation carriers several years after risk-reducing salpingo-oophorectomy.

OBJECTIVE: The majority of high-grade serous carcinomas (HGSC) of the ovary, fallopian tube, and peritoneum arise from the precursor lesion called serous tubal intraepithelial carcinoma (STIC). It has been postulated that cells from STICs exfoliate into the peritoneal cavity and give rise to peritoneal HGSC several years later. While co-existent STICs and HGSCs have been reported to share similarities in their mutational profiles, clonal relationship between temporally distant STICs and HGSCs have been infrequently studied and the natural history of STICs remains poorly understood. METHODS: We performed focused searches in two national databases from the Netherlands and identified a series of BRCA1/2 germline pathogenic variant (GPV) carriers (n = 7) who had STIC, and no detectable invasive carcinoma, at the time of their risk-reducing salpingo-oophorectomy (RRSO), and later developed peritoneal HGSC. The clonal relationship between these STICs and HGSCs was investigated by comparing their genetic mutational profile by performing next-generation targeted sequencing. RESULTS: Identical pathogenic mutations and loss of heterozygosity of TP53 were identified in the STICs and HGSCs of five of the seven patients (71%), confirming the clonal relationship of the lesions. Median interval for developing HGSC after RRSO was 59 months (range: 24-118 months). CONCLUSION: Our results indicate that cells from STIC can shed into the peritoneal cavity and give rise to HGSC after long lag periods in BRCA1/2 GPV carriers, and argues in favor of the hypothesis that STIC lesions may metastasize.

Biodegradable Alkali-Swellable Emulsion Polymers: Industrial and Commercial Thickeners.

Sustainability and circularity are key issues facing the global polymer industry. The search for biodegradable and environmentally-friendly polymers that can replace conventional materials is a difficult challenge that has been met with limited success. Alternatives must be cost-effective, scalable, and provide equivalent performance. We report that latexes made by the conventional emulsion polymerization of vinyl acetate and functional vinyl ester monomers are efficient thickeners for consumer products and biodegrade in wastewater. This approach uses readily-available starting materials and polymerization is carried out in water at room temperature, in one pot, and generates negligible waste. Moreover, the knowledge that poly(vinyl ester)s are biodegradable will lead to the design of new green polymer materials.

Impact and economic analysis of human T-cell lymphotropic virus type 1 (HTLV-1)-targeted antenatal screening, England and Wales, 2021.

BackgroundHuman T-cell lymphotropic virus type 1 (HTLV-1) is a neglected virus that can cause severe disease and be transmitted from mother to child through breastfeeding. Avoidance of breastfeeding prevents 80% of vertical transmission. The United Kingdom (UK) is currently assessing whether HTLV-1-targeted antenatal screening should be implemented.AimWe aimed to assess the impact and cost-effectiveness of a targeted programme to prevent HTLV-1 vertical transmission in England and Wales.MethodsWe estimated the number of pregnant women who have high risk of HTLV-1 infection based on their or their partner's country of birth. With data from 2021, we used a mathematical model to assess cost-effectiveness of HTLV-1 antenatal screening. We also estimated the annual number of infant infections and the number that could be prevented with screening and intervention.ResultsWe estimate that ca 99,000 pregnant women in England and Wales have high risk of HTLV-1 infection. In the absence of screening, 74 (range: 25-211) HTLV-1 infections in infants would be expected to occur every year in England and Wales. Implementation of targeted screening would prevent 58 (range: 19-164) infant infections annually. The intervention is effective (incremental 0.00333 quality-adjusted life years (QALY)) and cost-saving (GBP -57.56 (EUR -66.85)).ConclusionOur findings support implementation of HTLV-1 targeted antenatal screening to reduce vertical transmission from mothers to infants in the UK.

Ibrutinib as part of risk-stratified treatment for posttransplant lymphoproliferative disorder: the phase 2 TIDaL trial.

ABSTRACT: Posttransplant lymphoproliferative disorder (PTLD) is a rare complication of solid organ transplantation, and cytotoxic chemotherapy is associated with treatment-related morbidity and mortality. Current treatment takes a sequential, risk-stratified approach, and patients with low-risk disease after initial immunotherapy can avoid escalation to immunochemotherapy. TIDaL is a prospective, single-arm phase 2 trial investigating the activity and tolerability of ibrutinib combined with risk-stratified therapy for first-line treatment of PTLD. Eligible patients were adults with newly diagnosed CD20+ B-cell PTLD after solid organ transplant and performance status 0 to 2. Initial treatment comprised 49 days of ibrutinib 560 mg once daily, with 4 doses of weekly rituximab. Treatment response on interim scan and baseline International Prognostic Index were used to allocate patients to either a low-risk arm (who continued ibrutinib, alongside 4 further doses of 3-weekly rituximab) or high-risk (escalation to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP] immunochemotherapy, with ibrutinib continuing in patients aged <65 years). The primary outcome was complete response on interim scan, achieved by 11 of 38 patients (29%; 95% confidence interval [CI], 15-46). This did not reach the prespecified threshold for clinically significant activity. Secondary outcomes included allocation to the low-risk arm (41% of patients), 2-year progression-free survival (58%; 95% CI, 44-76), and 2-year overall survival (76%; 95% CI, 63-91). Adverse events were mostly hematological, gastrointestinal, and infective. Although TIDaL does not support adding ibrutinib into first-line treatment of PTLD, increasing the proportion of patients who can be treated without cytotoxic chemotherapy remains an important aim of future research. This trial was registered at www.clinicaltrials.gov as #ISRCTN32667607.

Pregnancy Management in HIV Viral Controllers: Twenty Years of Experience.

(1) Background: The evidence base for the management of spontaneous viral controllers in pregnancy is lacking. We describe the management outcomes of pregnancies in a series of UK women with spontaneous HIV viral control (<100 copies/mL 2 occasions before or after pregnancy off ART). (2) Methods: A multi-centre, retrospective case series (1999-2021) comparing pre- and post-2012 when guidelines departed from zidovudine-monotherapy (ZDVm) as a first-line option. Demographic, virologic, obstetric and neonatal information were anonymised, collated and analysed in SPSS. (3) Results: A total of 49 live births were recorded in 29 women, 35 pre-2012 and 14 post. HIV infection was more commonly diagnosed in first reported pregnancy pre-2012 (15/35) compared to post (2/14), p = 0.10. Pre-2012 pregnancies were predominantly managed with ZDVm (28/35) with pre-labour caesarean section (PLCS) (24/35). Post-2012 4/14 received ZDVm and 10/14 triple ART, p = 0.002. Post-2012 mode of delivery was varied (5 vaginal, 6 PLCS and 3 emergency CS). No intrapartum ZDV infusions were given post-2012 compared to 11/35 deliveries pre-2012. During pregnancy, HIV was detected (> 50 copies/mL) in 14/49 pregnancies (29%) (median 92, range 51-6084). Neonatal ZDV post-exposure prophylaxis was recorded for 45/49 infants. No transmissions were reported. (4) Conclusion: UK practice has been influenced by the change in guidelines, but this has had little impact on CS rates.

Systemic Inflammation, the Peripheral Blood Transcriptome, and Primary Melanoma.

Peripheral blood transcriptomes from 383 patients with newly diagnosed melanoma were subjected to differential gene expression analysis. The hypotheses were that impaired systemic immunity is associated with poorer prognosis (thicker tumors and fewer tumor-infiltrating lymphocytes) and evidence of systemic inflammation (high-sensitivity CRP and fibrinogen levels). Higher fibrinogen levels were associated with thicker primary tumors. In single-gene analysis, high-sensitivity CRP levels were significantly associated with higher blood CD274 expression (coding for PD-L1), but each was independently prognostic, with high-sensitivity CRP associated with increased mortality and higher CD274 protective, independent of age. Pathway analysis identified downregulation of immune cell signaling pathways in the blood of people with thicker tumors and notable upregulation of signal transducer and activator of transcription 1 gene STAT1 in people with brisk tumor-infiltrating lymphocytes. Transcriptomic data provided evidence for increased NF-kB signaling with higher inflammatory markers but with reduction in expression of HLA class II molecules and higher CD274, suggesting that aberrant systemic inflammation is a significant mediator of reduced immune function in melanoma. In summary, transcriptomic data revealed evidence of reduced immune function in patients with thicker tumors and fewer tumor-infiltrating lymphocytes at diagnosis. Inflammatory markers were associated with thicker primaries and independently with death from melanoma, suggesting that systemic inflammation contributes to that reduced immune function.

The first extensive analysis of species composition and abundance of stink bugs (Hemiptera: Pentatomidae) on soybean crops in Brazil.

BACKGROUND: Soybean is the third-greatest global commodity crop with respect to grain production, Brazil is the largest soybean producer in the world. We performed the first extensive survey including all the five main soybean cultivation regions in Brazil over three seasons (2018/2019, 2019/2020, and 2020/2021). A total of 2386 localities were sampled, corresponding to 145 municipalities in 11 states. Sampling was carried out between the R1 and R8 soybean growth stages, using a beating sheet. RESULTS: Fifteen species were recorded, with five species accounting for more than 99% of the sampled insects. The Neotropical brown stink bug, Euschistus heros (F.), was the most abundant species (82.4% of the adults and 84.1% of the nymphs overall), with differences in the mean abundance between soybean macroregions. The melacanthus green belly stink bug, Diceraeus melacanthus Dallas was the second most abundant species overall, followed by the brown winged stink bug, Edessa meditabunda (F.), the furcatus green belly stink bug, Diceraeus furcatus (F.) and the red-banded green stink bug, Piezodorus guildinii (Westwood). The relative abundance of each species differed between soybean macroregions. The mean abundance of nymphs and adults of Euschistus heros at different soybean reproductive stages showed an increase from early reproductive stages to the beginning of the late reproductive stages (R5 or R6). CONCLUSION: This large-scale assessment of stink bugs provides a basis for outlining integrated pest management programs and drives the development of monitoring and control strategies, as well as future studies investigating population dynamics over time and space in soybean fields. © 2024 Society of Chemical Industry.

Resistance management and integrated pest management insights from deployment of a Cry3Bb1+ Gpp34Ab1/Tpp35Ab1 pyramid in a resistant western corn rootworm landscape.

In Nebraska USA, many populations of western corn rootworm (WCR), Diabrotica virgifera virgifera LeConte, now exhibit some level of resistance to all corn rootworm-active Bacillus thuringiensis Berliner (Bt) proteins expressed in commercial hybrids. Therefore, a study was conducted in northeast Nebraska from 2020-2022 to reevaluate current corn rootworm management options in continuous maize (consecutive planting for ≥2 years). Results from on-farm experiments to evaluate a standard soil-applied insecticide (Aztec® 4.67G) in combination with non-rootworm Bt or rootworm-active Bt pyramided maize (Cry3Bb1 + Gpp34Ab1/Tpp35Ab1) are reported within the context of WCR Bt resistance levels present. Corrected survival from Bt pyramid single-plant bioassays (<0.3, 0.3-0.49, >0.5) was used to place populations into 3 resistance categories. Variables evaluated included root injury, adult emergence, proportion lodged maize, and grain yield. Key results: A composite analysis of all populations across resistance levels indicated that addition of soil insecticide to Bt pyramid significantly reduced adult emergence and lodging but did not significantly increase root protection or yield. Within and among resistance category analyses of root injury revealed that the Bt pyramid remained highly efficacious at any non-rootworm Bt root injury level when resistance was absent or low. When corrected survival was >0.3, mean Bt pyramid root injury tracked more closely in a positive linear fashion with mean non-rootworm Bt root injury (rootworm density x level of resistance interaction). Similar trends were obtained for adult emergence but not yield. Mean Bt pyramid root injury rating was <0.75 in most populations with Bt resistance, which contributed to no significant yield differences among categories. Results are discussed within the context of IPM:IRM tradeoffs and the need to reduce WCR densities in this system to decrease the impact of the density x resistance interaction to bridge use of current pyramids with new technologies introduced over the next decade.

Comprehensive Insight into the Functional Roles of NK and NKT Cells in HTLV-1-Associated Diseases and Asymptomatic Carriers.

Human T cell leukemia virus type 1 (HTLV-1) is the first human oncogenic retrovirus to be discovered and causes two major diseases: a progressive neuro-inflammatory disease, termed HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP), and an aggressive malignancy of T lymphocytes known as adult T cell leukemia (ATL). Innate and acquired immune responses play pivotal roles in controlling the status of HTLV-1-infected cells and such, the outcome of HTLV-1 infection. Natural killer cells (NKCs) are the effector cells of the innate immune system and are involved in controlling viral infections and several types of cancers. The ability of NKCs to trigger cytotoxicity to provide surveillance against viruses and cancer depends on the balance between the inhibitory and activating signals. In this review, we will discuss NKC function and the alterations in the frequency of these cells in HTLV-1 infection.

Diverse genetic basis of Vip3Aa resistance in five independent field-derived strains of Helicoverpa zea in the US.

BACKGROUND: Practical resistance of Helicoverpa zea to Cry proteins has become widespread in the US, making Vip3Aa the only effective Bacillus thuringiensis (Bt) protein for controlling this pest. Understanding the genetic basis of Vip3Aa resistance in H. zea is essential in sustaining the long-term efficacy of Vip3Aa. The objectives of this study were to characterize the inheritance of Vip3Aa resistance in four distinct field-derived H. zea strains (M1-RR, AC4-RR, R2-RR and R15-RR), and to test for shared genetic basis among these strains and a previously characterized Texas resistant strain (LT#70-RR). RESULTS: Maternal effects and sex linkage were absent, and the effective dominance level (DML) was 0.0 across Vip3Aa39 concentrations ranging from 1.0 to 31.6 µg cm-2, in all H. zea resistant strains. Mendelian monogenic model tests indicated that Vip3Aa resistance in each of the four strains was controlled by a single gene. However, interstrain complementation tests indicated that three distinct genetic loci are involved in Vip3Aa resistance in the five resistant H. zea strains: one shared by M1-RR and LT#70-RR; another shared by R2-RR and R15-RR; and a distinct one for AC4-RR. CONCLUSION: Results of this study indicate that Vip3Aa resistance in all H. zea strains was controlled by a single, recessive and autosomal gene. However, there were three distinct genetic loci associated with Vip3Aa resistance in the five resistant H. zea strains. The information generated from this study is valuable for exploring mechanisms of Vip3Aa resistance, monitoring the evolution of Vip3Aa resistance, and devising effective strategies for managing Vip3Aa resistance in H. zea. © 2024 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.