Candidate Vectors Research Articles

Determining the Minimally Effective Dose of a Clinical Candidate AAV Vector in a Mouse Model of Crigler-Najjar Syndrome

Liver metabolism disorders are attractive targets for gene therapy, because low vector doses can reverse the buildup of toxic metabolites in the blood. Crigler-Najjar syndrome is an inherited disorder of bilirubin metabolism that is caused by the absence of uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) activity. This syndrome is characterized by hyperbilirubinemia and jaundice. Unfortunately, current phototherapy treatment is not effective long term. We intravenously injected phototherapy-rescued adult UGT1 knockout mice with 2.5 × 1010–2.5 × 1013 genome copies (GC)/kg of a clinical candidate vector, AAV8.TBG.hUGT1A1co, to study the treatment of disease compared to vehicle-only control mice. There were no apparent vector-related laboratory or clinical sequelae; the only abnormalities in clinical pathology were elevations in liver transaminases, primarily in male mice at the highest vector dose. Minimal to mild histopathological findings were present in control and vector-administered male mice. At vector doses greater than 2.5 × 1011 GC/kg, we observed a reversal of total bilirubin levels to wild-type levels. Based on a significant reduction in serum total bilirubin levels, we determined the minimally effective dose in this mouse model of Crigler-Najjar syndrome to be 2.5 × 1011 GC/kg.

Physical Characterization and Stabilization of a Lentiviral Vector Against Adsorption and Freeze-Thaw

A replication-deficient lentiviral vector encoding the tumor antigen gene NY-ESO-1 was characterized in terms of vector morphology, particle size range, concentration, and zeta potential using a variety of physical methods. Environmentally stressed vector samples were then evaluated in terms of viral vector particle size and concentration by nanoparticle tracking analysis (NTA). These NTA stability results correlated reasonably well with a quantitative polymerase chain reaction assay for quantitation of viral genome copy number (r2 = 0.80). Approximately 40 pharmaceutical excipients were examined for their ability to stabilize the vector against exposure to an adsorptive container surface (glass) as well as freeze-thaw cycling using NTA as the screening method. Stabilizing additives that inhibited viral vector particle loss under these conditions included proline, lactose, and mannitol. Several candidate frozen liquid formulations that contained a combination of these lead excipients and various buffering agents were further evaluated for their ability to stabilize the viral vector. The additional benefit of lowering the Tris buffer concentration was observed. This study highlights the use of physical particle assays such as NTA for initial screening of stabilizing excipients to minimize vector loss due to container adsorption and freeze-thaw cycling to facilitate early formulation development of viral vector candidates in frozen liquid formulations.

Killing boundary data for anti-de Sitter-like spacetimes

Given an initial-boundary value problem for an anti-de Sitter-like spacetime, we analyse conditions on the conformal boundary ensuring the existence of Killing vectors in the arising spacetime. This analysis makes use of a system of conformal wave equations describing the propagation of the Killing equation first considered by Paetz. We identify an obstruction tensor constructed from Killing vector candidate and the Cotton tensor of the conformal boundary whose vanishing is a necessary condition for the existence of Killing vectors in the spacetime. This obstruction tensor vanishes if the conformal boundary is conformally flat.

A Low Complexity Reactive Tabu Search Based Constellation Constraints in Signal Detection

For Massive multiple-input multiple output (MIMO) systems, many algorithms have been proposed for detecting spatially multiplexed signals, such as reactive tabu search (RTS), minimum mean square error (MMSE), etc. As a heuristic neighborhood search algorithm, RTS is particularly suitable for signal detection in systems with large number of antennas. In this paper, we propose a strategy to reduce the neighborhood searching space of the traditional RTS algorithms. For this, we introduce a constellation constraints (CC) structure to determine whether including a candidate vector into the RTS searching neighborhood. By setting a pre-defined threshold on the symbol constellation, the Euclidean distance between the estimated signal and its nearest constellation points are calculated, and the threshold and distance are compared to separate the reliable estimated signal from unreliable ones. With this structure, the proposed CC-RTS algorithm may ignore a significant number of unnecessary candidates in the RTS neighborhood searching space and greatly reduce the computational complexity of the traditional RTS algorithm. Simulation results show that the BER performance of the proposed CC-RTS algorithm is very close to that of the traditional RTS algorithm, and with about 50% complexity reduction with the same signal-to-noise (SNR) ratio.

Improved immune response against HIV-1 Env antigen by enhancing EEV production via a K151E mutation in the A34R gene of replication-competent vaccinia virus Tiantan

The development of an effective HIV-1 vaccine is still a global priority. In recent years, vaccinia virus (VV) has been widely used as an HIV-1 vaccine vector, but its immune efficacy against HIV-1 antigens needs to be optimized. The extracellular enveloped virus (EEV) of VV is capable of faster entry, earlier release, and long-range dissemination. We hypothesized that an improvement in EEV formation by the manipulation of VV genes involved in the EEV release would consequently cause an improved expression of the VV carrying HIV-1 Env antigen and a subsequent enhanced immune response. To this end, an A34R K151E mutant (rVTT-A34Rmut) from VV Tiantan strain (VTT) with robustly increased EEV release was selected to serve as an optimized vaccine vector. The results were consistent with our hypothesis: the A34R mutant-based HIV-1 vaccine candidate rVTT-A34Rmut-Env produced more HIV-1 Env antigen in vitro and in vivo, and thus led to an improved HIV-1 Env-specific T cell immune response, binding antibody, and even the neutralizing antibody response in mice without increased virulence. Meanwhile, the application of the A34R mutation on another VV-based HIV-1 vaccine candidate, VTKgpe, also exhibited a similar immune enhancement effect with no enhanced virulence. The results in this study suggested that rVTT-A34Rmut is a potentially improved vaccine vector candidate for human application. In addition, the improvement of the EEV formation via the A34R gene mutation may also be potent in other poxvirus vector-based vaccines against HIV-1 or other pathogens and even cancer in the future.

Improved Finite-Control-Set Model Predictive Control for Cascaded H-Bridge Inverters

In multilevel cascaded H-bridge (CHB) inverters, the number of voltage vectors generated by the inverter quickly increases with increasing voltage level. However, because the sampling period is short, it is difficult to consider all the vectors as the voltage level increases. This paper proposes a model predictive control algorithm with reduced computational complexity and fast dynamic response for CHB inverters. The proposed method presents a robust approach to interpret a next step as a steady or transient state by comparing an optimal voltage vector at a present step and a reference voltage vector at the next step. During steady state, only an optimal vector at a present step and its adjacent vectors are considered as a candidate-vector subset. On the other hand, this paper defines a new candidate vector subset for the transient state, which consists of more vectors than those in the subset used for the steady state for fast dynamic speed; however, the vectors are less than all the possible vectors generated by the CHB inverter, for calculation simplicity. In conclusion, the proposed method can reduce the computational complexity without significantly deteriorating the dynamic responses.

Reduction of Computational Efforts in Finite Element-Based Permanent Magnet Traction Motor Optimization

This paper presents a method for reducing computational time in constrained single objective optimization problems related to permanent magnet motors modeled using computationally intensive finite element method. The method is based on differential evolution algorithm. The principal approach is to interrupt the evaluation of inequality constraints after encountering the constraint which is violated and continue their evaluation only if better solutions are obtained in comparison with the candidate vector from the previous generation both in terms of inequality constraints and the cost function. This approach avoids unnecessary time consuming finite element calculations required for solving the inequality constraints and saves the overall optimization time without affecting the convergence rate. The main features of this approach and how it complements the existing method for handling inequality constraints in Differential Evolution algorithm is demonstrated on design optimization of an interior permanent magnet motor for the low-floor tram TMK 2200. The motor geometry is optimized for maximum torque density.

Amblyomma americanum (Acari: Ixodidae) Ticks Are Not Vectors of the Lyme Disease Agent, Borrelia burgdorferi (Spirocheatales: Spirochaetaceae): A Review of the Evidence.

In the early 1980s, Ixodes spp. ticks were implicated as the key North American vectors of Borrelia burgdorferi (Johnson, Schmid, Hyde, Steigerwalt and Brenner) (Spirocheatales: Spirochaetaceae), the etiological agent of Lyme disease. Concurrently, other human-biting tick species were investigated as potential B. burgdorferi vectors. Rashes thought to be erythema migrans were observed in patients bitten by Amblyomma americanum (L.) (Acari: Ixodidae) ticks, and spirochetes were visualized in a small percentage of A. americanum using fluorescent antibody staining methods, sparking interest in this species as a candidate vector of B. burgdorferi. Using molecular methods, the spirochetes were subsequently described as Borrelia lonestari sp. nov. (Spirocheatales: Spirochaetaceae), a transovarially transmitted relapsing fever Borrelia of uncertain clinical significance. In total, 54 surveys from more than 35 research groups, involving more than 52,000 ticks, have revealed a low prevalence of B. lonestari, and scarce B. burgdorferi, in A. americanum. In Lyme disease-endemic areas, A. americanum commonly feeds on B. burgdorferi-infected hosts; the extremely low prevalence of B. burgdorferi in this tick results from a saliva barrier to acquiring infection from infected hosts. At least nine transmission experiments involving B. burgdorferi in A. americanum have failed to demonstrate vector competency. Advancements in molecular analysis strongly suggest that initial reports of B. burgdorferi in A. americanum across many states were misidentified B. lonestari, or DNA contamination, yet the early reports continue to be cited without regard to the later clarifying studies. In this article, the surveillance and vector competency studies of B. burgdorferi in A. americanum are reviewed, and we conclude that A. americanum is not a vector of B. burgdorferi.

Characterizing the effects of insertion of a 5.2 kb region of a VACV genome, which contains known immune evasion genes, on MVA immunogenicity

Modified Vaccinia virus Ankara (MVA) is an attenuated Vaccinia virus (VACV) that is a popular vaccine vector candidate against many different pathogens. Its replication-restricted nature makes it a safe vaccine. However, higher doses or multiple boosts of MVA are necessary to elicit an immune response similar to wild-type VACV. Multiple strategies have been used to create modified MVA viruses that remain safe, but have increased immunogenicity. For example, one common strategy is to delete MVA immunomodulatory proteins in hopes of increasing the host immune response. Here, we take the opposite approach and examine, for the first time, how re-introduction of a 5.2 kb region of VACV DNA (that codes for multiple immunomodulatory proteins) into MVA alters viral immunogenicity. Since antigen presenting cells (APCs) are critical connectors between the innate and adaptive immune system, we examined the effect of MVA/5.2 kb infection in these cells in vitro. MVA/5.2 kb infection decreased virus-induced apoptosis and virus-induced NF-κB activation. MVA.5.2 kb infection decreased TNF production. However, MVA/5.2 kb infection did not alter APC maturation or IL-6 and IL-8 production in vitro. We further explored MVA/5.2 kb immunogenicity in vivo. VACV-specific CD8+ T cells were decreased after in vivo infection with MVA/5.2 kb versus MVA, suggesting that the MVA/5.2 kb construct is less immunogenic than MVA. These results demonstrate the limitations of in vitro studies for predicting the effects of genetic manipulation of MVA on immunogenicity. Although MVA/5.2 kb did not enhance MVA’s immunogenicity, this study examined an unexplored strategy for optimizing MVA, and the insight gained from these results can help direct how to modify MVA in the future.

Bit error rate minimisation using SLM technique in TFT-OFDM for mobile large-scale MIMO systems

In the case of large-scale Multiple-Input Multiple-Output (MIMO) systems, the Time-Frequency Training (TFT) of OFDM and their transmission schemes can solve the high-dimensional problems of channel estimation in the wireless communication systems. In the wireless technologies, their physical layer can carry out the process of transmission inside the variable channels. The noise that was induced by these channels may also degrade the performance of the system that concerns Bit Error Rate (BER). So, in this paper, a Selection Mapping (SLM) technique in the TFT-OFDM for the mobile large-scale MIMO systems has been proposed for minimising the BER. This SLM technique tends to produce the data with these phase vectors for discovering the candidate vectors and also the IFFT operation which is done on the TFT-OFDM symbol that obtains a minimum BER that has to be transmitted. This scheme performance has been compared with that of the existing TDM-OFDM with BER. The performance analysis of MIMO TFT-OFDM is considered for biomedical signal transmission through high-speed wireless transmission. The results of this experiment prove that the proposed scheme achieves a better performance than that of the existing schemes.

Presence of 16SrIV phytoplasmas of subgroups A, D and E in planthopper Haplaxius crudus Van Duzee insects in Yucatán, Mexico.

The present study was carried out to determine if group 16SrIV phytoplasmas, causing lethal yellowing (LY) disease, are present in Haplaxius crudus Van Duzee (Hemiptera: Cixiidae) insects associated with palms in Yucatán, Mexico. Haplaxius crudus feral insects were captured from palm foliage at two locations (Chicxulub Puerto and CICY, Mérida, where LY-type diseases are active) and evaluated individually for the presence of phytoplasma DNA by a group 16SrIV-specific nested PCR assay. The results showed positive detection in H. crudus insects in a proportion of 2.7% (of the total 2726 analyzed) during a 3-year period of study. The percentage of detection was different for each site, 5.9% positive of 799 insects from Mérida and 1.7% of 1927 from Chicxulub Puerto. Positive detections were also obtained in extracts from 5.3 to 1.2% of males and females, respectively. Sequencing and in silico RFLP and phylogenetic analyses of PCR-amplified rDNA products indicated that H. crudus insects from Chicxulub Puerto harbored phytoplasma strains of subgroups 16SrIV-A or 16SrIV-D, whereas in insects from Mérida the strains found were 16SrIV-A, 16SrIV-D or 16SrIV-E. The diversity of subgroup strains detected in H. crudus coincided with strains previously identified in palms showing LY-type disease syndromes in Yucatán thereby implicating H. crudus as a candidate vector of 16SrIV phytoplasmas in this region of Mexico.

МЕТОД ГЕНЕРИРОВАНИЯ ДВУМЕРНОГО БИНАРНОГО СЛУЧАЙНОГО ПРОЦЕССА

The PURPOSE of the study is search for new and modernization of known generation methods of random processes with specified static (probability distribution law) and dynamic (correlation function) probabilistic properties. METHODS. The main research methods used in the study are the probability theory, mathematical statistics and numerical methods. RESULTS. The object of the study is a permutational technology of random process generation with a simultaneously specified probability distribution law and an autocorrelation function. This technology is simple in software implementation, has high response speed and allows to introduce the required probability properties with the accuracy of their reflection, sufficient for engineering applications (e.g. in simulation modeling). The Bernoulli (binary) law is taken as a law of probability distribution of the generated process. The conducted analysis of the probabilistic properties of the behavior of the permutation procedure components has resulted in the identification of new, previously unknown functional capabilities of this method of random process generation. Probabilistic properties (probability distribution laws and autocorrelation functions of the candidate vector components) are systematized depending on a mathematically justified permutation variant. The study is given to two variants of the permutational method that allows to generate a periodically correlated binary process. It is proved that these variants simultaneously provide the possibility to generate a two-dimensional binary random process. CONCLUSION. Conducted theoretical studies allowed to expand the functionalities of the permutational procedure of binary random process generation due to the possibility to generate a two-dimensional random binary process.

Precise Positioning in Alpine Areas with Troposphere and Multipath Estimation

Real-time kinematic (RTK) positioning with Global Navigation Satellite System (GNSS) signals is widely used, e.g., for surveying, agriculture, and potentially for autonomous vehicles and unmanned air vehicles in the future. In this paper, an extended RTK positioning for significant height differences between two low-cost GNSS receivers with patch antennas is presented. In this case, the classical model for double difference measurements needs to be extended, i.e., a differential tropospheric zenith delay and pseudorange multipath errors need to be estimated besides the baseline and carrier phase integer ambiguities. The increased number of unknowns results in an ill-conditioned system of observation equations and a substantial correlation between the state estimates. We introduce prior information on the differential tropospheric zenith delay based on the differential air pressure and exploit the temporal correlation of pseudorange multipath errors. Moreover, a criterion for the integer ambiguity candidate vector selection is provided, which is robust over phase multipath and unavoidable errors in the float ambiguity covariance matrix. The proposed method is validated with two low-cost GNSS modules that were placed at the Zugspitzplatt (2601 m a.s.l.) and Eibsee (1018 m a.s.l.). The obtained estimates for the baseline and differential tropospheric zenith delay show a high repeatability over several independent ambiguity fixings. The residuals of the fixed carrier phase measurements are within 2 cm for almost all satellites, which confirms both the measurement model and the ambiguity fixing.

Subset Vector Perturbation Pre-Coding for MU-MIMO Downlink Systems

Multi-user multiple input multiple output (MU-MIMO) is a basic technique which has been widely investigated for its ability to increase system capacity. However, the inter-user interference (IUI) is one of the obstacles to obtain system capacity. With the help of pre-coding technique, the IUI can be canceled or reduced at the base station (BS). Vector perturbation (VP) is one of the most celebrated pre-coding schemes that can approach system capacity. By perturbing users’ data vector with a certain integer vector offset at the BS, the VP scheme can offer the users a higher effective signal-to-noise ratio. To reach the theory bound of VP, the BS has to select the optimal integer vector from all candidate integer vectors globally. This exhaustive search has been proved to be NP-hard, which is hard to be implemented. In this paper, we analyze several state-of-the-art modified low-complexity VP schemes and propose the subset VP (SVP) scheme to reduce the complexity of the VP. The basic principle of the SVP is that some vectors are selected as the optimal vector with high probability, whereas the others are scarcely selected. So, we try to form a subset consists of vectors with a relatively higher probability. First, we calculate the probability of all candidate vectors which have been selected as the optimal vector. Second, we propose a method to divide all vectors into several subgroups. Vectors in the same subgroup have a similar probability, whereas vectors in different subgroups have distinguished probability. Third, we build a subset that is comprised of several subgroups in which vectors have a relatively higher probability. Simulation results show that we get almost the same bit-error rate performance with a significant complexity reduction.

Hierarchical Motion Estimation for Small Objects in Frame-Rate Up-Conversion

Block-based hierarchical motion estimations are widely used for frame interpolation in frame-rate up-conversion and are successful in generating high-quality interpolations. However, it still fails in the motion estimation of small objects when a background region moves in a different direction. This is because the motion of small objects is neglected by the down-sampling and over-smoothing operations at the top level of image pyramids in the maximum a posterior (MAP) method. Consequently, the motion vector of small objects cannot be detected at the bottom level, and therefore, the small objects often appear deformed in an interpolated frame. This paper proposes a novel algorithm that preserves the motion vector of the small objects by adding a secondary motion vector candidate that represents the movement of the small objects. This additional candidate always propagates from the top to the bottom layers of the image pyramid. Experimental results demonstrate that the intermediate frame interpolated by the proposed algorithm significantly improves the visual quality when compared with conventional MAP-based frame interpolation.

Analytical Solutions for Impulsive Elliptic Out-of-Plane Rendezvous Problem via Primer Vector Theory

This paper focuses on the fixed-time minimum-fuel out-of-plane (OOP) rendezvous between close elliptic orbits of an active spacecraft, with a passive target spacecraft, assuming a linear impulsive setting. It is shown that the OOP elliptic relative dynamics are simple enough to allow for an analytical solution of the problem reviewed. Indeed, the approach relies on the primer vector theory by writing down and directly solving the optimality necessary conditions. After analyzing the characteristics of the dynamics of the optimal primer vector candidates, the complete analytical optimal solution is obtained for arbitrary durations of the rendezvous and arbitrary boundary conditions.

A propeptide toolbox for secretion optimization of Flavobacterium meningosepticum endopeptidase in Lactococcus lactis

BackgroundLactic acid bacteria are a family of “generally regarded as safe” organisms traditionally used for food fermentation. In recent years, they have started to emerge as potential chassis for heterologous protein production. And more recently, due to their beneficial properties in the gut, they have been examined as potential candidates for mucosal delivery vectors, especially for acid-sensitive enzymes. One such application would be the delivery of gluten-digesting endopeptidases for the treatment of celiac disease. To facilitate these applications, an efficient recombinant protein expression toolbox is required, especially for recombinant protein secretion. While current tools for enhancing protein secretion consist mainly of signal peptides, secretion propeptides have also been observed to play a crucial role for protein secretion and improved yields.ResultsTo expand the propeptide library for secretion optimization, we have mined and characterized three naturally occurring propeptides from the sequenced genomes of 109 Lactococcus species. These newly-mined propeptides were introduced after the N-terminal USP45 secretion signal to characterize and compare their effects on the secretion of Escherichia coli thioredoxin (TRX) and Flavobacterium meningosepticum prolyl endopeptidase (Fm PEP) in Lactococcus lactis NZ9000. All three propeptides, along with the positive control LEISSTCDA, improved volumetric secretion yields by 1.4–2.3-folds. However, enhancement of secretion yield is dependent on protein of interest. For TRX, the optimal combination of USP45 signal peptide and LEISSTCDA produced a 2.3-fold increase in secretion yields. Whilst for Fm PEP, propeptide 1 with USP45 signal peptide improved volumetric secretion yields by 2.2-fold compared to a 1.4-fold increase by LEISSTCDA. Similar trends in Fm PEP activity and protein yield also demonstrated minimal effect of the negative charged propeptides on PEP activity and thus folding.ConclusionsOverall, we have characterized three new propeptides for use in L. lactis secretion optimization. From success of these propeptides for improvement of secretion yields, we anticipate this collection to be valuable to heterologous protein secretion optimisation in lactic acid bacteria. We have also demonstrated for the first time, secretion of Fm PEP in L. lactis for potential use as a therapy agent in celiac disease.

Generation and characterization of a novel candidate gene therapy and vaccination vector based on human species D adenovirus type 56.

The vectorization of rare human adenovirus (HAdV) types will widen our knowledge of this family and their interaction with cells, tissues and organs. In this study we focus on HAdV-56, a member of human Ad species D, and create ease-of-use cloning systems to generate recombinant HAdV-56 vectors carrying foreign genes. We present in vitro transduction profiles for HAdV-56 in direct comparison to the most commonly used HAdV-5-based vector. In vivo characterizations demonstrate that when it is delivered intravenously (i.v.) HAdV-56 mainly targets the spleen and, to a lesser extent, the lungs, whilst largely bypassing liver transduction in mice. HAdV-56 triggered robust inflammatory and cellular immune responses, with higher induction of IFNγ, TNFα, IL5, IL6, IP10, MCP1 and MIG1 compared to HAdV-5 following i.v. administration. We also investigated its potential as a vaccine vector candidate by performing prime immunizations in mice with HAdV-56 encoding luciferase (HAdV-56-Luc). Direct comparisons were made to HAdV-26, a highly potent human vaccine vector currently in phase II clinical trials. HAdV-56-Luc induced luciferase 'antigen'-specific IFNγ-producing cells and anti-HAdV-56 neutralizing antibodies in Balb/c mice, demonstrating a near identical profile to that of HAdV-26. Taken together, the data presented provides further insight into human Ad receptor/co-receptor usage, and the first report on HAdV-56 vectors and their potential for gene therapy and vaccine applications.

Insights Into the Ecology of Grapevine red blotch virus in a Diseased Vineyard.

Limited information is available on the spread of Grapevine red blotch virus (GRBV, genus Grablovirus, family Geminiviridae) in vineyards. To investigate ecological aspects of red blotch disease spread, sticky cards to catch flying insects were placed in 2015 (April to November) and 2016 (March to November) in a vineyard study site in California where disease incidence increased by nearly 20% between 2014 and 2016. Subsets of insect species or taxa were removed from sticky card traps and individual specimens were tested for the presence of GRBV by multiplex polymerase chain reaction. GRBV was consistently detected in Spissistilus festinus (Membracidae), Colladonus reductus (Cicadellidae), Osbornellus borealis (Cicadellidae), and a Melanoliarus sp. (Cixiidae). Populations of these four candidate vectors peaked from June to September, with viruliferous S. festinus peaking from late June to early July in both years. An assessment of co-occurrence and covariation between the spatial distribution of GRBV-infected vines and viruliferous insects identified a significant association only with viruliferous S. festinus. These findings revealed the epidemiological relevance of S. festinus as a vector of GRBV in a vineyard ecosystem. Sequencing coat protein and replicase-associated protein gene fragments of GRBV isolates from newly infected vines and viruliferous vector candidates further suggested secondary spread primarily from local sources and occasionally from background sources.

Nonencapsidated 5' Copy-Back Defective Interfering Genomes Produced by Recombinant Measles Viruses Are Recognized by RIG-I and LGP2 but Not MDA5.

Attenuated measles virus (MV) is one of the most effective and safe vaccines available, making it an attractive candidate vector for preventing other infectious diseases. Yet the great capacity of this vaccine still needs to be understood at the molecular level. MV vaccine strains have different type I interferon (IFN)-inducing abilities that partially depend on the presence of 5' copy-back defective interfering genomes (DI-RNAs). DI-RNAs are pathogen-associated molecular patterns recognized by RIG-I-like receptors (RLRs) (RIG-I, MDA5, and LGP2) that activate innate immune signaling and shape the adaptive immune response. In this study, we characterized the DI-RNAs produced by various modified recombinant MVs (rMVs), including vaccine candidates, as well as wild-type MV. All tested rMVs produced 5' copy-back DI-RNAs that were different in length and nucleotide sequence but still respected the so-called "rule of six." We correlated the presence of DI-RNAs with a larger stimulation of the IFN-β pathway and compared their immunostimulatory potentials. Importantly, we revealed that encapsidation of DI-RNA molecules within the MV nucleocapsid abolished their immunoactive properties. Furthermore, we identified specific interactions of DI-RNAs with both RIG-I and LGP2 but not MDA5. Our results suggest that DI-RNAs produced by rMV vaccine candidates may indeed strengthen their efficiency by triggering RLR signaling.IMPORTANCE Having been administered to hundreds of millions of children, the live attenuated measles virus (MV) vaccine is the safest and most widely used human vaccine, providing high protection with long-term memory. Additionally, recombinant MVs carrying heterologous antigens are promising vectors for new vaccines. The great capacity of this vaccine still needs to be elucidated at the molecular level. Here we document that recombinant MVs produce defective interfering genomes that have high immunostimulatory properties via their binding to RIG-I and LGP2 proteins, both of which are cytosolic nonself RNA sensors of innate immunity. Defective interfering genome production during viral replication should be considered of great importance due to the immunostimulatory properties of these genomes as intrinsic adjuvants produced by the vector that increase recognition by the innate immune system.