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Decoding GPΔTM: A Molecular Key to Ebola and Marburg Virus Vaccine Innovation
Published On 03/25/2025 2:22 PM
As the global scientific community races to stay ahead of emerging infectious diseases, filoviruses such as Zaire Ebola virus (EBOV), Marburg virus (MARV), and Sudan virus (SUDV) remain at the forefront of vaccine and therapeutic development. One molecular target stands out across all three: the viral glycoprotein lacking the transmembrane domain, or GPΔTM.
This truncated version of the viral glycoprotein (GP), which omits the hydrophobic transmembrane region, preserves essential structural and antigenic features while allowing for enhanced solubility and expression. It is a powerful tool for structural biology, vaccine design, and immunodiagnostics.
Zaire Ebola Virus GPΔTM: Gateway to Broad Neutralization
Zaire Ebola virus (EBOV) has been the focus of intense scientific attention due to its history of severe and often deadly outbreaks. One of the most extensively studied components of this virus is its glycoprotein, particularly in the form of a recombinant construct lacking the transmembrane domain—GPΔTM. This soluble version retains the native trimeric structure while being easier to express and manipulate in vitro. Studies have shown that EBOV GPΔTM maintains the dynamic, prefusion conformations that are essential for viral entry, making it highly valuable for understanding membrane fusion and viral pathogenesis. For instance, Durham et al. demonstrated that EBOV GPΔTM exhibits conformational flexibility similar to that seen during viral entry, offering key insights into the virus's fusion mechanism.
Structural work has further enhanced our understanding of how antibodies neutralize the virus. Pallesen et al. resolved the complex between GPΔTM and therapeutic monoclonal antibodies, revealing conserved neutralization epitopes—particularly in the glycan cap and base regions—critical for designing both vaccines and therapeutics. In applied immunology, recombinant EBOV GPΔTM has been used as an immunogen in vaccine studies, showing robust immune stimulation and protective efficacy in preclinical models. For example, Wu et al. demonstrated that an adenoviral vaccine expressing EBOV GPΔTM conferred protection in guinea pigs and nonhuman primates.
Moreover, the utility of GPΔTM extends beyond vaccines into therapeutic antibody screening. Li et al. reported that monoclonal antibodies targeting EBOV GPΔTM conferred complete protection in a hamster model of infection, underscoring the construct’s reliability as a surrogate antigen for in vivo challenge studies. Collectively, EBOV GPΔTM stands as a gold-standard tool for structural biology, immunogenicity profiling, and antibody discovery within the field of Ebola virus research.
Marburg Virus GPΔTM: A Vaccine Antigen on the Rise
Marburg virus (MARV), a filovirus closely related to Ebola virus, has historically received less attention but is no less dangerous—causing hemorrhagic fevers with mortality rates approaching those of EBOV. Like its counterpart, MARV relies on a surface glycoprotein (GP) to mediate host cell entry, and research has increasingly focused on GPΔTM, the transmembrane-deleted version, for its utility in vaccine development and immunological assays. One pivotal study by Janus et al. demonstrated that multivalent immunization using MARV GPΔTM induced a robust and broad-spectrum antibody response in macaques, suggesting the antigen’s strong immunogenicity in a primate model.
Earlier foundational research by Hevey et al. validated the feasibility of producing MARV GPΔTM in insect cell expression systems. Their work showed that even without the full membrane-anchored structure, the GPΔTM retained immunogenic epitopes and was capable of eliciting protective immunity in animal models. This finding helped establish GPΔTM as a viable vaccine component. Expanding on this, Marzi et al. explored the immunological mechanisms behind GPΔTM-based vaccines and found that protection induced by rVSV-MARV vectors expressing GPΔTM required both T and B cell activation, underscoring the construct’s ability to engage both arms of the adaptive immune system.
In addition to traditional mammalian and insect systems, the expression of MARV GPΔTM has also been tested in plant-based platforms such as Nicotiana benthamiana, as reported by Margolin et al. Their work highlights the potential for cost-effective, scalable antigen production, especially important for field-deployable vaccine strategies in low-resource settings. Together, these findings position MARV GPΔTM as a rising and versatile antigen candidate in the filovirus vaccine development pipeline.
Sudan Virus GPΔTM: Toward Cross-Species Protection
Sudan virus (SUDV), though genetically distinct from EBOV, shares critical structural and immunological features that make its glycoprotein a prime target for subunit vaccine development. The use of GPΔTM—lacking the transmembrane region but preserving the immunologically relevant trimeric architecture—has proven instrumental in advancing SUDV vaccine research. In a landmark study, Lee et al. designed a next-generation SUDV GPΔTM construct optimized through structural stabilization, glycan shielding, and nanoparticle display. This engineering approach aimed to improve antigen presentation and durability, ultimately enhancing immune responses.
Complementary research by Wang et al. utilized recombinant vesicular stomatitis virus (rVSV) vectors expressing SUDV GPΔTM to elicit potent neutralizing antibody responses in animal models. These responses were evaluated under acidic pH conditions that mimic the virus’s entry environment within endosomes, lending physiological relevance to the findings. The study demonstrated that SUDV GPΔTM is not only structurally sound but also functionally potent in triggering entry-relevant immunity.
The potential of SUDV GPΔTM extends into multivalent vaccine approaches as well. Liu et al. incorporated SUDV GPΔTM into a broad-spectrum monoclonal antibody cocktail that showed efficacy across multiple ebolavirus species. This underscores the potential of GPΔTM constructs to contribute to cross-species protection—an important goal in preparing for unpredictable future outbreaks. Additionally, Holtsberg et al. demonstrated that SUDV GPΔTM expressed in insect cells can serve as a platform for monoclonal antibody development, broadening its utility beyond vaccines to include therapeutic antibody discovery. Collectively, these studies make a strong case for the critical role of SUDV GPΔTM in the next wave of universal filovirus countermeasures.
Why GPΔTM Matters
Across all three viruses, GPΔTM plays a central role in understanding viral entry, guiding antibody discovery, and engineering next-generation vaccines. By removing the transmembrane domain, researchers can generate stable, trimeric GP forms that mimic the native viral surface without complications in membrane anchoring—perfect for in vitro and in vivo applications.
Whether it’s Zaire, Marburg, or Sudan virus, GPΔTM is not just a fragment—it’s the key to unlocking protective immunity.
The Next
As filoviruses continue to pose significant global health threats, innovative vaccine development and antibody discovery depend increasingly on recombinant antigens that closely mimic native viral structures. At the center of this innovation is GPΔTM, a recombinant glycoprotein variant lacking the transmembrane domain, renowned for its structural integrity, immunogenic potential, and utility in preclinical research.
IBT Bioservices has become a leading supplier of recombinant GPΔTM antigens, enabling critical advancements in preclinical development, serological assays, and structure-guided vaccine design. Discover our complete portfolio of GPΔTM recombinant antigens here:
Explore GPΔTM Products
References
Durham ND, et al. (2020). Real-time analysis of individual Ebola virus glycoproteins reveals pre-fusion, entry-relevant conformational dynamics. Viruses. PDF
Pallesen J, et al. (2016). Structures of Ebola virus GP and sGP in complex with therapeutic antibodies. Nature Microbiology. PDF
Wu S, et al. (2016). An adenovirus vaccine expressing Ebola virus variant Makona glycoprotein is efficacious in guinea pigs and nonhuman primates. JID Supplement. PDF
Li W, et al. (2024). Fully human monoclonal antibodies against Ebola virus possess complete protection in a hamster model. Emerging Microbes & Infections. PDF
Janus BM, et al. (2024). Macaque antibodies targeting Marburg virus glycoprotein induced by multivalent immunization. Journal of Virology. PDF
Hevey M, et al. (2001). Marburg virus vaccines: comparing classical and new approaches. Vaccine
Marzi A, et al. (2018). Protection against Marburg virus using a recombinant VSV-vaccine depends on T and B cell activation. Frontiers in Immunology. PDF
Margolin E, et al. (2021). Site-specific glycosylation of recombinant viral glycoproteins produced in Nicotiana benthamiana. Frontiers in Plant Science. PDF
Lee YZ, et al. (2025). Rational design of next-generation filovirus vaccines with glycoprotein stabilization, nanoparticle display, and glycan modification. bioRxiv. PDF
Wang Y, et al. (2021). Prominent neutralizing antibody response targeting the ebolavirus glycoprotein subunit interface. Journal of Virology. PDF
Liu G, et al. (2023). A pan-Ebolavirus monoclonal antibody cocktail provides protection against Ebola and Sudan viruses. Journal of Infectious Diseases Supplement. PDF
Holtsberg FW, et al. (2016). Pan-ebolavirus and pan-filovirus mouse monoclonal antibodies: protection against Ebola and Sudan viruses. Journal of Virology. PDF
Ilinykh PA, et al. (2024). Antibodies targeting the glycan cap of Ebola virus glycoprotein are potent inducers of the complement system. Communications Biology – Nature. PDF
Banadyga L, et al. (2021). Atypical Ebola virus disease in a nonhuman primate following monoclonal antibody treatment is associated with glycoprotein mutations within the fusion loop. mBio. PDF
Qiu X, et al. (2016). Two-mAb cocktail protects macaques against the Makona variant of Ebola virus. Science Translational Medicine. PDF
Cagigi A, et al. (2018). Vaccine-mediated induction of an Ebolavirus cross-species antibody binding to conserved epitopes on the glycoprotein heptad repeat 2/membrane-proximal external region. Journal of Infectious Diseases Supplement. PDF
Marzi A, et al. (2022). VSV-based vaccine provides species-specific protection against Sudan virus challenge in macaques. bioRxiv. PDF
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