Vaccine nanoparticles displaying recombinant Ebola virus glycoprotein for induction of potent antibody and polyfunctional T cell responses

Bazzill, Joseph; Stronsky, Sabrina M.; Kalinyak, Laura; Ochyl, Lukasz J.; Steffens, Jesse; Tongeren, Sean A. Van; Cooper, Christopher L.; Moon, James J.

doi:10.1016/j.nano.2018.11.005

Cited by 20 publications

(21 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Notably, previous studies have shown that subunit vaccines based on eGP were able to protect vaccinated mice against lethal EBOV challenge [29,30]. Bazzill, J. D. et al [31] proved that a recombinant EBOV antigen (eGP) incorporated into lipid-based nanoparticles could efficiently generate germinal center B cells and polyfunctional T cells while eliciting robust neutralizing antibody responses. Furthermore, the absence of the signal sequence and transmembrane domain facilitated protein expression [10].…”

Section: Discussionmentioning

confidence: 99%

A Novel Bacterium-Like Particle-Based Vaccine Displaying the SUDV Glycoprotein Induces Potent Humoral and Cellular Immune Responses in Mice

Jiao

Jin

et al. 2019

Viruses

View full text Add to dashboard Cite

Sudan virus (SUDV) causes severe lethal hemorrhagic fever in humans and nonhuman primates. The most effective and economical way to protect against Sudan ebolavirus disease is prophylactic vaccination. However, there are no licensed vaccines to prevent SUDV infections. In this study, a bacterium-like particle (BLP)-based vaccine displaying the extracellular domain of the SUDV glycoprotein (eGP) was developed based on a gram-positive enhancer matrix-protein anchor (GEM-PA) surface display system. Expression of the recombinant GEM-displayed eGP (eGP-PA-GEM) was verified by Western blotting and immunofluorescence assays. The SUDV BLPs (SBLPs), which were mixed with Montanide ISA 201VG plus Poly (I:C) combined adjuvant, could induce high SUDV GP-specific IgG titers of up to 1:40,960 and robust virus-neutralizing antibody titers reached 1:460. The SBLP also elicited T-helper 1 (Th1) and T-helper 2 (Th2) cell-mediated immunity. These data indicate that the SBLP subunit vaccine has the potential to be developed into a promising candidate vaccine against SUDV infections. Viruses 2019, 11, 1149 2 of 15 and receiving unprecedented attention worldwide [4]. Unfortunately, an EVD outbreak occurred again in 2018 in eastern Democratic Republic of Congo and, as of August 2019, a total of 2997 EVD cases had been reported, including 2892 confirmed cases with 1998 deaths (overall case fatality rate of 67%) [5]. Since the first outbreak was reported in 1976, five different species of ebolaviruses, including Ebola virus (EBOV), Sudan virus (SUDV), Reston virus (RESTV), Bundibugyo virus (BDBV), and Taï Forest virus (TAFV,) have been identified and their genomic sequences differ by~35-45% [2]. Excluding EBOV, SUDV has the highest mortality and outbreak rates among the species of ebolaviruses. SUDV has emerged at least six times with average mortality rates of up to 53.76% [6,7]. Multiple vaccines and monoclonal antibodies against EBOV have been developed, but very few of them can effectively prevent and control SUDV infection [8]. Therefore, there is an urgent need to develop a safe and efficacious vaccine against SUDV.The EBOV genome encodes nine structural proteins, including the surface envelope glycoprotein (GP) as the only membrane protein [9]. The mature GP protein forms homotrimers on the surface of infected cells and virions, which is crucial for receptor binding, viral entry, and host immunity induction, making GP an ideal vaccine target [10]. A number of candidate vaccines for EBOV have demonstrated protection against lethal EBOV challenge in animal models and progressed to clinical trials, and most of these vaccines, including DNA vaccines [11], vaccines based on viral vectors, such as recombinant adenovirus [12] and vesicular stomatitis virus (VSV) [13], and protein-based vaccines, such as virus-like particles (VLPs) [14], have been based on GP. Most notably, a number of the candidate vaccines currently under clinical phase evaluation are viral vector-based vaccines [15,16]. While recombinant vesicular stomatitis virus (rVS...

show abstract

Section: Discussionmentioning

confidence: 99%

A Novel Bacterium-Like Particle-Based Vaccine Displaying the SUDV Glycoprotein Induces Potent Humoral and Cellular Immune Responses in Mice

Jiao

Jin

et al. 2019

Viruses

View full text Add to dashboard Cite

show abstract

“…This role makes antibodies targeting this antigen very effective at preventing infection. Bazzill et al developed lipid‐based NPs called interbilayer crosslinked multilamellar vesicles (ICMVs) . These ICMVs were engineered to display EBOV GP in a controlled orientation ( Figure a).…”

Section: Biomaterials Provide Control Over the Molecular Properties Omentioning

confidence: 99%

Section: Biomaterials Provide Control Over the Molecular Properties Omentioning

confidence: 99%

“…b) These capsids can be loaded onto ICMVs in a random fashion without NTA‐functionalized lipids or in a controlled fashion by using NTA‐functionalized lipids at the base of the construct. Reproduced with permission . Copyright 2019, Elsevier.…”

Section: Biomaterials Provide Control Over the Molecular Properties Omentioning

confidence: 99%

Section: Biomaterials Provide Control Over the Molecular Properties Omentioning

confidence: 99%

See 2 more Smart Citations

Biomaterials as Tools to Decode Immunity

Eppler¹,

Jewell

2019

Advanced Materials

View full text Add to dashboard Cite

The immune system has remarkable capabilities to combat disease with exquisite selectivity. This feature has enabled vaccines that provide protection for decades and, more recently, advances in immunotherapies that can cure some cancers. Greater control over how immune signals are presented, delivered, and processed will help drive even more powerful options that are also safe. Such advances will be underpinned by new tools that probe how immune signals are integrated by immune cells and tissues. Biomaterials are valuable resources to support this goal, offering robust, tunable properties. The growing role of biomaterials as tools to dissect immune function in fundamental and translational contexts is highlighted. These technologies can serve as tools to understand the immune system across molecular, cellular, and tissue length scales. A common theme is exploiting biomaterial features to rationally direct how specific immune cells or organs encounter a signal. This precision strategy, enabled by distinct material properties, allows isolation of immunological parameters or processes in a way that is challenging with conventional approaches. The utility of these capabilities is demonstrated through examples in vaccines for infectious disease and cancer immunotherapy, as well as settings of immune regulation that include autoimmunity and transplantation.

show abstract

Materials for Immunotherapy

et al. 2019

View full text Add to dashboard Cite

Breakthroughs in materials engineering have accelerated the progress of immunotherapy in preclinical studies. The interplay of chemistry and materials has resulted in improved loading, targeting, and release of immunomodulatory agents. An overview of the materials that are used to enable or improve the success of immunotherapies in preclinical studies is presented, from immunosuppressive to proinflammatory strategies, with particular emphasis on technologies poised for clinical translation. The materials are organized based on their characteristic length scale, whereby the enabling feature of each technology is organized by the structure of that material. For example, the mechanisms by which i) nanoscale materials can improve targeting and infiltration of immunomodulatory payloads into tissues and cells, ii) microscale materials can facilitate cell‐mediated transport and serve as artificial antigen‐presenting cells, and iii) macroscale materials can form the basis of artificial microenvironments to promote cell infiltration and reprogramming are discussed. As a step toward establishing a set of design rules for future immunotherapies, materials that intrinsically activate or suppress the immune system are reviewed. Finally, a brief outlook on the trajectory of these systems and how they may be improved to address unsolved challenges in cancer, infectious diseases, and autoimmunity is presented.

show abstract

Vaccine nanoparticles displaying recombinant Ebola virus glycoprotein for induction of potent antibody and polyfunctional T cell responses

Cited by 20 publications

References 35 publications

A Novel Bacterium-Like Particle-Based Vaccine Displaying the SUDV Glycoprotein Induces Potent Humoral and Cellular Immune Responses in Mice

A Novel Bacterium-Like Particle-Based Vaccine Displaying the SUDV Glycoprotein Induces Potent Humoral and Cellular Immune Responses in Mice

Biomaterials as Tools to Decode Immunity

Materials for Immunotherapy

Contact Info

Product

Resources

About