Characterization of the innate stimulatory capacity of plant-derived virus-like particles bearing influenza hemagglutinin

Won, So-Yoon; Hunt, Kristin; Guak, Hannah; Hasaj, Benedeta; Charland, Nathalie; Landry, Nathalie; Ward, Brian J.; Krawczyk, Connie M.

doi:10.1016/j.vaccine.2018.10.099

Cited by 15 publications

(11 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have previously shown that plant-derived VLPs rapidly interact with human immune cells including B cells, monocytes, and dendritic cells 10,12,18 and that early interactions with human MDMs (i.e., binding, internalization, entry into endosomes and fusion with endosomal membranes) are similar to what happens with wild-type influenza virions. 13 The efficiency of the VLP–MDM interactions may largely be attributable to the particulate form of the VLPs bearing 30–50 HA trimers that stimulate rapid binding and internalization.…”

Section: Discussionmentioning

confidence: 99%

“…The potential for VLP-based vaccines to induce CD8 + T cells has been demonstrated in mice 18 and studies are on-going to determine whether or not similar responses can be elicited in humans. Although conserved T cell epitopes from influenza core proteins have attracted the most attention to date, 3,70 several human CD8 + epitopes have been identified in the HA proteins of both seasonal and avian influenza strains 76,77 and our data suggest that many more may exist.…”

Section: Discussionmentioning

confidence: 99%

“…14,15,17 Simultaneous administration of a plant-derived H1-VLP vaccine with ovalbumin (OVA) was recently shown to elicit an OVA-specific CD8 + T cell response in C57BL/6 mice. 18 The subcellular mechanisms that account for the unusual immunogenicity of the plant-derived VLP-based vaccines are not yet well understood.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Plant-derived virus-like particle vaccines drive cross-presentation of influenza A hemagglutinin peptides by human monocyte-derived macrophages

et al. 2019

Self Cite

View full text Add to dashboard Cite

A growing body of evidence supports the importance of T cell responses to protect against severe influenza, promote viral clearance, and ensure long-term immunity. Plant-derived virus-like particle (VLP) vaccines bearing influenza hemagglutinin (HA) have been shown to elicit strong humoral and CD4 + T cell responses in both pre-clinical and clinical studies. To better understand the immunogenicity of these vaccines, we tracked the intracellular fate of a model HA (A/California/07/2009 H1N1) in human monocyte-derived macrophages (MDMs) following delivery either as VLPs (H1-VLP) or in soluble form. Compared to exposure to soluble HA, pulsing with VLPs resulted in ~3-fold greater intracellular accumulation of HA at 15 min that was driven by clathrin-mediated and clathrin-independent endocytosis as well as macropinocytosis/phagocytosis. At 45 min, soluble HA had largely disappeared suggesting its handling primarily by high-degradative endosomal pathways. Although the overall fluorescence intensity/cell had declined 25% at 45 min after H1-VLP exposure, the endosomal distribution pattern and degree of aggregation suggested that HA delivered by VLP had entered both high-degradative late and low-degradative static early and/or recycling endosomal pathways. At 45 min in the cells pulsed with VLPs, HA was strongly co-localized with Rab5, Rab7, Rab11, MHC II, and MHC I. High-resolution tandem mass spectrometry identified 115 HA-derived peptides associated with MHC I in the H1-VLP-treated MDMs. These data suggest that HA delivery to antigen-presenting cells on plant-derived VLPs facilitates antigen uptake, endosomal processing, and cross-presentation. These observations may help to explain the broad and cross-reactive immune responses generated by these vaccines.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Plant-derived virus-like particle vaccines drive cross-presentation of influenza A hemagglutinin peptides by human monocyte-derived macrophages

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…Lymphocytes from mice immunized with plant-made VLPs secreted higher concentrations of pro-inflammatory cytokines (including IL-12, IL-6, and TNF-α) upon antigenic stimulation. [49] HA from A/California/7/2009 or A/Indonesia/5/05 strains. In vitro assays were performed using mouse dendritic cells.…”

Section: Vlps Produced and Immunization Approach Findings Referencementioning

confidence: 99%

What Does Plant-Based Vaccine Technology Offer to the Fight against COVID-19?

et al. 2020

View full text Add to dashboard Cite

The emergence of new pathogenic viral strains is a constant threat to global health, with the new coronavirus strain COVID-19 as the latest example. COVID-19, caused by the SARS-CoV-2 virus has quickly spread around the globe. This pandemic demands rapid development of drugs and vaccines. Plant-based vaccines are a technology with proven viability, which have led to promising results for candidates evaluated at the clinical level, meaning this technology could contribute towards the fight against COVID-19. Herein, a perspective in how plant-based vaccines can be developed against COVID-19 is presented. Injectable vaccines could be generated by using transient expression systems, which offer the highest protein yields and are already adopted at the industrial level to produce VLPs-vaccines and other biopharmaceuticals under GMPC-processes. Stably-transformed plants are another option, but this approach requires more time for the development of antigen-producing lines. Nonetheless, this approach offers the possibility of developing oral vaccines in which the plant cell could act as the antigen delivery agent. Therefore, this is the most attractive approach in terms of cost, easy delivery, and mucosal immunity induction. The development of multiepitope, rationally-designed vaccines is also discussed regarding the experience gained in expression of chimeric immunogenic proteins in plant systems.

show abstract

“…These HA-only VLPs were demonstrated to have potent immunogenicity [ 95 , 96 ]. Won et al, 2018 [ 97 ] showed that these HA VLPs could elicit rapid pro-inflammatory cytokine responses from human and mouse dendritic cells in vitro as well as stimulate T cells to produce antigen-specific responses. Upon immunization of mouse models, there was an accumulation of B- and T-cells as well as DCs in draining lymph nodes.…”

Section: Influenza Virus Vaccinesmentioning

confidence: 99%

Combating Human Viral Diseases: Will Plant-Based Vaccines Be the Answer?

et al. 2021

View full text Add to dashboard Cite

Molecular pharming or the technology of application of plants and plant cell culture to manufacture high-value recombinant proteins has progressed a long way over the last three decades. Whether generated in transgenic plants by stable expression or in plant virus-based transient expression systems, biopharmaceuticals have been produced to combat several human viral diseases that have impacted the world in pandemic proportions. Plants have been variously employed in expressing a host of viral antigens as well as monoclonal antibodies. Many of these biopharmaceuticals have shown great promise in animal models and several of them have performed successfully in clinical trials. The current review elaborates the strategies and successes achieved in generating plant-derived vaccines to target several virus-induced health concerns including highly communicable infectious viral diseases. Importantly, plant-made biopharmaceuticals against hepatitis B virus (HBV), hepatitis C virus (HCV), the cancer-causing virus human papillomavirus (HPV), human immunodeficiency virus (HIV), influenza virus, zika virus, and the emerging respiratory virus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have been discussed. The use of plant virus-derived nanoparticles (VNPs) and virus-like particles (VLPs) in generating plant-based vaccines are extensively addressed. The review closes with a critical look at the caveats of plant-based molecular pharming and future prospects towards further advancements in this technology. The use of biopharmed viral vaccines in human medicine and as part of emergency response vaccines and therapeutics in humans looks promising for the near future.

show abstract

Characterization of the innate stimulatory capacity of plant-derived virus-like particles bearing influenza hemagglutinin

Cited by 15 publications

References 35 publications

Plant-derived virus-like particle vaccines drive cross-presentation of influenza A hemagglutinin peptides by human monocyte-derived macrophages

Plant-derived virus-like particle vaccines drive cross-presentation of influenza A hemagglutinin peptides by human monocyte-derived macrophages

What Does Plant-Based Vaccine Technology Offer to the Fight against COVID-19?

Combating Human Viral Diseases: Will Plant-Based Vaccines Be the Answer?

Contact Info

Product

Resources

About