A plant-produced SARS-CoV-2 spike protein elicits heterologous immunity in hamsters.

Molecular farming of vaccines has been heralded as a cheap, safe and scalable production platform. In reality, however, differences in the plant biosynthetic machinery, compared to mammalian cells, can complicate the production of viral glycoproteins. Remodelling the secretory pathway presents an opportunity to support key post-translational modifications, and to tailor aspects of glycosylation and glycosylation-directed folding.

Optimal size of DNA encapsidated by plant produced human papillomavirus pseudovirions.

Human papillomaviruses (HPVs) are known to be the cause of anogenital and oropharyngeal cancers as well as genital and common warts. HPV pseudovirions (PsVs) are synthetic viral particles that are made up of the L1 major and L2 minor HPV capsid proteins and up to 8 Kb of encapsidated pseudogenome dsDNA. HPV PsVs are used to test novel neutralising antibodies elicited by vaccines, for studying the virus life cycle, and potentially for the delivery of therapeutic DNA vaccines.

Recovery from Beak and Feather Disease Virus Infection in a Cape Parrot (Poicephalus robustus) Population in South Africa.

Psittacine beak and feather disease (PBFD) is one of the most important viral diseases affecting parrot species worldwide. Outbreaks of PBFD have been reported in wild endemic and endangered South African Cape Parrots (Poicephalus robustus), most recently in 2008. A previous study of wild Cape Parrots in the Eastern Cape region of South Africa in 2010-11 found 34/49 birds positive for beak and feather disease virus (BFDV), the causative agent of PBFD, showing that the outbreak was still ongoing.

Augmenting glycosylation-directed folding pathways enhances the fidelity of HIV Env immunogen production in plants.

Heterologous glycoprotein production relies on host glycosylation-dependent folding. When the biosynthetic machinery differs from the usual expression host, there is scope to remodel the assembly pathway to enhance glycoprotein production. Here we explore the integration of chaperone coexpression with glyco-engineering to improve the production of a model HIV-1 envelope antigen.

Plant expression systems as an economical alternative for the production of iELISA coating antigen AHSV VP7.

African horse sickness (AHS) is a debilitating and highly infectious arthropod-borne disease affecting all species of Equidae. The causative agent of AHS is the non-enveloped dsRNA African horse sickness virus (AHSV), belonging in the genus Orbivirus, family Reoviridae. The identification and surveillance of AHSV by simple and reliable diagnostic tools is essential for managing AHS outbreaks.

Eroding norms over release of self-spreading viruses.

Risky research on lab-modified self-spreading viruses has yet to present credible paths to upsides.

A Plant-Produced Virus-Like Particle Displaying Envelope Protein Domain III Elicits an Immune Response Against West Nile Virus in Mice.

West Nile virus (WNV) is a globally disseminated that is associated with encephalitis outbreaks in humans and horses. The continuous global outbreaks of West Nile disease in the bird, human, and horse populations, with no preventative measures for humans, pose a major public health threat. The development of a vaccine that contributes to the "One Health" Initiative could be the answer to prevent the spread of the virus and control human and animal disease.

Humoral and cell-mediated immune responses to plant-produced African horse sickness virus VP7 quasi-crystals.

African horse sickness (AHS) is a devastating viral disease affecting equines and has resulted in many disastrous epizootics. To date, no successful therapeutic treatment exists for AHS, and commercially used live-attenuated vaccines have various undesirable side effects. Previous studies have shown that mice inoculated with insoluble African horse sickness virus (AHSV) VP7 crystals are protected from live challenge with a lethal dose of AHSV.

A Roadmap for the Molecular Farming of Viral Glycoprotein Vaccines: Engineering Glycosylation and Glycosylation-Directed Folding.

Immunization with recombinant glycoprotein-based vaccines is a promising approach to induce protective immunity against viruses. However, the complex biosynthetic maturation requirements of these glycoproteins typically necessitate their production in mammalian cells to support their folding and post-translational modification. Despite these clear advantages, the incumbent costs and infrastructure requirements with this approach can be prohibitive in developing countries, and the production scales and timelines may prove limiting when applying these production systems to the control of pandemic viral outbreaks.

Immunogenicity of Plant-Produced Human Papillomavirus (HPV) Virus-Like Particles (VLPs).

Cervical cancer is ranked fourth among the top cancers in women and is the second most common cancer in low- and middle-income regions, with ~570,000 new cases reported in 2018, which attributed to 84% of worldwide cervical cancer cases. Three commercially available prophylactic Human papillomavirus (HPV) vaccines are effective at preventing HPV infections. However, these vaccines are expensive due to their complex production systems, therefore limiting their use in developing countries.

Extended Set of GoldenBraid Compatible Vectors for Fast Assembly of Multigenic Constructs and Their Use to Create Geminiviral Expression Vectors.

Methods for simple and fast assembly of exchangeable standard DNA parts using Type II S restriction enzymes are becoming more and more popular in plant synthetic and molecular biology. These methods enable routine construction of large and complex multigene DNA structures. Two available frameworks emphasize either high cloning capacity (Modular Cloning, MoClo) or simplicity (GoldenBraid, GB).

Prospects for SARS-CoV-2 diagnostics, therapeutics and vaccines in Africa.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a global pandemic, prompting unprecedented efforts to contain the virus. Many developed countries have implemented widespread testing and have rapidly mobilized research programmes to develop vaccines and therapeutics. However, these approaches may be impractical in Africa, where the infrastructure for testing is poorly developed and owing to the limited manufacturing capacity to produce pharmaceuticals.

Engineering the Plant Secretory Pathway for the Production of Next-Generation Pharmaceuticals.

Production of biologics in plants, or plant molecular pharming, is a promising protein expression technology that is receiving increasing attention from the pharmaceutical industry. Previously, low expression yields of recombinant proteins and the realization that certain post-translational modifications (PTMs) may not occur optimally limited the widespread acceptance of the technology. However, molecular engineering of the plant secretory pathway is now enabling the production of increasingly complex biomolecules using tailored protein-specific approaches to ensure their maturation.

Transient protein expression in tobacco BY-2 plant cell packs using single and multi-cassette replicating vectors.

This is the first evidence that replicating vectors can be successfully used for transient protein expression in BY-2 plant cell packs. Transient recombinant protein expression in plants and recently also plant cell cultures are of increasing interest due to the speed, safety and scalability of the process. Currently, studies are focussing on the design of plant virus-derived vectors to achieve higher amounts of transiently expressed proteins in these systems.

Characterization and Immunogenicity of HIV Envelope gp140 Zera Tagged Antigens.

HIV-1 envelope glycoprotein (Env) remains the most relevant target for the elicitation of functional antibodies to HIV by vaccination. However, soluble Env antigens often do not elicit the desired immune responses. Delivering subunit antigens on particulate nanoparticles is an established approach to improve their immunogenicity.

Co-expression of human calreticulin significantly improves the production of HIV gp140 and other viral glycoproteins in plants.

Plant molecular farming (PMF) is rapidly gaining traction as a viable alternative to the currently accepted paradigm of producing biologics. While the platform is potentially cheaper and more scalable than conventional manufacturing systems, expression yields and appropriate post-translational modifications along the plant secretory pathway remain a challenge for certain proteins. Viral fusion glycoproteins in particular are often expressed at low yields in plants and, in some cases, may not be appropriately processed.

Symptom evolution following the emergence of maize streak virus.

For pathogens infecting single host species evolutionary trade-offs have previously been demonstrated between pathogen-induced mortality rates and transmission rates. It remains unclear, however, how such trade-offs impact sub-lethal pathogen-inflicted damage, and whether these trade-offs even occur in broad host-range pathogens. Here, we examine changes over the past 110 years in symptoms induced in maize by the broad host-range pathogen, maize streak virus (MSV).

Production and Immunogenicity of Soluble Plant-Produced HIV-1 Subtype C Envelope gp140 Immunogens.

The development of effective vaccines is urgently needed to curb the spread of human immunodeficiency virus type 1 (HIV-1). A major focal point of current HIV vaccine research is the production of soluble envelope (Env) glycoproteins which reproduce the structure of the native gp160 trimer. These antigens are produced in mammalian cells, which requires a sophisticated infrastructure for manufacture that is mostly absent in developing countries.