Vaccines, plasma and stem cells: How industry hopes to take on COVID-19

The biopharma space has stepped up its efforts to both prevent and treat the coronavirus (SARS-CoV-2) that is threatening to bring the world to its knees.

A month is a very long time when it comes to infectious diseases. The first cases and deaths from the novel coronavirus (COVID-19) led to a response to contain the virus, but the difficulties of containment and the nature of international travel means cases and deaths have become global.

The latest statistics place the number of cases at 95,483 and deaths at 3,286 across 84 countries, though by the time you are reading this the number is likely to have skyrocketed.

So as the world tilters on the edge of a pandemic, we take a look at how industry is responding. There is no specific treatment for the virus, nor a vaccine, but a proactive response is seeing the pharma industry throw everything in its arsenal at attempting to stymie this global threat.

Vaccines

First off, vaccines. As the World Health Organization (WHO) states “it can take a number of years for a new vaccine to be developed,” it has not stopped companies and academia stepping up their R&D efforts.

Both Sanofi and J&J have separately teamed up with the US Department of Health and Human Services (HHS) to expediate vaccine development.

Sanofi Pasteur aims to reverse engineer proteins isolated from the virus to produce DNA sequences, which will then be mass produced using Sanofi Pasteur’s baculoviral expression system and formulated into a vaccine that elicits an immune response. Well that is the aim.

Johnson & Johnson’s unit Janssen Pharmaceutical, meanwhile, is reviewing products in development for Middle East Respiratory Syndrome (MERS) or Severe Acute Respiratory Syndrome (SARS), to identify promising candidates for the novel coronavirus, and aims to upscale production and manufacturing capacities, leveraging its AdVac and PER.C6 technologies.

Another ‘Big Vaccine’ company, GlaxoSmithKline, has teamed with Chinese biotech Clover Biopharmaceuticals to help develop a preclinical protein-based vaccine candidate. GSK will provide its pandemic adjuvant system for further evaluation of Clover’s ‘S-Trimer,’ a trimeric SARS-CoV-2 spike (S)-protein subunit vaccine candidate produced using a mammalian cell-culture based expression system.

DNA and RNA vaccines

Inovio Pharmaceuticals has also entered the race, and like GSK has teamed up with a Chinese company. Together with Beijing Advaccine Biotechnology and a grant of up to $9 million from the Coalition for Epidemic Preparedness Innovations (CEPI), Inovio hopes to bring its DNA vaccine candidate INO-4800 rapidly into clinical trials. VGXI – a subsidiary of GeneOne Life Science – has been selected to manufacture the DNA vaccine from its facilities in The Woodlands, Texas.

““The genome sequence for 2019-nCoV was published on January 10, 2020,” a VGXI spokesperson recently told Bioprocess Insider. “This DNA sequence information is used by Inovio and their collaborators at the Wistar Institute to design a synthetic DNA plasmid for manufacturing at VGXI. No viral particles or proteins are involved in the manufacturing process. When delivered as a vaccine, the DNA plasmid can elicit a protective immune response.”

RNA vaccines are also being investigated. Moderna Therapeutics recently shipped the first batch of its investigational messenger RNA vaccine mRNA-1273 to the National Institute of Allergy and Infectious Diseases (NIAID) for use in a Phase I study. The vaccine is designed to ‘train’ the immune system to recognize cells invaded by the coronavirus.

Moderna also received a grant from CEPI, as has CureVac, which is looking to use its mRNA vaccine platform to expedite a candidate into trials. “CureVac’s technology and mRNA platform are especially suitable to rapidly provide a response to a viral outbreak situation like this,” said CureVac CTO Mariola Fotin-Mleczek. “Currently, we are in the process of developing a vaccine that, after successful preclinical tests, could be tested rapidly in humans in a clinical study.”

Poultry vaccine

But industry could be pipped to the clinical trial post by academia, with Israel’s MIGAL Research Institute claiming to be sitting on a human vaccine against COVID-19 as a by-product of a vaccine it has developed against avian coronavirus Infectious Bronchitis Virus (IBV).

“From research conducted at MIGAL, it has been found that the poultry coronavirus has high genetic similarity to the human COVID-19, and that it uses the same infection mechanism, a fact that increases the likelihood of achieving an effective human vaccine in a very short period of time,” the Institute says.

According to MIGAL’s Biotechnology group leader Chen Katz, the vaccine is based on “a new protein expression vector, which forms and secretes a chimeric soluble protein that delivers the viral antigen into mucosal tissues by self-activated endocytosis – a cellular process in which substances are brought into a cell by surrounding the material with cell membrane, forming a vesicle containing the ingested material – causing the body to form antibodies against the virus.”

Non-vaccines

Other pharma companies are looking to treat coronavirus, rather than prevent.

Regeneron has teamed with the HHS to use its VelociSuite technologies to identify and validation and develop preclinical candidates and bring them to development, having followed a similar approach to advance its investigational Ebola treatment REGN-EB3.

The tech platform includes the VelocImmune mouse technology, a genetically modified strain in which genes encoding mouse immune system proteins have been replaced by their human equivalents.

“The life-saving results seen with our investigational Ebola therapy last year underscore the potential impact of Regeneron’s rapid response platform for addressing emerging outbreaks,” said George Yancopoulos, Regeneron CSO. “Our unique suite of technologies expedites and improves the drug discovery and development process at every stage, positioning Regeneron to respond quickly and effectively to new pathogens.”

Meanwhile this week, Takeda announced it is looking to a therapy to target COVID-19 based on polyclonal hyperimmune globulin (H-IG). The candidate, TAK-888, aims to concentrate pathogen-specific antibodies from plasma collected from recovered patients. Initially, due to a lack of current donors, the firm will produce the therapy in a segregated area within its manufacturing facility in Georgia.

The Japan-headquartered firm will also review its current pipeline for any other viable candidates to take on COVID-19.

Such an approach has aided Gilead Science’s efforts. The firm has begun two Phase III clinical studies of its antiviral candidate remdesivir, developed (though never approved) to treat Ebola virus. It has also shown promise against other infectious diseases including Marburg, MERS and SARS.

“This is an experimental medicine that has only been used in a small number of patients with COVID-19 to date, so Gilead does not have an appropriately robust understanding of the effect of this drug to warrant broad use at this time,” Gilead said.

With about 1,000 patients set to be tested with remdesivir, Gilead has turned to a stockpile manufactured in response to Ebola to address present coronavirus needs, and – in anticipation of expanded use – is manufacturing two formulations of remdesivir, in both liquid and freeze-dried forms, while upping capacity and production internally and externally.

Stem cells

According to San Marino’s Bioscience Institute SpA, a regenerative medicine center and stem cell production facility, mesenchymal stem cells could potentially be treatment for the novel coronavirus by “improving lung microenvironment, inhibiting immune system overactivation, promoting tissue repair, protecting lung alveoli epithelial cells, preventing pulmonary fibrosis, and improving lung function.”

The company, citing the Chinese open repository for scientific researchers chinaXiv.org , says at least 14 trials are taking place in China using stem cells to treat coronavirus patients after positive animal testing showed stem cells might be able to repair the severe organ damage caused by the virus.

The firm even reports that “a critically ill 65-year-old Chinese woman infected with SARS-CoV-2, whose conditions significantly improved after the infusion of mesenchymal stem cells.”

If mesenchymal stem cells do prove to be the solution to the potential coronavirus crisis, Bioscience Institute alludes to the advantage that they are obtained from fat cells.

“That means that everyone can utilize his/her cells, eliminating any contamination or rejection risk,” said Giuseppe Mucci, CEO of Bioscience Institute.

“But expanding them to the quantity needed for infusion, that corresponds to at least 1 million cells per kg of weight, takes 2 to 3 weeks. That is why it is useful to cryopreserve a personal reserve of mesenchymal stem cells, that would allow to access an early, more successful, treatment.”