How Biotechs Are Racing to Develop SARS-CoV-2 Vaccines
This is the final article in a three-part series on the efforts of life science organizations to fight the SARS-CoV 2 pandemic. Read more about the industry’s work in How biotechs are racing to develop COVID-19 tests and How biotechs are racing to develop COVID-19 treatments.
Amidst the relief efforts for the coronavirus pandemic, many actors are working to support an array of needs, from treatments to diagnostics to PPE for health-care workers and more. In the long-term, perhaps the most vital solution to the current global health crisis is a vaccine. Since the emergence and spread of the novel coronavirus, SARS-CoV-2, pharmaceutical companies, research institutions, NGOs, and governmental organizations have been forging connections and rapidly accelerating pathways for discovering and developing vaccines. Traditionally, it can take years to design, develop, approve, and deploy vaccines. But in the fight against the novel coronavirus, companies and health organizations alike are finding unprecedented solutions to shorten timelines – with experts saying potentially 12-18 months – to get a vaccine to the public as quickly as possible.
Governmental and NGO Support of SARS-CoV-2 Vaccine Discovery and Development
Before we discuss biotech and pharmaceutical companies that are making progress on vaccines, let’s first recognize the health organizations that are coordinating, tracking, and in some cases funding, vaccine trials for SARS-CoV-2. The following summarizes the efforts of four organizations: the WHO, BARDA, NIAID/NIH, and CEPI.
The World Health Organization (WHO)
The World Health Organization (WHO) has launched an international vaccine trial, named the Solidarity Vaccine Trial, to coordinate and evaluate the myriad potential SARS-CoV-2 vaccines that are in research and development. The trial will take place at several sites across multiple countries and is designed to accept candidate vaccines as they become available and test these vaccines in parallel, instead of one after the other. What’s more, the WHO aims to “evaluate the risks and benefits” of a given vaccine 3-6 months after the WHO starts testing it due to the adaptive design of the study. There will likely be dozens of companies and institutions that submit vaccines to the Solidarity Vaccine Trial throughout the year, leading to robust testing for an ideal vaccine candidate.
Biomedical Advanced Research and Development Authority (BARDA)
In the US, there are several governmental agencies that are collaborating with the private sector. One such organization is the Biomedical Advanced Research and Development Authority (BARDA) which is a branch of the Health and Human Services (HHS) Office of the Assistant Secretary for Preparedness and Response. BARDA is tasked with responding to chemical, biological, radiological, and nuclear threats, which includes pandemics, and they are funding a laundry list of initiatives from diagnostics to therapeutics as well as vaccines. Their vaccine partnerships include Moderna, Janssen Research & Development, and Sanofi Pasteur.
National Institutes of Allergy and Infectious Diseases (NIAID)
Also in the US, the National Institute of Allergy and Infectious Diseases (NIAID) has been leading several efforts to find solutions for the coronavirus pandemic. One such effort is their partnership with the maker of a vaccine candidate, Moderna Inc. NIAID, which is a department of the National Institutes of Health, is funding the Phase I trial of Moderna’s candidate vaccine mRNA-1273.
Coalition for Epidemic Preparedness Innovations (CEPI)
And finally, Norway based CEPI, or the Coalition for Epidemic Preparedness Innovations, is yet another partner to vaccine hopefuls. CEPI is an international group of collaborators that aids in funding and coordinating the production of vaccines when novel infectious diseases emerge. CEPI is partnering with COVID 0, a project to help fund therapeutics, diagnostics, and vaccines for COVID-19. As an NGO, CEPI has received funding from several countries, including Canada, Belgium, Sweden and Germany, for their efforts in the fight against the novel coronavirus. In turn, CEPI is funding several vaccine searches, including those led by Moderna and NIAID, Inovio and Beijing Advaccine Biotechnology, CureVac, Novavax, as well as the University of Queensland, University of Hong Kong, and the Institut Pasteur and consortium. CEPI is also partnering with GSK to make their adjuvant technology more readily available to vaccine production.
Biotechs with Candidate Vaccines in Phase I
There is a long list of companies working on a SARS-CoV-2 vaccine; the WHO recently published a draft landscape of SARS-CoV-2 vaccine testing with two in clinical trials and nearly 60 in preclinical trials. Since that draft’s publication, another company, Inovio, has moved their candidate into clinical trials, as has Oxford University. Moderna received attention for shipping the first vaccine to clinical trials in February. CanSino Bio received approval for clinical trials in late March. Other companies are releasing aggressive plans to get to the clinic as quickly as possible. Below is an overview of the four vaccines currently in Phase I and a handful that are nearing the Phase I benchmark.
Based in Cambridge, Massachusetts, Moderna focuses on mRNA therapeutics and vaccines. In a press release on February 24, Moderna announced that their vaccine, developed in collaboration with NIAID’s Vaccine Research Center, mRNA-1273 was shipped for the first Phase I trial in the US. This RNA vaccine consists of specially selected mRNA, which codes for the coronavirus S-protein (or spike), that is encapsulated in a lipid nanoparticle. It is designed to trigger the production of proteins in vivo that fight the viral infection. Moderna has been able to develop a vaccine candidate so quickly due to their previous work on the Middle Eastern Respiratory Syndrome virus (MERS-CoV) which is similar to SARS-CoV-2. The trial will last some time, as the patients participating in the study will need to be monitored for a year for signs of common vaccination symptoms, immune response to the vaccine, and other medical conditions. However safety information will be available within weeks. If proven safe, the company can ask for permission from the FDA to move to the next phase of the trial. On April 2, Moderna’s co-founder and chairman, Noubar Afeyan, spoke with news outlets saying that the company could move this vaccine candidate into Phase II trials as early as this spring or early summer.
CanSino Biological Inc. and Beijing Institute of Biotechnology
CanSino Bio, based in China, received regulatory approval to launch a Phase I clinical trial for their candidate vaccine, a non-replicating adenovirus type 5 vector. This Ad5 vaccine is designed with the same platform they used to develop an Ebola vaccine back in 2017. CanSino Bio, along with their partner at Academy of Military Medical Sciences’ Institute of Biotechnology, are testing to see if this non-replicating viral vector vaccine will work against SARS-CoV-2. The Phase I trial will test vaccine dosage as well as efficacy among 108 adult participants from the city of Wuhan. As is the case with vaccine trials, this one will measure whether or not the vaccine triggers an immune response in the participants, and it will not involve exposing them to the novel virus post vaccine administration.
Inovio is based in Plymouth Meeting, Pennsylvania and launched their Phase I trial of the candidate vaccine INO-4800 on April 6. Pre-clinical trials with animal models showed encouraging results, and the Phase I trial, which includes 40 volunteers, expects to have safety and immune response data in the next few months. Similar to Moderna, Inovio has done prior work on a vaccine for the MERS virus, which completed its Phase I study. Inovio’s technology to combat SARS-CoV-2 is two-fold. First, INO-4800 is a DNA vaccine that is carried via a plasmid. DNA vaccines are still a young technology, but Inovio is developing a platform for DNA-based medicines and vaccines to treat a variety of conditions and infectious agents, including HPV, Zika, Ebola, HIV and others. Second, Inovio has developed a proprietary method for vaccine delivery dubbed CELLECTRA. This hand-held device delivers vaccines intramuscularly or intradermally wherein it sends brief electrical pulses that temporarily open pores in the cell that allows CELLECTRA to deliver the plasmids into the cell. As Inovio continues to test INO-4800, the company also plans to produce one million vaccines by the end of 2020 to be ready to distribute.
UK based Oxford University has two programs partnering on their candidate vaccine, ChAdOx1 nCoV-19. Oxford researchers at the Jenner Institute and the Oxford Vaccine Group have begun enrolling what will be up to 510 adult volunteers for the Phase I trial. The team working on this effort had previously designed a promising vaccine for the MERS-CoV, which is a coronavirus similar to the SARS-CoV. Oxford’s current SARS-CoV-2 candidate consists of a non-replicating adenovirus equipped with the genetic information for the S-protein (spike) of the coronavirus. The vaccine intends to prime the body to elicit an immune response if infected with SARS-CoV-2. Like other Phase I studies, this trial will assess the vaccine’s safety and immunogenicity. The group is also scaling up manufacturing of the candidate vaccine so that it is ready to go if it is eventually deemed viable.
Biotech Groups in Preclinical Trials
In addition to the four vaccine candidates discussed above, there are several more in preclinical testing. RNA vaccine hopefuls include candidates from Germany-based Pfizer and their partners at BioNTech, Sanofi Pasteur and their partners at Translate Bio, as well as biotech company CureVac. Johnson & Johnson’s Janssen along with the US department of Health and Human Services are working on an adenovirus vaccine (Ad26) that they have announced will be ready come September 2020 as well as a supply of one billion vaccines for emergency use. Several groups are also nearing Phase I for protein subunit vaccines, including Sanofi Pasteur along with BARDA, Novavax, Generex, and the University of Pittsburgh.
The Road Ahead
While it is true that vaccine testing has historically taken quite some time, and vaccine discovery perhaps even longer, it is also true that today, just a few months after SARS-CoV-2 was declared by the WHO to be a novel virus, there are over 60 candidate vaccines in trials already, 4 of which have advanced to human testing. What’s more, many of the organizations developing and testing candidate vaccines are approaching the steps of the process in parallel, rather than in sequence, so that times to milestone are almost happening in-concert. Perhaps the most remarkable factor in the global search for a SARS-CoV-2 vaccine is the sheer extent of the collaboration we’re seeing across governmental bodies, NGOs, industry, and academia. When it comes to equipping the world with solutions to coronavirus, it is true we still have a lengthy road ahead of us. But by leveraging the full scientific potential of organizations around the world, we are well equipped to walk it.