Vaccine trials across the globe
As soon as the news of the novel coronavirus began filtering into the scientific community, academics and companies alike began the race to develop a vaccine against SARS-CoV-2, the virus that causes COVID-19.
A myriad of phase I clinical trials, which are primarily focused on ensuring the safety of the proposed vaccines, have sprung up across the globe[1-7]. Each employs a slightly different strategy. As results from these phase I clinical trials are released, scientists will synthesize this information and pursue vaccine candidates that show the most promise for being both safe and efficacious.
Below is a summary of a selection of actively recruiting and ongoing clinical trials across the globe.
The vaccine trials in the United States have focused on nucleic acid vaccines[1-3]. These vaccines are composed of either DNA or nucleoside modified mRNA that encodes for a protein of interest. In the context of SARS-CoV-2, injection of the nucleic acid vaccine will cause cells to produce a protein; this protein production will act as a jump start to the body’s immune system. The immune system will then produce antibodies, which are key proteins that help guide the clearance of pathogens.
Photo: Vaccine bottle and syringe.
There are three main clinical trials ongoing in the US. Two are mRNA based vaccines; one produced by Moderna in partnership with the National Institute of Allergy and Infectious Disease and one produced by Pfizer and BioNtech (a German company, but the trial is being conducted in the United States). The Moderna and NIAID vaccine encodes for the SARS-CoV-2 spike protein, a protein that is crucial for viral entry into host cells[1,8]. The Pfizer and BioNtech vaccine candidate has several different formulations that are being tested, two of which encode for the spike protein, and two that only encode the portion of the spike protein that specifically interacts with host cells (receptor binding domain).
On the DNA vaccine side, Inovio Pharmaceuticals has produced a vaccine candidate that also encodes for the spike protein. For more information on this vaccine, as well as the two mRNA vaccines, click here.
China has also begun clinical trials on several vaccine candidates. In contrast to the United States, they are focusing their efforts on inactivated vaccine and adenoviral-based vector vaccines[4-6], though this is by no means an exhaustive list of the trials underway.
Inactivated vaccines are typically made by killing a pathogenic virus or bacterium with heat or chemicals. The inactivated cell can then be used as the vaccine, or components can be purified further. Using an entire cell can be advantageous in vaccine development because a cell provides multiple different antigens, proteins that can help elicit an immune response, for the body to react to. Many important vaccines in the United States, such as the polio and hepatitis A, are inactivated whole cell vaccines.
An inactivated vaccine was manufactured by Sinovac Research and Development Co., Ltd. Virus was isolated from a COVID-19 patient and then treated with beta-propiolactone, a commonly used chemical inactivating agent[10,11]. There are two vaccine trials in China that both address the safety and efficacy of Sinovac’s inactivated vaccine. The first trial focuses on 18-59 year olds. This month, a second clinical trial was begun for individuals over 60 years of age. Preliminary results for these trials are expected in August and July, respectively.
Using a different approach, Beijing Institute of Biotechnology and CanSino Biologics Inc have developed an adenoviral based vaccine as their vaccine candidate. Adenovirus is notable for producing robust immune responses in both the innate and adaptive arms of the immune system, which together can provide a stronger immune response than either of these arms alone. This vaccine candidate has been engineered to become replication deficient, removing its ability to lyse host cells, and it displays the SARS-CoV-2 spike protein as its antigen. Preliminary results from this study have been recently published. The vaccine trial was divided into three dose groups; mild adverse reactions such as fever and fatigue were commonly reported (around 40-50% in each dose group). However, these adverse events are not classified as severe, and early evidence indicates that the vaccine was able to induce neutralizing antibodies in many of the subjects, in a dose dependent manner. Follow up information on the study will be obtained over the next 6 months.
Novavax is another company that has manufactured a prospective vaccine; their candidate is a nanoparticle vaccine[7,14]. Though the company is based in the United States, the clinical trial is taking place in Australia.
Nanoparticles are self assembling structures that, in the context of vaccines, are able to help amplify the immune response against the desired antigen. By manipulating the properties of different components in the nanoparticle, it is possible to direct delivery of the nanoparticle to particular organs and tailor the immune response. In addition, nanoparticle-based vaccines have generated interest in that they are often considered to be safer alternatives than some types of cell-based vaccines.
The vaccine candidate being tested in Australia’s clinical trial is a nanoparticle that presumably displays a recombinant version of the SARS-CoV-2 spike protein, but the particulars have been kept largely under wraps as the technology used to develop it is proprietary. The trial will test the safety and efficacy of the nanoparticle vaccine as is, as well as in combination with Novavax’s MATRIX-M™ adjuvant. An adjuvant is often delivered in a vaccine to help boost immune responses and enhance antibody production.
- Clinical trial US “Safety and Immunogenicity Study of 2019-nCoV Vaccine (mRNA-1273) for Prophylaxis of SARS-CoV-2 Infection (COVID-19)”
- Clinical trial US “Safety, Tolerability and Immunogenicity of INO-4800 for COVID-19 in Healthy Volunteers”
- Clinical trial US “Study to Describe the Safety, Tolerability, Immunogenicity, and Potential Efficacy of RNA Vaccine Candidates Against COVID-19 in Healthy Adults”
- Clinical trial China “Safety and Immunogenicity Study of Inactivated Vaccine for Prophylaxis of SARS CoV-2 Infection (COVID-19)”
- Clinical trial China “Safety and Immunogenicity Study of Inactivated Vaccine for Prevention of SARS-CoV-2 Infection(COVID-19)”
- Clinical trial China “Phase I Clinical Trial of a COVID-19 Vaccine in 18-60 Healthy Adults (CTCOVID-19)”
- Clinical trial Australia “Evaluation of the Safety and Immunogenicity of a SARS-CoV-2 rS (COVID-19) Nanoparticle Vaccine With/Without Matrix-M Adjuvant”
- Manhas et al. “Covid-19 Pandemic and Current Medical Interventions” Archives of Medical Research (2020)
- Gao et al. “Development of an inactivated vaccine candidate for SARS-CoV-2” Science (2020)
- Bonnafous et al. “Treatment of influenza virus with Beta-propiolactone alters viral membrane fusion” Biochimica et Biophysica Acta (BBA) – Biomembranes (2014)
- Tatsis et al.”Adenoviruses as vaccine vectors” Molecular Therapy (2016)
- Zhu et al. “Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial” The Lancet (2020)
- “Novavax Identifies Coronavirus Vaccine Candidate; Accelerates Initiation of First-in-Human Trial to Mid-May” Novavax press release
- Pati et al. “Nanoparticle Vaccines Against Infectious Disease” Frontiers in Immunology (2018)
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