The Most Promising Coronavirus Vaccine Candidates Out There

September 15, 2020

Using materials ranging from weakened cold viruses to fragments of genetic code, scientists around the world are creating dozens of unique vaccine candidates to fight the new coronavirus – and they are being developed at an unprecedented pace.

More than six months after the World Health Organization (WHO) first alerted the world to a mysterious cluster of pneumonia cases in Wuhan, China, 166 vaccine candidates are currently in development to prevent the coronavirus (called COVID-19) that causes the disease, according to WHO data. Most of the vaccine candidates are in the preclinical stage, which means they are still being tested on animals or in the lab, but a few of them have entered human trials.

According to the U.S. Food and Drug Administration (FDA), these clinical trials are divided into three or four phases, with the early stages (Phase 1/2) examining the safety, dosage, possible side effects, and efficacy (how well they work against pathogens) of the vaccine candidates in a small group of people. However, the key to getting the vaccine candidate approved is to show promising results in more advanced Phase 3 trials.

In Phase 3 trials, researchers test the vaccine’s efficacy while monitoring hundreds to thousands of volunteers for adverse reactions. The U.S. Centers for Disease Control and Prevention (CDC) says the FDA will approve the vaccine if the trials show that it is safe and effective and that the vaccine’s benefits outweigh its risks. According to the WHO, five coronavirus vaccine candidates have either started recruiting or are in Phase 3 trials. Here are the most promising of these vaccine candidates.

The vaccine currently called ChAdOx1 nCoV-19, commonly known as the Oxford vaccine, was developed by a collaboration between a British university and the pharmaceutical company AstraZeneca. The vaccine is made from a weakened version of the common cold virus (known as adenovirus) that infects chimpanzees. Researchers have genetically modified the virus so that it can’t replicate in humans and added genes that code for the so-called spiking proteins that coronaviruses use to infect human cells. Theoretically, the vaccine would teach the body to recognize these spikes so that the immune system could wipe them out when a person comes in contact with them.

Researchers previously tested the vaccine on rhesus monkeys and found that it didn’t prevent the monkeys from getting infected when they were intentionally exposed to the coronavirus, but it did prevent them from developing pneumonia, suggesting it was partially protective, according to a study published May 13 in the preprint database BioRxiv.

In April, the researchers began testing the vaccine on people and published early results of their Phase I and still ongoing Phase II trials in the journal The Lancet on July 20. The vaccine did not cause any serious adverse reactions in participants, but did suggest some mild side effects, such as muscle aches and chills. The vaccine stimulates the immune system to produce SARS-CoV-2-specific T cells – a group of white blood cells in the fight against the pathogen – and neutralizing antibodies, or molecules that can lock up the virus and prevent it from infecting cells, according to the report.

The phase 3 trial has already begun in Brazil and will enroll up to 5,000 volunteers. Another phase 3 trial is expected to recruit another 10,500 people in the U.K. and 30,000 in the U.S., according to the Oxford Vaccine Trials page and The New York Times. According to The Guardian, the Oxford team has also expressed interest in conducting challenge studies in humans, meaning they would deliberately infect low-risk volunteers with the virus, either at the same time as the phase 3 trial or after it is completed.

The U.S. Department of Health and Human Services (HHS) announced it will provide up to $1.2 billion to AstraZeneca to speed up the vaccine development process and help the company produce at least 300 million doses of the vaccine – if it proves to be safe and effective – as early as October 2020, according to a statement. According to HHS, this is part of the Trump administration’s “Operation Warp Speed,” which aims to deliver 300 million doses of safe and effective vaccine by January 2021.

Huarui Biotechnology Co.
Another vaccine candidate, called (PiCoVacc), is being developed by Beijing-based Sinovac Biotechnology to protect rhesus monkeys from infection by a novel coronavirus, according to a study published in the July 3 issue of Science. The company has proven the vaccine to be safe and effective in early clinical trials and is currently recruiting 8,870 participants for a Phase 3 clinical trial in Brazil, according to clinicaltrials.gov.

The vaccine consists of an inactivated version of the SARS-CoV-2 virus. According to the U.S. Department of Health and Human Services (HHS), an inactivated vaccine is a dead version of the pathogen that causes the disease (as opposed to a weakened virus that acts as a live vaccine). Inactivated viruses, such as influenza vaccine or hepatitis A vaccine, are typically less protective than live vaccines and may require booster shots over time, according to HHS. In contrast, bull vaccines are weakened forms of live vaccines that produce a lasting immune response, but tend to be riskier for people with weakened immune systems or other health problems, according to HHS.

Sinovac began a Phase 1/2 trial (involving 743 healthy adults) in April in China’s Jiangsu province. They gave the participants two doses of the vaccine, two weeks apart, and reported that the vaccine did not cause any serious adverse events, according to a statement. The study authors also said that more than 90 percent of the participants developed neutralizing antibodies two weeks after receiving the second dose of vaccine. However, their findings have only been reported in a press release and have not yet been published in a peer-reviewed journal. According to another statement, the company is currently conducting a Phase 2 trial for older adults, followed by a trial for children and adolescents. Sinovac previously used the same technology to create approved vaccines for hepatitis A, hepatitis B and swine flu, bird flu and the virus that causes hand, foot and mouth disease, according to STAT News.

Moderna/National Institute of Allergy and Infectious Diseases.

As previously reported by Live Science, the vaccine candidate (mRNA-1273) was developed by U.S. biotech company Moderna and the National Institute of Allergy and Infectious Diseases (NIAID) and is the first vaccine to be tested on humans in the United States.

Moderna’s vaccine relies on a technology that has not been used in any approved vaccine to date: a genetic material called messenger RNA (mRNA). While conventional vaccines are made up of weakened or inactive viruses or proteins from those viruses to trigger an immune response, mRNA vaccines are made up of genetic material that teaches cells to build these viral proteins (in this case, coronavirus spiking proteins) on their own. Both conventional and mRNA vaccines trigger an immune response in the body so that if a person is naturally exposed to a virus, the body can quickly recognize it and fight it.

These mRNA vaccines have several advantages, including being faster and easier to manufacture than traditional vaccines, which can take time to develop because scientists must grow and inactivate entire pathogens or their proteins, according to National Geographic. However, mRNA vaccines may cause adverse reactions in the body; these types of vaccines also have stability issues and break down fairly quickly, which may limit the strength of immunity, according to National Geographic.

A group of researchers reported in a 2018 review published in Nature Reviews Drug Discovery that mRNA vaccines have proven to be “promising alternatives” to traditional vaccines, but “until recently, their use has been limited by erratic and inefficient” delivery into the body.” Recent technological advances have now largely overcome these issues, with multiple mRNA vaccine platforms for infectious diseases and several cancers already demonstrating encouraging results in animal models and humans.”

Last week, Moderna published promising early results from a phase 1 trial of 45 participants in the New England Journal of Medicine. The participants were divided into three groups and given low, medium and high doses of the vaccine. After receiving two doses of the vaccine, all participants developed neutralizing antibodies at levels higher than the average of recovered COVID-19 patients, according to Live Science.

The vaccine appeared to be safe and generally tolerable, but more than half of the participants had some side effects (similar to those that can occur with annual flu shots), including fatigue, chills, headaches, muscle pain, and pain at the injection site. Some participants in the medium and high dose groups developed a fever after the second injection. One who received the highest dose experienced a “severe” episode of fever, nausea, dizziness and fainting, according to the report. But this participant felt better a day and a half later. In the upcoming trial, participants will not be given such a high dose of the drug.

According to Live Science, Moderna’s Phase 2 trial is still ongoing, and on July 27, the company began a Phase 3 trial in the United States. The trial is expected to enroll about 30,000 participants by the end of the summer – and the first results of the trial could be available by November, according to the report.

In April, HHS pledged up to $483 million for accelerated development of the Moderna vaccine in its “Operation Warp Speed” campaign.

Canstar Biosciences/Beijing Institute of Biotechnology
CanSino Biosciences has collaborated with the Beijing Institute of Biotechnology to develop a vaccine candidate using a weakened adenovirus. Unlike the Oxford vaccine, which relies on an adenovirus that infects chimpanzees, CanSino Biosciences uses an adenovirus that infects humans.

Along with Moderna, the group also published the results of their phase 2 trial in the Lancet on July 20. The trial, conducted in Wuhan (where the first case of coronavirus appeared), involved 508 participants who were randomly assigned to receive one of two different doses of the vaccine or a placebo.

The study also found no serious adverse events, although some people reported mild or moderate reactions, including fever, fatigue and injection site pain. According to the study, about 90 percent of the participants had a T-cell reaction and about 85 percent had neutralizing antibodies.

“The results of these two studies bode well for the Phase 3 trial, and the vaccine must be tested in a larger population of participants to assess its effectiveness and safety,” wrote Naor Bar-Zeev and William J Moss of the Johns Hopkins International Center for Vaccine Access in an accompanying commentary in The Lancet, referring to the study and the publication in the same Journal of the Oxford Vaccine Study.” Overall, the results of the two trials were broadly similar and very promising.”

According to Reuters, they are now looking to conduct Phase 3 trials outside of China.

Sinopharm
The state-owned Sinopharm has two vaccines in the making, both of which are inactivated forms of SARS-CoV-2. These vaccines are being developed by the Beijing Institute of Biological Products and the Wuhan Institute of Biological Products. According to Reuters, Chinese state media reported yesterday that the vaccines could be ready for public use by the end of 2020.

According to Reuters, Sinopharm’s vaccines are the first inactivated vaccines to enter Phase 3 trials. The phase 3 trial, which is being conducted in Abu Dhabi, is for up to 15,000 volunteers who will receive one of two vaccine strains or a placebo. They will take two doses of the vaccine three weeks apart, according to Reuters.

Pfizer / Biotech / Fosun Pharma
Pfizer, like German biotech companies BioNTech and Moderna, is developing a vaccine that uses messenger RNA to prompt the immune system to recognize coronaviruses.

The vaccine did not cause any serious adverse events and can stimulate an immune response, according to early phase 1/2 data posted to the preprint database medRxiv on July 1, which has not been peer-reviewed. The study involved 45 patients who were given one of three doses of the candidate vaccine or placebo. None of the patients had any serious side effects, but some experienced fever (75% in the highest dose group), fatigue, headache, chills, muscle pain and joint pain.

The vaccine prompted the immune system to make neutralizing antibodies at levels 1.8 to 2.8 times higher than in recovering patients, the study found. Pfizer later announced the new results (in a press release, so the study was not peer-reviewed), and the vaccine also prompted the production of T cells specific to the new coronavirus.

This week, the Trump administration announced a $1.95 billion contract with Pfizer and BioNTech to produce at least 100 million doses of the vaccine (and up to 500 million more as needed) by the end of the year if it proves its vaccine is safe and effective. According to the New York Times, Americans will receive the vaccine for free. Earlier, according to a statement, the two companies announced an agreement with the U.K. to provide 30 million doses of the vaccine if the candidate is effective and approved. Pfizer is planning to begin a large-scale Phase 3 trial this month, with a regulatory review as early as October, the Times reported.