Here are the most promising coronavirus vaccine candidates out there

Using materials from weakened cold viruses to snippets of genetic code, scientists around the world are creating dozens of unique vaccine candidates to fight the novel coronavirus — and they’re doing it at unprecedented speeds.

A little over six months after the World Health Organization (WHO) first alerted the world to a mysterious cluster of pneumonia cases in Wuhan, China, 166 candidate vaccines are in development to prevent the coronavirus that caused the disease (called COVID-19), according to WHO. Most of the candidate vaccines are in preclinical stages, meaning they are still being tested on animals or in the lab, but a handful of them have reached human trials. 

Such clinical trials are broken up into three to four stages, with earlier stages (phase 1/phase 2) examining the safety, dosage, and possible side effects and efficacy (how well it works at fighting the pathogen) of the candidate vaccine in a small group of people, according to the Food and Drug Administration (FDA). The key to getting a candidate vaccine approved, however, is showing promising results in the more advanced phase 3 trial. 

Related: Coronavirus live updates

In phase 3 trials, researchers test the efficacy of the vaccine, while monitoring for adverse reactions in hundreds to thousands of volunteers. The FDA then approves the vaccine if trials show it is safe and effective, and the vaccine’s benefits outweigh its risks, according to the Centers for Disease Control and Prevention (CDC). Five coronavirus vaccine candidates have started recruiting for, or are undergoing, phase 3 trials, according to WHO. Here are the most promising of those candidates:

University of Oxford/AstraZeneca

A sign for the COVID-19 vaccine trial conducted by the University of Oxford

(Image credit: Shutterstock)

The vaccine currently called ChAdOx1 nCoV-19, popularly known as the Oxford vaccine, is being developed by the British university in collaboration with pharmaceutical company AstraZeneca.  The vaccine is made from a weakened version of a common cold virus, called an adenovirus, that infects chimpanzees. Researchers genetically altered the virus so that it couldn’t replicate in humans and added genes to code for the so-called spike proteins that the coronavirus uses to infect human cells. In theory, the vaccine will teach the body to recognize these spikes, so that when a person is exposed, the immune system can destroy it, according to a previous Live Science report

Researchers previously tested this vaccine in rhesus macaque monkeys and found that it did not prevent the monkeys from becoming infected when deliberately exposed to the coronavirus, but did prevent them from developing pneumonia, suggesting that it was partially protective, according to a study published May 13 to the preprint database BioRxiv.

In April, researchers began testing the vaccine on people and published early results from their phase 1 and still-ongoing phase 2 trials on July 20 in the journal The Lancet. The vaccine didn’t cause any serious adverse effects in participants but did prompt some mild side effects, such as muscle ache and chills. The vaccine spurred the immune system to produce SARS-CoV-2-specific T-cells — a group of white blood cells important in the fight against pathogens — and neutralizing antibodies, or molecules that can latch onto the virus and block it from infecting cells, according to the report.

Phase 3 trials have already begun in Brazil and will enroll up to 5,000 volunteers. Another phase 3 trial is expected to enroll an additional 10,500 people in the U.K. and 30,000 in the U.S., according to the Oxford vaccine trial webpage and The New York Times. The team at Oxford has also expressed interest in conducting challenge studies on humans, meaning they would deliberately infect low-risk volunteers with the virus, either alongside phase 3 trials or after they are complete, according to The Guardian.

The U.S. Department of Health and Human Services (HHS) announced that it would give up to $1.2 billion to AstraZeneca to accelerate the vaccine development process and to help the company manufacture at least 300 million doses of the vaccine — if it proves safe and effective — as early as October 2020, according to a statement. This is part of the Trump administration’s Operation Warp Speed, an initiative that aims to deliver 300 million doses of a safe and effective vaccine by January of 2021, according to HHS.

The coronavirus uses spike proteins (seen on its surface here) to invade human cells.

The coronavirus uses spike proteins (seen on its surface here) to invade human cells. (Image credit: Shutterstock)

Sinovac Biotech

Another candidate vaccine, called (PiCoVacc) and being developed by Beijing-based Sinovac Biotech, protected rhesus macaque monkeys from infection with the novel coronavirus, according to a study published July 3 in the journal Science. The company, having already shown the vaccine to be safe and effective in early clinical trials, is recruiting for a phase 3 clinical trial with 8,870 participants in Brazil, according to clinicaltrials.gov.

This vaccine is made up of an inactivated version of the SARS-CoV-2 virus. Inactivated vaccines are the dead version of the pathogen that causes the disease (as opposed to weakened viruses which are live vaccines), according to the U.S. Department of Health and Human Services (HHS). Inactivated viruses such as the flu vaccine or the hepatitis A vaccine, are typically not as protective as live vaccines and might require booster shots over time, according to the HHS. In contrast, the Oxford vaccine is a weakened form of a live vaccine, which can create long-lasting immune responses but tends to be riskier for people with weakened immune systems or other health problems, according to the HHS.

Sinovac began phase 1/phase 2 trials (involving 743 healthy adults) in April in the Jiangsu province of China. They gave participants two doses of the vaccine, two weeks apart, and reported that the vaccine didn’t cause any serious adverse events, according to a statement. Study authors also said more than 90% of participants had developed neutralizing antibodies to the vaccine two weeks after receiving the second dose. However, their results have only been reported in a press release and haven’t yet been published in a peer-reviewed journal. The company is now conducting a phase 2 trial on elderly adults and will later conduct one on children and adolescents, according to another statement. Sinovac previously used the same technology to create approved vaccines for hepatitis A, hepatitis B and swine flu, avian flu and the virus that causes hand, foot and mouth disease, according to STAT News

Moderna/National Institute of Allergy and Infectious Diseases

Moderna is developing an mRNA-based coronavirus vaccine.

(Image credit: Shutterstock)

This candidate vaccine (mRNA-1273), developed by U.S. biotech company Moderna and the National Institute of Allergy and Infectious Diseases (NIAID), was the first to be tested on humans in the U.S., according to a previous Live Science report

Moderna’s vaccine relies on a technology that hasn’t been used in any approved vaccines to date: a piece of genetic material called messenger RNA (mRNA). Traditional vaccines are made up of weakened or inactive viruses, or proteins of those viruses, to trigger an immune response; mRNA vaccines, on the other hand, are made up of genetic material that teaches cells to build these viral proteins themselves (in this case, the coronavirus’ spike protein). Both traditional and mRNA vaccines trigger an immune response in the body such that if a person is naturally exposed to the virus, the body can quickly recognize and fight it. 

These mRNA vaccines have several advantages, including being quicker and easier to manufacture than traditional vaccines, which can take time to develop because scientists have to grow and inactivate entire pathogens or their proteins, according to National Geographic. mRNA vaccines might also be more durable against pathogens that tend to mutate, such as coronaviruses and flu viruses. However, mRNA vaccines can cause adverse reactions in the body; these types of vaccines also have problems with stability, breaking down quite quickly, which might limit the strength of immunity, according to National Geographic.

mRNA vaccines have shown to be “a promising alternative” to traditional vaccines, but “their application has until recently been restricted by the instability and inefficient” delivery into the body, a group of researchers reported in a 2018 review published in the journal Nature Reviews Drug Discovery. “Recent technological advances have now largely overcome these issues, and multiple mRNA vaccine platforms against infectious diseases and several types of cancer have demonstrated encouraging results in both animal models and humans.”

mRNA vaccines teach cells how to make the spike protein (the mRNA is translated to amino acids, the building block of proteins inside what's called the cell's ribosome).

mRNA vaccines teach cells how to make the spike protein (the mRNA is translated to amino acids, the building block of proteins inside what’s called the cell’s ribosome). (Image credit: Shutterstock)

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

The vaccine appeared safe and generally well-tolerated, but more than half of the participants had some side effects (similar to side effects that can happen from the annual flu shot) including fatigue, chills, headache, muscle aches and pain at the injection site. Some participants in the middle- and high-dose groups experienced a fever after the second injection. One person who received the highest dose experienced a “severe” fever, nausea, lightheadedness and an episode of fainting, according to the report. But this participant felt better after a day and a half. Such high doses won’t be given to participants in upcoming trials.

Moderna has already started its phase 2 trial and plans to start a phase 3 trial with 30,000 participants at the end of the month — a trial that is expected to be completed by October, according to the report.

In April, the HHS, under Operation Warp Speed, committed to spending up to  $483 million for the accelerated development of Moderna’s vaccine.

CanSino Biologics/Beijing Institute of Biotechnology

CanSino Biologics, in collaboration with the Beijing Institute of Biotechnology, developed a candidate vaccine using a weakened adenovirus. Unlike the Oxford vaccine, which relies on an adenovirus that infects chimpanzees, CanSino Biologics is using an adenovirus that infects humans. 

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

This study also didn’t find serious adverse events, though some reported mild or moderate reactions including fever, fatigue and injection site pain. Around 90% of the participants developed T-cell responses and about 85% developed neutralizing antibodies, according to the study. 

“The results of both studies augur well for phase 3 trials, where the vaccines must be tested on much larger populations of participants to assess their efficacy and safety,” Naor Bar-Zeev and William J Moss, both part of John Hopkins’ International Vaccine Access Center, wrote in an accompanying commentary in The Lancet referring to this study and the Oxford vaccine study published in the same journal. “Overall, the results of both trials are broadly similar and promising.” 

They are now looking to conduct a phase 3 trial outside of China, according to Reuters.

Sinopharm

The state-owned China National Pharmaceutical Group (Sinopharm) has two vaccines in the making, both inactivated forms of SARS-CoV-2. These vaccines were developed by the Beijing Institute of Biological Products and the Wuhan Institute of Biological Products. These vaccines could be ready for the public to use by the end of 2020, Chinese state media reported yesterday, according to Reuters

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

Pfizer/BioNTech/Fosun Pharmaceutical

Pfizer and German biotechnology company BioNTech are, like Moderna, developing a vaccine that uses messenger RNA to prompt the immune system to recognize the coronavirus.

The vaccine didn’t cause any serious adverse events and could spur an immune response, according to early phase 1/phase 2 data released to the preprint database medRxiv on July 1 and that hasn’t yet been peer-reviewed. The study involved 45 patients who were given one of three doses of either the candidate vaccine or a placebo. None of the patients had serious side effects, but some developed side effects such as fevers (75% in the highest dose group), fatigue, headaches, chills, muscle pains and joint pain. 

The researchers found that the vaccine prompted the immune system to make neutralizing antibodies at levels 1.8 to 2.8 times higher than those found in recovered patients, according to the study. Later, Pfizer announced new results (in a press release, so the findings aren’t peer-reviewed) that the vaccine also prompted the production of T-cells specific to the novel coronavirus. 

This week, the Trump administration announced a $1.95 billion contract with Pfizer and BioNTech to produce at least 100 million doses of their vaccine by the end of the year if it proves to be safe and effective (with up to 500 million doses more as required). Americans would receive the vaccine for free, according to The New York Times. Previously, the two companies announced an agreement with the U.K. for 30 million doses of the vaccine candidate if it works and is approved, according to a statement. Pfizer is planning for a large-scale phase 3 trial to start this month and regulatory review for as early as October, according to the Times.

Originally published on Live Science.

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