Cells from african green monkeys. Killed viruses. Spike squirrels. People have turned into factories.
To teach the human body to fight disease, you need a lot.
Creating a vaccine against coronavirus that causes COVID-19 includes many technologies and approaches.
More than 150 vaccine developments are currently underway worldwide. Eleven are already being tested in humans, and about 50 are projected to be in clinical trials by the end of the year.
Because it’s unclear which technology will be the best, scientists need to “hedge their bets” and work on all of them at the same time, said Dr. Richard Hatchett, general manager of the Epidemic Preparedness Innovation Coalition, which finances and coordinates the development of new vaccines.
“We want several vaccines under development, so we can be sure of at least some success,” Hatchett said during a recent webinar sponsored by the American Public Health Association.
The goal of any vaccine is to make the body’s immune system recognize a specific pathogen. After recognition, the immune system develops soldiers who are ready to attack if this pathogen reappears during infection. The hope that these unresponsive soldiers will protect a person from infection, or at least from a serious illness.
The Chinese government publicly unveiled the genetic sequence of the COVID-19 virus, called SARS-CoV-2, in mid-January, just a few weeks after the outbreak was detected. The move immediately sparked a wave of vaccine development projects.
Getting the sequence meant that the developers could begin to pursue what they knew would be the main goal: the so-called spike protein found on the surface of SARS-CoV-2, which gives it a special profile.
Whenever possible, they also used existing technologies, for example, using cells of African green monkeys, since viruses are efficiently propagated in them and they are well tested.
One of the problems right now is that scientists still don’t know much about what the virus does to the immune system. They develop a vaccine, not knowing, for example, how long its benefits will last or even what level of immune response they should generate.
Large clinical trials such as one is due to start in July will begin to reveal some of this missing information.
Vaccines often take 15 to 20 years. Researchers are now trying to develop a vaccine against SARS-CoV-2 in just one year to 18 months. To meet such a tight deadline, scientists have been trying for years to develop new vaccine production technologies, but they have rarely or never been used by a large number of people.
These new technologies excite some people and scare others. That’s why, according to vaccine experts, it is so important to carefully test candidate vaccines.
“We need to make sure that while accelerating vaccine development, we do not limit safety and effectiveness,” said Hatchett.
Researchers are studying several vaccine manufacturing technologies against SARS-CoV-2. Each has its own strengths and weaknesses, for example, how many images they will need to provide protection, how difficult or expensive it will be to scale them, and whether they need to be kept cold, which will not be easy to do in developing countries. World.
At a time when the world is desperately waiting for a vaccine, technologies with the longest track record, but which require the longest production time, may not be the victorious approach. But new, faster ones in development still have to prove that they can be made safe, effective and on a large enough scale to make a difference.
Here are the explanations for each of the core technologies, and several pros and cons, drawn up with the help of several experts, including Scott Weaver, director of the Institute for Infections and Human Immunity and scientific director of Galveston National Laboratory in Texas:
Whole Virus Vaccine: Live Attenuated
Strengths: Live attenuated whole viral vaccines are a powerful source of the arsenal of vaccines. Used by billions of children for decades, they have been safe and effective, for example, in combating measles, mumps and rubella combined injection, commonly known as MMR.
One dose of MMR vaccine is effective against measles by 93%, against mumps – by 78%, against rubella – by 97%, According to the US Centers for Disease Control and PreventionThe second dose increases the efficacy to 97% against measles and 88% against mumps.
These numbers mean that about 3 out of 100 people can get measles after two injections in the event of an outbreak. But people who have been vaccinated are expected to receive less infection than if they had not been vaccinated.
Weaknesses: Theoretically, these vaccines can also cause a disease that they were intended to prevent. In 2000, the United States stopped using the oral polio vaccine, which used live attenuated virus because it was able to sometimes cause the disease.
This approach can also take years when researchers struggle to find the right balance – ensuring that the virus is sufficiently weakened to be safe, but still powerful enough to elicit an effective immune response.
Mumps vaccine is considered a record for vaccine development. It took four years to developtime frames that do not make sense in the current pandemic.
Whole Virus Vaccine: Killed
Strengths: The destroyed form of the vaccine against the whole virus is considered very effective, as well as safe, because it cannot cause the disease from which it is intended to protect. Polio and rabies vaccines, among other things, use a killed version of the virus itself to stimulate the immune system.
Weaknesses: In the 1950s, a killed viral vaccine against a respiratory syncytial virus, which usually affects infants and young children, worsened the health of children when they became infected with the virus. The same thing happened in the mid-1960s with a vaccine for killed measles virus, said Paul Offit, who runs the Vaccine Education Center at the Philadelphia Children’s Hospital.
When the RSV and measles viruses, which have a specific type of protein on their surface, were killed by formaldehyde, this triggered a “weird, aberrant immune response,” he said.
According to Offit, Chinese researchers working on the SARS-CoV-2 vaccine, which has a similar surface protein, have learned this lesson. They used something other than formaldehyde to kill the virus used in their candidate vaccine.
Strengths: Protein-based vaccines include vaccines that prevent shingles, hepatitis B and human papillomavirus. SARS-CoV-2 will develop a protein-based vaccine to produce – and make the body recognize – spike protein.
These vaccines are relatively easy to manufacture, safe, and proven to provide immune responses, said Dr. Larry Schlesinger, CEO and president of the Texas Institute of Biomedical Research.
Weaknesses: According to Weaver, the effectiveness of this vaccine may require an immunostimulant that can cause side effects. For example, a newer dragee vaccine, which is a protein-based vaccine, can leave people exhausted for several days.
Another problem is longevity. It’s not clear how long the immune response to SARS-CoV-2 from a protein-based vaccine will last, Schlesinger said.
Viral vector vaccines
Strengths: Viruses are very good at invading cells and using their mechanisms to make more copies of themselves. These vaccines can stimulate a strong immune response, which means they are likely to be effective, Weaver said.
WeaknessesAccording to Weaver, with the Ebola virus vaccine, which is based on the vesicular stomatitis virus, people get a mild, flu-like illness and “don’t feel too good for a couple of days.” This means that it can not be used by people with weakened immunity.
Cold-based vaccines called adenoviruses carry their own risk. They cannot multiply as soon as they enter human cells, which means that many viral vectors are needed, Offit said. A single dose of one of these vaccines will include 1,000,000,000,000 viral particles, and Offit is worried about the idea of delivering this vaccine to tens of millions of people.
One 2014 study It has been found that people who receive the HIV adenovirus candidate vaccine feel worse than unvaccinated when infected with HIV.
In addition, many people were already susceptible and created immunity to adenoviruses. This means that the immune system will attack these viral particles before they can deliver their payload.
That’s why some researchers, including those who are developing Oxford University Candidate Vaccine, instead we work with chimpanzee adenovirus. It is believed to be safe, but not previously used in the vaccine.
Nucleic Acid Vaccines
Strengths: There is a lot of excitement in the vaccine development world around a new type of vaccine based on the delivery of strands of genetic material – essentially instructions for transforming human cells into spike protein factories.
These vaccines can be developed very quickly. The vaccine candidate of Modernity, called mRNA-1273, was ready for testing in humans just 63 days after the genetic sequence of the virus was released in January. In part, he was able to move so fast, because Modern has already tested this approach against the flu, Chikungunya and Zika.
(Although Modern’s technology is based on RNA, other nucleic acid candidate vaccines use double-stranded DNA, which is more stable. Once in human cells, it is translated into mRNA and then forms a spike protein.)
Weaknesses: This new approach to vaccine development has never been tested before in a large number of people, so there are many open questions about its safety and effectiveness.
The second dose is likely to be needed by the body to form an adequate immune response. According to Weaver, frequent boosters may be needed later if immunity is short-lived.
In addition, since nucleic acid vaccines have never been produced on a scale exceeding the scope of clinical trials, there is some concern that it will be difficult to manufacture enough to change the global pandemic. But Moderne said that by next year he will be able to take from 500 million to 1 billion doses per year.
No vaccine would be perfect Schlesinger said. All of them have their advantages and disadvantages.
But by developing the vaccine, “you can really start thinking about eliminating” a disease like COVID-19, he said.
“So we need these vaccines.”
Contact Weintraub at kweintraub @ usatoday.
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This article originally appeared in the USA TODAY: Different technologies for developing a vaccine against COVID-19