COVID-19

COVID-19: What happened to the Vaccine?

During the last count we heard, there were more than 160 potential Covid-19 vaccines in development. The race is on to find a vaccine that protects against the coronavirus SARS-CoV-2.


In less than six months, Covid-19 has devastated the globe, infecting more than 7 million people and killing more than 400,000. As per the journal Immunology study, more than half the world has been under some form of lockdown due to the contagion. People worldwide have their hopes pinned on a vaccine to tame the virus, let them return to normal, and maybe even one day eradicate the disease.

“Once we get about 70 percent of the population immune, the virus is going to have a real tough time spreading,” says John Cooke, MD, Ph.D., medical director of the RNA Therapeutics Research Program at Houston Methodist, which is collaborating with GeneOne on a Covid-19 vaccine. This is called herd immunity—when enough people are immune to the virus, there aren’t enough people to spread it, so even people who haven’t been vaccinated (or gotten sick) are protected.

The race is on to find that vaccine. According to the Milken Institute, there are more than 160 COVID-19 vaccines in various development stages around the world. Hopefully, more than one will pan out.

Here’s a timeline of milestones so far and what we hope to see in the future.

What really is a vaccine?

Vaccines stimulate the body’s immune system to fight intruders, explains Judy Wang, Ph.D., life sciences solutions consultant at Signals Analytics. This analytics platform looks at data to uncover trends.

Traditionally, this is done by exposing the body to weakened or inactive forms of the [disease-causing] pathogen, so that body begins to create antibodies to fight the real pathogen,” she says.


“The body can retain this type of ‘immune memory,’ so that if a person is exposed to the pathogen again, the immune response can be quickly turned on.”


Nowadays, in addition to weakened or killed versions of pathogens, new technologies are in play. Two major concerns in developing any new vaccine are safety and efficacy (how well it works). And in the case of Covid-19, we want the vaccine fast, Dr. Cooke says. As yesterday.

December 31, 2019

On the last day of 2020, Chinese health authorities reported a cluster of mysterious pneumonia cases in Wuhan, China, to the World Health Organization (WHO). No one knew what was causing the illness, although the outbreak seemed to have originated at a Wuhan market that was closed the next day.

On January 2, the Chinese Center for Disease Control and Prevention and the Chinese Academy of Medical Sciences received samples from four patients. It embarked on finding the cause, according to Xinhua News Agency. Identifying a pathogen—a disease-causing germ or virus—would be vital to diagnosing, treating, and, eventually, developing a vaccine.

January 12, 2020

Less than two weeks later, Chinese scientists had not only identified the cause as a novel coronavirus but had also decoded its genetic sequence, which they made available publicly on January 12. Among other things, knowing the series helps researchers understand how the virus might be mutating or changing over time, says Johns Hopkins University. If a vaccine changes dramatically and rapidly, a vaccine can become outdated and no longer useful. So far, we have good news on this front. There’s no evidence that the virus would change so much that the vaccine wouldn’t work, says Kathryn M. Edwards, MD, professor of pediatrics at Vanderbilt University Medical Center in Nashville, Tennessee.

Publication of the genetic sequence is just one instance of what Dr. Cooke characterizes as “a very open and rapid sharing of data and information” related to Covid-19 and “an incredible spirit in the medical community” people join forces to combat this new threat.

February 24, 2020

Within 42 days of publication of the genetic sequence, the biotech company Moderna had made its first vaccine, an mRNA (messenger RNA) vaccine, says Dr. Cooke, who is also chair of Houston Methodist’s department of cardiovascular sciences. That vaccine was shipped to the National Institutes of Health (NIH) for Phase 1 studies. (Phase 1 clinical trials are small and designed only to determine if a drug or vaccine is safe for humans, not that it works.)

RNA and DNA vaccines use components of genetic code to stimulate that immune response, says Dr. Wang. So far, the FDA has not approved any RNA or DNA vaccines, says Dr. Wang. Experts are investigating many other types of vaccines for Covid-19, including a live attenuated vaccine, meaning it uses a weakened version of the virus to stimulate antibodies and protein subunit vaccines and nucleic acid vaccines of which use part of the virus to produce antibodies.

Most of these vaccines, including the Moderna one, target the trademark “spike” proteins on the novel coronavirus.

March 24, 2020

Sixty-three days after the sequencing was made available, Moderna announced that the first volunteer had been inoculated with the new vaccine, launching the Phase 1 portion of the trial, an unprecedented timeline in the world of vaccine development. Typically, vaccines take at least ten years to develop and go through several phases of clinical trials in humans after first being tested in animals.

Phase 1 looks mainly at safety issues, according to the Food and Drug Administration (FDA). Stage 2 through 4 clinical trials look at whether the vaccine works and any relatively rare side effects that might show up only in larger numbers of people. The tests can be sped up by combining some of the phases and, in the case of a Covid-19 vaccine, special regulatory measures.

“At least 10 vaccine candidates are already being tested in humans,” says Dr. Edwards. “Most are in Phase 1. The projection for Phase 3, at least in the United States, is the beginning of July and August. It’s hoped that some of the information on whether the vaccines are effective will be discerned in about six months.”

May 18, 2020

Accompanied by much fanfare, Moderna announced interim results for the Phase 1 study: The vaccine produced “neutralizing antibodies” in all participants (eight people) and appeared safe.

Not all antibodies are created equal. “The kind of antibody you want to have the body make in response to your vaccine is an antibody that will tie up the virus and get rid of it,” says Dr. Cooke. “Those are neutralizing antibodies.”

The vaccine needs to bind with the virus so that it interferes with it getting into human cells. It’s not clear yet if this vaccine produces that response, Dr. Cooke adds. That means producing immune-system cells to target the virus.

The Future: Regulatory Issues

In regular times, the regulatory approval process for vaccines (and drugs and devices) is, says Dr. Wang, “an incredibly difficult and lengthy process, with a high failure rate. Once a vaccine makes it through clinical trials—and only about 6 percent do—it needs to be licensed by the FDA. Fortunately, the agency has introduced measures to speed up the process.

In pandemic terms, the process is running at almost warp speed. (In one case, approval for a diagnostic test took just three hours, according to the data company Statista and the World Economic Forum, through vaccines will be different.)

Despite the unprecedented time frame, researchers don’t seem to be sacrificing safety and efficacy issues. “I think that we have a lot of experience evaluating vaccines for whether they’re safe and effective,” says Dr. Edwards.

“The timeline is pretty truncated but it doesn’t mean we’re not going to be looking at the same safety concerns. Data will be carefully collected and assessed.”

Manufacturing Roadblocks

The next challenge is producing enough vaccines, ideally 7 billion doses, one for every human on the planet. And it will need to happen fast. Manufacturing needs will depend on what kind of virus we end up with, say an RNA vaccine or a weakened version of the coronavirus.

Various solutions have been put forward, including growing virus particles in repurposed tobacco plants. Then there’s the money. The Coalition for Epidemic Preparedness Innovations (CEPI) estimates that it will take $2 billion to develop and make enough vaccines. Various organizations, including CEPI, have stepped up to pledge portions of that.

Researchers are working in a lab at the Yisheng Biopharma company in Shenyang, China, on June 10, 2020. – The company is one of a number of Laboratories in China trying to develop a vaccine for the COVID-19

Distribution

Distribution is next: How to get it out to people and, importantly, who should be given priority. Again, this is an unanswered question and may differ depending on the country, says Dr. Edwards. In the United States, “recommendations for use and who is given priority usually comes from the Advisory Committee on Immunization Practices (ACIP) at the Centers for Disease Control and Prevention (CDC).

They already have a working group [starting to determine] who will be prioritized,” explains Dr. Edwards. There have been concerns that the vaccines won’t be distributed equitably and won’t be shared among nations.

According to the WEF, to stymie Covid-19, the vaccines will have to reach as many places as the virus does, meaning virtually everywhere. Many experts want high-risk folks and frontline healthcare workers to get priority.

Vaccine Candidates

Moderna (working with the National Institute of Allergy and Infectious Diseases or NIAID) seems to be leading the pack, at least in terms of speed, but what about others? BioNTech and Pfizer are also working on an RNA vaccine currently in Phase 1/2 studies. The University of Oxford is working with AstraZeneca on an adenovirus vaccine (a new technique using genetically engineered cold viruses) to begin Phase 3 trials.

Many of the major pharmaceutical companies have joined forces, including Sanofi and GlaxoSmithKline. The Wuhan Institute of Biological Products and the Beijing Institute of Biological Products are working with Sinopharm (based in China) on inactivated vaccines, which use killed pathogens. And the list goes on.

When are we going to have a Vaccine?

And that brings us to the million-dollar question: When will we be able to walk into a clinic or pharmacy and receive a safe and effective vaccine for Covid-19? Estimates vary.


“NIAID Director Anthony Fauci has released a well-publicized timeline of 12-18 months before a vaccine can be available for public use, so the soonest we are looking at would be in a year,” says Dr. Wang.


Some have suggested the end of the year as a target date, but Dr. Cooke doesn’t think we’ll see a vaccine until, at the earliest, early 2021.” Bear in mind that all this effort all over the world does not guarantee the arrival of a vaccine ever.

But experts are optimistic. “The early results are promising,” says Dr. Cooke. “The pace of vaccine development has been unprecedented, so much faster than ever before.”

And will it get us back to ‘normal’?

The right vaccine could eliminate a disease (as happened with smallpox), says Dr. Cooke. Realistically, though, normalcy will depend on how effective the vaccine is and how safe (although vaccines are typically very safe). “If it’s a home run, we could get everybody back to their old lives,” says Dr. Edwards.

Anything less than a home run may restore some routines but not all. In general, vaccines vary in their effectiveness. The flu shot reduces the odds of getting sick by between 40 percent and 60 percent, depending on the year, says the CDC. However, a new flu vaccine has to be developed each year to fight the respiratory virus as it circles the globe. On the other hand, two doses of the MMR vaccine (covering measles, mumps, rubella) are about 97 percent effective, and new vaccines and annual repeats aren’t necessary.

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