Is a Covid-19 Vaccine Actually Possible?

ince the earliest days of America’s Covid-19 crisis, Anthony Fauci, the White House’s top coronavirus expert and director of the National Institute of Allergy and Infectious Diseases, has said that — best case scenario — a vaccine could be ready within a year to 18 months.

In an interview published on June 8 in the Journal of the American Medical Association (JAMA), Fauci stated that if one of the several vaccines currently in trial proves effective, hundreds of millions of doses could be ready by early 2021. “I’m cautiously optimistic that, with the multiple candidates that we have with different platforms, we’re going to have a vaccine that shows a degree of efficacy that would make it deployable,” he said.

Fauci’s mention of different “platforms” may not have meant much to lay readers. But the scientific community is intensely aware of these next-gen vaccine-development technologies and processes that Fauci was talking about. The vaccines that these new platforms aim to create are easier to produce quickly and in volume, which is one reason why the usual “decade or more” timeline for vaccine development has shrunk to less than two years.

But two of the new platforms that are generating the most hype and optimism are also largely unproven. “They’re so new, in fact, that a commercial vaccine has never been brought to market using either one of them,” says Mark Cameron, PhD, an associate professor in the Department of Population and Quantitative Health Sciences at the Case Western Reserve University School of Medicine in Cleveland.

Cameron says that he’s “as hopeful as anyone else,” but that some big hurdles still stand between humanity and a safe, effective Covid-19 vaccine.

The new platforms that are leading the way are fundamentally different in that they do not require developers to physically grow live Covid-19 in cells.

Genes at the center of the new vaccine “platforms”

Historically, the development and production of any vaccine has relied on real, lab-grown viruses. These viruses tend to be either weakened, inactivated, or stripped down to their benign parts before being introduced into a person’s body, where they trigger a protective immune response.

Some institutions are working on these sorts of old-school vaccines for Covid-19. But the new platforms that are leading the way are fundamentally different in that they do not require vaccine makers developers to physically grow live coronavirus in cells.

“The one people are hearing a lot about is the mRNA platform,” says Amesh Adalja, MD, a pandemic expert and senior scholar at the Johns Hopkins Center for Health Security. Adalja explains that mRNA stands for “messenger RNA,” a type of molecule that helps convert a DNA’s blueprint into an actual, functional protein molecule. The mRNA platform is designed to isolate a virus’s “gene of interest” — the one that codes for the protein that the immune system reacts to — print its genetic sequence, and then formulate it so that it can be injected into a person, he says. Once injected, the idea is that the body’s cells will take up the mRNA and start making proteins that trigger a protective immune response.

“We want as many shots on goal from as many different directions as we can get.”

The mRNA platform is one of several new “genetic vaccines” that all work in more or less the same way. “Whether DNA or mRNA, you inject these genetic vaccines, which go into the cells and use [the cells’] machinery to make the so-called spike protein,” says Paul Offit, MD, chair of vaccinology at the University of Pennsylvania’s Perelman School of Medicine.

Offit says that the spike protein allows the coronavirus to attach itself to healthy cells, which is how the virus takes root and spreads. Genetic vaccines are designed to expose the immune system to this spike protein — but not the virus — so that it will generate antibodies and other defenses that will block the virus from setting up shop. An mRNA Covid-19 vaccine from the drug company Moderna, in partnership with the National Institutes of Health, is now in Phase II clinical trials. Several other closely related “genetic vaccines” are in various stages of development, Offit says.

Apart from genetic vaccines, the other much-hyped new vaccine platform is known as the adenovirus platform, which works somewhat like genetic vaccines in that it uses a person’s cells to make proteins that generate an immune response. “With these, you’re infecting people with a known virus, but one with the original genetic payload ripped out and replaced with genetic instructions to make the coronavirus proteins that generate an immune response,” says Derek Lowe, PhD, a drug-development researcher who writes about — and sometimes works with — the pharmaceutical industry. Like Moderna’s mRNA vaccine, some adenovirus vaccines have performed well in Phase I clinical trials.

Companies are already producing these new vaccines

Should one or more of these vaccines work, the world needs them to be ready and available as soon as possible. In an effort to ensure that happens, many companies — with massive financial support from the U.S. government and others — are already producing these new vaccines. “This is a big financial risk, but the thinking is that some of these vaccines will work, and if they do, we’ll be ready to get them to people quickly,” says Drew Weissman, MD, PhD, a professor of medicine at UPenn and one of the creators of the mRNA platform. “I think these new platforms are going to be able to solve the current pandemic, and will also be useful in prevention for any future pandemics that may appear.”

While expectations are high that one or more effective vaccines will be ready for wide deployment by early 2021, nothing is certain. “I’m optimistic about these efforts, but you have to ask what can go wrong,” Lowe says.

“If we have to go back to a traditional vaccine, I think we go back to that original statement by Anthony Fauci and a number of others, which is that a vaccine is 12 to 18 months away.”

So what can go wrong? He mentions some establishedvaccine risks or side effects, which range from injection-site soreness or mild illness to, in vanishingly rare cases, Guillain-Barre syndrome (GBS) — a disorder in which the immune system mistakenly attacks the outer lining of healthy cells. “GBS is very rare and most people survive it and recover, but not everyone does, and vaccines can set it off,” he says.

Apart from these familiar risks, Lowe says it’s possible that the new vaccine platforms could come with new and unexpected risks — though he’s confident that Phase II and III clinical trials would identify those before the vaccine is widely deployed. “Early on, people were really worried about something called antibody-dependent enhancement, or ADE, where the vaccine can actually make a pathogen more virulent in a person,” he says. “But we know what to look for, and so far none of the research has shown these ADE mechanisms.

Strength in numbers

While new platforms are raising the odds that medical science will develop a Covid-19 vaccine quickly, Lowe says that hundreds of research teams and initiatives are exploring all manner of vaccine development — new and old. “We want as many shots on goal from as many different directions as we can get,” he says. Even if the mRNA or other newer platforms fail, he says, this shouldn’t set timelines back more than a few months.

Others agree. “If we have to go back to a traditional vaccine, I think we go back to that original statement by Anthony Fauci and a number of others, which is that a vaccine is 12 to 18 months away,” says Case Western Reserve’s Cameron. “So instead of early 2021, we’re talking fall of 2021.”

But even some of those who believe that we’ll have a vaccine in the next year or so say that nothing is certain. “Nature gives up its secrets slowly, and I’m sure there are surprises ahead for us,” says UPenn’s Offit. “We need to stay humble and not rush things.”