Recovering From COVID-19 Doesn't Necessarily Mean You're Immune—So How Would a Vaccine Work?

There are many things we still do not know about the new coronavirus that has so far infected over 3.2 million people. This includes whether people are immune after contracting the virus and, if so, how long this immunity lasts—questions that are hugely important for scientists racing to create a vaccine.

Vaccines work by introducing antigens into the body so the immune system can learn which antibodies to create in case of future attacks. Antigens include substances given off by a virus. As vaccines rely on the body's immune response to prevent us from developing disease, how are scientists approaching vaccine research when questions remain on our immunity to the coronavirus?

The uncertainty around immunity was evidenced last Friday when the World Health Organization (WHO) warned countries against issuing so-called immunity passports to those who have caught the COVID-19 virus. The U.N. body stated: "There is currently no evidence that people who have recovered from COVID-19 and have antibodies are protected from a second infection."

The WHO later acknowledged the brief had promoted "some concern," and clarified it was not stating that people who have caught the coronavirus are not immune. Rather, it meant that most people who are infected will likely have an antibody response "that will provide some level of protection," but the level of protection and how long it will last is currently unknown.

"So far, no studies have answered these important questions," it said.

Experts told Newsweek it is indeed difficult to predict what immunity will look like so soon after the pandemic started.

Aubree Gordon, associate professor in the Department of Epidemiology at the University of Michigan School of Public Health, told Newsweek: "There hasn't been enough time for people to get infected, for us to document their immunity and then to follow them forward in time to see if they can get infected again in the future."

In general, we know that the spike proteins that viruses use to invade our cells are exposed, so tend to be good targets for the immune system, Gordon explained. We also know that the spike protein on coronaviruses produce an immune response, she said.

SARS-CoV-2, the virus that causes COVID-19, is a member of the large coronavirus family of germs which includes the SARS-CoV virus that causes severe acute respiratory syndrome (SARS), and MERS-CoV, which triggers Middle East Respiratory Syndrome (MERS). People who have had SARS and MERS appear to retain antibodies to their viruses for several years.

"Certainly we can extrapolate from what we know about endemic coronaviruses and from SARS and MERS, but ultimately this virus may be different and continued efforts will be needed to assess the length of immune protection," she said.

One important unknown, William Keevil, professor of environmental healthcare at the U.K's University of Southampton told Newsweek, is whether those who have mild or no symptoms have a higher or lower antibody response compared to those who have suffered severe symptoms. "Until we have mass antibody testing underway, we cannot answer that question," he said.

With over 200,000 having died from COVID-19, according to Johns Hopkins University, scientists across the world are working hard to create a vaccine to prevent it from infecting more people and spreading further.

Sanjay Mishra, a staff scientist at the Vanderbilt University Medical Center in Tennessee, told Newsweek that the immunity gained against natural infection from coronaviruses is generally weak and transient.

If natural immunity is not protective, "then it would greatly diminish the likelihood that we would be able to develop an effective vaccine," Gordon said.

A good example of a virus that does not generate protective immunity—and for which we do not have a vaccine—is respiratory syncytial virus, Jeremy Rossman, honorary senior lecturer in virology at the University of Kent, told Newsweek. The virus generally causes a mild respiratory illness with symptoms similar to the common cold, but can be life-threatening for babies and those in other high-risk groups.

The way the virus interacts with and suppresses the immune system during infection means that while the body can usually fight off the infection, it cannot remember how to protect from re-infection, Rossman said. This has made it very difficult to design a vaccine that successfully protects against the virus.

Fortunately, vaccines do not solely depend on triggering an antibody response.

As well as causing the body to create antibodies against a virus, vaccines can also trigger a cellular response, Ohid Yaqub, senior lecturer at the Science Policy Research Unit at the University of Sussex, told Newsweek. Currently, dozens of candidates based on different approaches are being developed around the world.

"Antibodies work by preventing cells getting infected, whilst the cellular response works by mopping up already-infected cells," he said.

Typically, what are known as subunit vaccines—where a piece of a germ, like a surface protein, is used to confer immunity—are better at triggering an immune response in the body and are thought to be better at preventing infection, according to Yaqub. There are many subunit vaccines which are "seeking to trigger a response from both arms of the immune system," he said.

Whole virus vaccines, such as live-attenuated approaches using a weakened form of the germ, are meanwhile thought to be better at triggering a cellular response. Even if whole virus vaccines do not prevent infection, they may be useful for keeping severe symptoms at bay.

"A scenario where antibodies do not confer much protection would be a problem, and we'll see vaccine developers change tack if that happens," Yaqub said. "It's really good to have a diversity of approaches being pursued in parallel. We don't yet know how well they will trigger immune responses in terms of cellular response and antibody response."

Peter Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston and co-director of the Texas Children's Hospital Center for Vaccine Development, and colleagues are currently working on what is known as a receptor binding domain recombinant protein vaccine.

They are betting on teaching the immune system to fight SARS-CoV-2 based on the genetic code of the virus's spike protein which it uses to bind to a receptor in our bodies.

Speaking to Newsweek, he said "our vaccine and others should work." Their approach is based on a decade of work on the virus that causes SARS and some new data on SARS-CoV-2, he said.

If scientists clear the obstacles they face, vaccines could offer herd immunity, with up to 90 percent of the population protected, according to Keevil. But vaccines are not fail-proof, he said.

"Pathogens can begin to mutate, which may alter the target site of the vaccine and make it less effective—hence the reason why we need a different flu vaccine each winter, depending on the circulating strain of influenza," he said.

Although there have been no "serious" mutations which would jeopardize vaccine development, Keevil said: "There is no reason why mutations could not occur in that part of the virus genome which the vaccine(s) depends on. These mutations can be random events and we don't know when and where they will occur."

Another problem with vaccines is that they do not always work with just one shot, for instance the flu jab, and they do not protect everyone equally. "Old people respond less well and may need repeated booster injections—this and the duration between booster injections is yet to be ascertained," said Keevil.

Yaqub suggested one scenario is that the antibody response is only short term. "A transient response might be addressed by boosting after a few months in an effort to prolong the protective effect," he said. "The downside is that of course this would put pressure on the manufacturing side, since each person would need more than one dose."

Hotez also acknowledged that boosters might be necessary for his team's vaccine.

But as Jeremy Farrar, a member of the U.K. government's Scientific Advisory Group for Emergencies, told Newsweek at a media briefing last week: "If we have a vaccine that gave much of the world protection for 12 months, or two years, that would be a massive breakthrough."

Such a vaccine would "buy us critical time with the world better protected than we are today, so that would be success as we see it at the moment," he said.

According to Gordon, it is important to remember that some form of immunity is still useful, and cannot only protect against infection but also severe disease.

"In addition, immunity can impact transmission in a similar manner, if someone cannot get infected they cannot transmit, however, if someone has some immunity but still gets infected it may reduce their ability to transmit the infection, but may not prevent all onward transmission," she said.

Rossman was optimistic about the road ahead. "Unfortunately, there is no simple answer here. The key factor here is how many people are working on this project.

"We have some of the best vaccine development teams and platforms developing and testing a wide range of candidates. This gives me a lot of hope that we will be able to develop a vaccine, the only question is how long that will take."

Mishra said: "The fate of vaccine trials has several hurdles to cross and nothing is guaranteed, but that should not stop us from trying."