Five Questions for an Immunologist on Antibodies, Testing, and a Potential Vaccine for COVID-19

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As COVID-19 (commonly known as coronavirus) continues to spread all over the world, we have shared information from MacArthur Fellows on stopping the spread of the virus, its possible biological origin(s), and much more.

But how much do we know about the possibility of developing immunity to the virus, and how much time is needed to develop a vaccine or cure?

Enter Gabriel Victora of Rockefeller University, a 2017 MacArthur Fellow and an expert in the field of immunology, who talked to us about the virus and efforts being made to reduce the global impact of the outbreak. In his work, he studies how organisms can improve their responses to infection, and his research has practical implications for the development of new and more effective vaccines, and treatments for autoimmune disorders.

Here he answers five questions about SARS-CoV-2 (note that SARS-CoV-2 is the name of the virus and COVID-19 is the disease that it causes):

Can People Become Immune to COVID-19?

A key issue in the COVID-19 pandemic is whether infection with the SARS-CoV-2 virus really induces antibodies that can protect people from reinfection, and, if so, how long this immunity will last.

Previous experience with other coronaviruses suggests that the immunity afforded by antibodies may not always be long-lived, meaning the protection afforded by natural infection may eventually recede. There is also a small chance that having low levels of antibody could actually make the disease worse in case of reinfection. This phenomenon is known as “antibody dependent enhancement,” or ADE, and is a problem in Dengue infection.

This is an important reason to be patient with vaccine development: any vaccine made has to be thoroughly tested to ensure ADE does not occur.

Can Antibodies Be Used as Drugs?

Antibodies make outstanding drugs, from the anti-snake venoms made in horses for over a century to the latest generation of anti-cancer “checkpoint blockers.” While designing these drugs can take a long time, an immediate way to leverage the potency of antibodies is to treat seriously ill patients with convalescent plasma, the cell-free component of blood from individuals recovering from COVID-19.

To ensure maximum effectiveness, convalescent plasma donors have to be screened for high levels of antibodies to SARS-CoV-2 in their blood. Early small-scale studies have shown encouraging results for this type of treatment, and multiple centers around the world are starting to implement larger-scale trials and treatment protocols. To circumvent the scalability issue, a number of academic and industry labs around the world are combing through the blood of recovering patients in search of immune cells capable of producing extremely potent neutralizing antibodies. The genetic sequence of the antibodies produced by these immune cells can then be copied and used to produce large amounts of identical antibodies in cell culture.

The better the antibody is at neutralizing SARS-CoV-2, the less of it will be required to treat disease and the lower the cost it will impose on already strained health systems. This also means there will be a lower chance that low-income countries will be priced out of deploying it at a large scale.

Is Testing the Key to Controlling the Pandemic?

Antibody tests may not be good tools to detect infection very early on. Antibodies to SARS-CoV-2 appear to arise about a week after initial infection and become reliably detectable somewhat later. By the time patients test positive, the disease is already well underway, and transmission to others may have already occurred. Many infected patients may also never develop detectable antibodies, so these tests may be of limited use for diagnosis.

But serology testing is very good at detecting who in a population has already had an infection, because the antibodies remain detectable in blood long after the virus is gone. A particularly important use of serology testing will be to determine the real prevalence of infection in a population, which can help us calculate what percentage of those infected actually die from the disease.

Several large-scale studies of this kind are already in progress. A very large number of positives in a population means the proportion of those infected that die from the virus is probably lower than currently estimated, which is good news. On the other hand, it would also mean that asymptomatic infection, and thus transmission, could be even higher than we think.

Might “Herd Immunity” Be a Faster Solution Than a Vaccine?

“Herd immunity” is the concept that infectious disease will spread in a population only if the number of susceptible individuals is sufficient for each infected person to transmit the disease to more than one other person. When enough of the population becomes immune, then the whole “herd” ceases to be susceptible to infection. For example, if each person infected with a virus goes on to infect another three people, infection rates increase exponentially. If, however, two of the three have already been exposed and are immune to the virus, overall incidence of the disease remains stable or even falls in the population. Historically the concept of “herd immunity” has been applied mostly in the context of the effectiveness of vaccination rather than natural infection.

The actual “herd immunity” threshold for SARS-CoV-2 seems to hover around 67 percent. It is much lower than, say, the measles threshold at 95 percent, but a scenario where two-thirds of the world population has been infected with a virus that causes around 1 percent of those infected to die is catastrophic. So herd immunity is far from a savior, and it is unclear that people who have recovered are even protected from reinfection.

The “herd immunity” numbers for COVID-19 mean that a potential vaccine has to be only about 70 percent effective in order to control spreading. This is substantially lower than most viral vaccines currently in clinical use, and means that a SARS-CoV-2 vaccine does not have to be stellar in order to have a major effect on the pandemic.

How and When Might This End?

Vaccines have eradicated smallpox, virtually eliminated poliomyelitis, and prevent an estimated 2 to 3 million deaths each year — so their power to curb infectious disease is uncontested. It is likely that a vaccine will play a major role in how we ultimately control this pandemic.

Given the current situation, is not unreasonable to believe that a mixture of intermittent social distancing measures and aggressive testing may keep the pandemic at bay for another one to two years while a vaccine is designed and tested. But much uncertainty remains about timelines at this point. The eradication of SARS-CoV-2 is unlikely given the abundance of animal reservoirs, but decreasing transmission to a few sporadic and controllable outbreaks is in principle feasible and would constitute a major success.

One thing to be certain of is that a large number of talented and dedicated scientists around the world are working relentlessly on developing a wide range of vaccine candidates. Sorting out which of these will be effective and safe is a lengthy process, and deploying a vaccine before these detailed studies are done is extremely risky.

But early signs from immunology and viral mutation studies indicate that a SARS-CoV-2 vaccine is more likely to be in the league of “easy” vaccines such as measles and yellow fever than in the “hard” category where H.I.V. and malaria lurk.

Learn more about how the MacArthur Foundation is responding to the COVID-19 outbreak and supporting nonprofits during the pandemic. We have also shared guidance that we have provided with regard to COVID-19 to protect the well-being of our staff, visitors to the Foundation, and people participating in MacArthur convenings. You can also review updates on the CDC website for more general information regarding the situation.

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