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Virus Evolution Might Undermine a Covid-19 Vaccine – however This Can Be Stopped

By Andrew Read, Penn State and David Kennedy, Penn State

The first drug for HIV brought dying patients back from the sidelines. But when excited doctors ran to bring the miracle drug to new patients, the miracle melted away. The drug only worked for a while in each patient.

It turned out that the drug could kill the virus very well, but the virus developed resistance to the drug even better. A spontaneous mutation in the genetic material of the virus prevented the drug from doing its job, and so the mutated viruses replicated wildly despite the drug, making patients sick again. It took scientists another decade to find evolutionarily safe therapies.

Could the same thing happen to a COVID-19 vaccine? Could a vaccine that is safe and effective in initial trials continue to fail because the virus evolves out of trouble? As evolutionary microbiologists who have studied a fowl virus that has developed resistance to two different vaccines, we know that such a result is possible. We also believe we know what it takes to stop it. COVID-19 vaccines could fail – but if they have certain properties, they won’t.

History of vaccine resistance

Mankind has been fortunate for the most part: most human vaccines have not been undermined by microbial evolution.

For example, the smallpox virus has been eradicated because it has never found a way to develop around the smallpox vaccine, and a strain of the measles virus has never emerged that can defeat the immunity induced by the measles vaccine.

There is one exception, however. A bacterium that causes pneumonia has managed to develop resistance to a vaccine. Developing and replacing this vaccine with another was expensive and time consuming. It was seven years between the first appearance of resistant strains and the approval of the new vaccine.

There have been no other flaws in vaccines for humans, but there is evidence that viruses, bacteria, and parasites can develop or develop in response to vaccination. Escape mutants that can evade vaccine-induced immunity are regularly seen in the microbes that cause hepatitis B and pertussis.

For human diseases such as malaria, trypanosomiasis, influenza and AIDS, it has been difficult or impossible to develop vaccines because the microbes that cause these diseases develop so quickly. In agricultural settings, animal vaccines are often undermined by virus development.

What would it look like?

If SARS-CoV-2 develops in response to a COVID vaccine, there can be different directions. The most obvious thing is what is happening to the flu virus. Immunity works when antibodies or immune cells bind to molecules on the surface of the virus. When mutations in these molecules change on the surface of the virus, antibodies cannot grab them as tightly and the virus can escape. This process explains why the seasonal flu vaccine needs to be updated every year. In this case, a COVID vaccine would need to be updated frequently.

But evolution could go in other directions. For human health, for example, it would be better if the virus developed a stealth mode, potentially multiplying slowly or hiding in organs where immunity is less active. Many pathogens that cause barely noticeable chronic infections have taken this approach. They avoid detection because they do not cause acute illness.

A more dangerous path would be if the virus developed a way to replicate faster than the immunity created by the vaccine. Another strategy would be for the virus to target the immune system and dampen the immunity induced by the vaccine.

Many microbes can survive in the human body because they are excellent at disrupting our immune system. If SARS-CoV-2 has the ability to even partially affect human immunity, a COVID vaccine might favor mutants that can do this even better.

Evolutionary Safe Vaccines

Before COVID hit the market, we compared both vaccines that continue to work with vaccines that have been undermined by the development of pathogens.

It turns out that truly evolutionary vaccines have three characteristics. First, they are highly effective in suppressing virus replication. This stops the further transmission. No replication, no transmission, no evolution.

Second, evolutionary safe vaccines induce immune responses that attack several different parts of the microbe at the same time. It is easy for a single part of the virus to mutate and escape its target. However, if many sites are attacked at the same time, many separate escape mutations must occur simultaneously for immune escape, which is almost impossible. This has already been shown in the laboratory for SARS-CoV-2. There the virus quickly developed resistance to antibodies targeting a single site, but struggled to develop resistance to a cocktail of antibodies, each targeting several different sites.

Third, evolutionary safe vaccines protect against all circulating strains so that no one else can fill the vacuum when competitors are removed.

Will a COVID Vaccine Be Evolutionary Safe?

Around 200 COVID vaccine candidates are in various stages of development. It is too early to know how many of them have these evolutionary protective functions.

Fortunately, we don’t have to wait until an approved vaccine doesn’t find out. A little extra effort during vaccine trials can go a long way in determining whether a vaccine is evolutionary safe. By wiping off people who received the experimental vaccine, scientists can see how suppressed virus levels are. By analyzing the genome of a virus in vaccinated people, it might be possible to see evolutionary flight in action. And by drawing blood from vaccines, we can find out in the laboratory how many parts of the virus are attacking the immunity induced by vaccines.


Of course the world needs COVID vaccines. We believe it is important to keep track of those who will keep working. There will likely be a lot of candidates in the current portfolio. Let’s find out which ones are in clinical trials and go with them. Vaccines that only provide temporary relief leave people vulnerable and require time and money to replace. You can also negate other vaccines in case viruses develop that are resistant to multiple vaccines at the same time.

The world today has insecticide-resistant mosquitoes and plant pests, herbicide-resistant weeds and an antibiotic resistance crisis. History doesn’t have to repeat itself.The conversation

Andrew Read, Professor of Biology and Entomology at Evan Pugh University, Eberly Professor of Biotechnology, Director of the Huck Institute of Life Sciences, Penn State, and David Kennedy, Assistant Professor of Biology, Penn State

This article is republished by The Conversation under a Creative Commons license. Read the original article.

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