The first anti-HIV drug brought dying patients back from the brink. But when excited doctors ran to get the miracle drug for new patients, the miracle melted away. In each patient, the drug only worked for a while.
It turned out that the drug was very good at killing the virus, but the virus was even better at developing resistance to the drug. A spontaneous mutation in the genetic material of the virus prevented the drug from doing its job, and then the mutant viruses were able to replicate wildly despite the drug, making the patients sick again.
It took another decade before scientists found evolution-safe therapies.
Could the same thing happen with a COVID-19 vaccine? Could a vaccine that is safe and effective in the initial trials continue to fail because the virus develops out of trouble?
As evolutionary microbiologists who have studied a poultry virus that has developed resistance to two different vaccines, we know that such a result is possible. We also think we know what it takes to stop it. COVID-1
The history of vaccine resistance
For the most part, humanity has been lucky: Most human vaccines have not been undermined by microbial development.
For example, the smallpox virus was eradicated because it never found a way to develop around the smallpox vaccine, and no strain of measles virus has ever emerged that can strike the immunity triggered by the measles vaccine.
But there is one exception. A bacterium that causes pneumonia managed to develop resistance to a vaccine. Developing and replacing that vaccine with another was expensive and time consuming with seven years between the initial emergence of resistant strains and the licensing of the new vaccine.
There have been no other defects in human vaccines yet, but there are indications that viruses, bacteria and parasites may develop or develop in response to vaccination. Escape mutants capable of evading vaccine-induced immunity are regularly seen in the microbes that cause hepatitis B and pertussis.
For such human diseases as malaria, trypanosomiasis, influenza and AIDS, vaccines have been difficult or impossible to develop because the microbes that cause these diseases develop so rapidly. In agricultural environments, animal vaccines are often undermined by viral development.
What would it look like?
If SARS-CoV-2 develops in response to a COVID vaccine, there are several directions it can take. The most obvious is what happens to the flu virus.
Immunity works when antibodies or immune cells bind to molecules on the surface of the virus. If mutations in these molecules on the surface of the virus change, antibodies cannot grip them as tightly and the virus is able to escape.
This process explains why the seasonal flu vaccine needs to be updated every year. If this happens, a COVID vaccine will need frequent updating.
But evolution may be going in other directions. It would be better for human health, for example, if the virus develops in a stealth state, perhaps by reproducing slowly or hiding in organs where immunity is less active.
Many pathogens that cause hardly any noticeable chronic infections have taken this tack. They avoid detection because they do not cause acute illness.
A more dangerous path would be if the virus evolved a way to replicate faster than the immunity generated by the vaccine. Another strategy would be for the virus to target the immune system and suppress vaccine-induced immunity.
Many microbes can survive inside the human body due to their exquisite ability to disrupt our immune system. If SARS-CoV-2 has ways to even partially disable human immunity, a COVID vaccine may favor mutants that make it even better.
Before COVID came together, we compared two vaccines that continue to work with vaccines that have been undermined by pathogen development.
It turns out that truly evolutionary vaccines have three functions. First, they are very effective in suppressing viral replication. This stops further transmission. No replication, no transmission, no evolution.
Second, evolutionary 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 being targeted. However, if many sites are attacked at once, immune release requires the presence of many separate escape mutations simultaneously, which is almost impossible.
This has already been shown in the SARS-CoV-2 laboratory. There, the virus rapidly developed resistance to antibodies targeted to a single site, but struggled to develop resistance to a cocktail of antibodies, each targeting several sites.
Third, development-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 evolutionarily safe?
Approximately 200 COVID vaccine candidates are in various stages of development. It is too early to know how many of them have these evolutionary security features.
Fortunately, we do not have to wait until a licensed vaccine finds out. A little extra effort during vaccine trials can go a long way in finding out if a vaccine will be evolutionarily safe.
By washing people who have received the experimental vaccine, researchers can tell how far virus levels have been suppressed. By analyzing the genome of any virus in vaccinated humans, it may be possible to see evolutionary flight in action. And by taking blood from vaccinated people, we can find out in the laboratory how many places on the virus are attacked by vaccine-induced immunity.
It is clear that the world needs COVID vaccines. We believe it is important to pursue those who continue to work. Probably many candidates in the current portfolio will. Let’s find out which ones are in clinical trials, and go with them.
Vaccines that provide only temporary relief leave people vulnerable and take time and money to replace. They may also reject other vaccines if viruses develop that are resistant to several vaccines at once.
Today, the world has insecticide-resistant mosquitoes and crops, herbicide-resistant weeds, and an antibiotic-resistance crisis. No need for history to repeat itself.
Andrew Read, Evan Pugh University Professor of Biology and Entomology, Eberly Professor of Biotechnology, Director, Huck Institutes of the Life Sciences, Penn State and David Kennedy, Assistant Professor of Biology, Penn State.
This article is republished from The Conversation under a Creative Commons license. Read the original article.