In a 1988 article on pandemics Joshua LederbergThe Nobel Prize winner and President of Rockefeller University reminded the medical community that Darwin’s laws are as important as Pasteur’s vaccines on infectious diseases.
As medicine fights bacteria and viruses, these organisms continue to be subject to mutations and develop new properties.
Lederberg advised vigilance: “We have no guarantee that the natural evolutionary competition of viruses with the human species will always be the winner.”
With the advent of seemingly safe and effective vaccine candidates, humanity seems to be the winner again this time around, albeit with a terrible loss of life.
But vaccines are not going to stop this coronavirus development, according to Pennsylvania State University’s David A. Kennedy and Andrew F. Read, specialists in virus resistance to vaccines, recently wrote in PLoS Biology. Instead, they could even drive new evolutionary changes.
There is always the possibility that the virus, while small, could develop resistance to a vaccine in what researchers refer to as “viral escape”. They urge the vaccine effects and virus response to be monitored just in case.
“Nothing we say suggests we are slowing down vaccine development,” said Dr. Kennedy. An effective vaccine is of the utmost importance. “But let’s make sure it stays in effect.”
Vaccine manufacturers could use the results of nasal swabs taken from volunteers during the trials to look for genetic changes in the virus. The test results do not have to stop or slow the introduction of the vaccine. However, if recipients of the vaccine had changes in the virus that those who received the placebo did not, it would indicate “the potential for resistance to develop,” which the researchers should continue to monitor.
There are several reasons to be optimistic that the coronavirus won’t become vaccine resistant. A few years ago, Dr. Kennedy and Dr. Read an analysis of the difference between drug resistance and vaccine resistance. Neither bacteria nor viruses develop resistance to vaccines as easily as they do to drugs, they wrote. Despite years of use, the smallpox vaccine did not lose its effectiveness, nor did the measles or polio vaccines.
Antibiotics, on the other hand, can quickly become unusable than bacteria and others Pathogens such as viruses and fungi develop defenses. And resistance to other drugs also builds up.
The reasons have to do with the basic principles of evolution and immunity. The two main differences are that vaccines generally work earlier than drugs and that the natural immune responses they promote are usually more diverse and open to attack. A drug can be tightly targeted and sometimes attack a metabolic pathway or biochemical process.
For most drugs, the virus or bacteria have already multiplied in the patient’s body. If a variant better survives the drug’s attack, it will continue to grow and may be passed on to another person. A combination of drugs as in H.I.V. Treatment, may be more effective because it triggers a multilevel attack
Vaccines, on the other hand, work early, before the virus begins to multiply and possibly change in a patient’s body. So there are no new flavors as forged in the heat of a drug attack to grow and spread from the infected person.
Vaccines give the body’s immune system a glimpse into the virus, and then the immune system builds a broad attack. For example, a person’s immune system can produce 100 different antibodies after a tetanus shot.
However, some vaccines drive viruses to develop resistance, Dr. Kennedy and Read noted this in their 2015 article. A vaccine has stopped Marek’s disease, a disease in chickens that is commercially important. But the virus could still infect the chickens. It replicated and spread without disease and quickly became resistant.
In humans, a type of bacteria that cause pneumonia bacteria developed resistance to a vaccine when the bacteria naturally recombined with existing strains that were naturally resistant. A vaccine against hepatitis B produced antibodies that targeted only a small part of a protein – a loop of nine amino acids that is tiny in relation to the protein. No broad attack was launched. A pertussis vaccine also appeared to increase resistance. It worked to stave off the disease, but it only targeted a few proteins and was ineffective in stopping the infection and transmission of the virus.
The coronavirus vaccines currently under development use various methods to get the immune system to respond. Some coronavirus vaccines developed or used in Russia and China use whole virus particles that are inactivated or weakened to trigger an immune system response.
Many other vaccine candidates, such as those from Pfizer and Moderna, which are due to be tested for the first time by the Food and Drug Administration in December, are intended to induce the immune system to only react to part of the coronavirus, the so-called spike protein, which seems to offer fewer destinations.
But Dr. Kennedy said that wasn’t necessarily a problem. “A vaccine based only on the spike protein can trigger a broad immune response,” he said, “because there are multiple sites on the spike protein that strong neutralizing antibodies can bind to.”
Although these are the first vaccines to use RNA particles to tell cells to make a viral protein, other vaccines use parts of the virus rather than the whole. So far, said Dr. Kennedy, there was no evidence that any type of vaccine was more likely to lead to resistance. “We have seen vaccine resistance evolve to many different types of vaccines,” he said, “but there are also many examples of each of these vaccines that have not shown resistance.”
Resistance can also develop in ways that are independent of how a vaccine works. There may already be variants of the coronavirus that are less susceptible to the effects of vaccines. This gave rise to concern Denmark announces that it will stamp out all of its mink because a variant of the virus had appeared in the mink which in very preliminary laboratory tests showed that some antibodies were less effective against the virus.
Concern has subsided since the Danes announced the problem. Scientists and the World Health Organization said they hadn’t seen any evidence that the variant would affect vaccines under development.
But Denmark is still planning to kill all the mink in the country following the resignation of a minister who announced the cull too early and a legislative debate that appears to lead to approval of the cull.
The road to a coronavirus vaccine
Interesting facts about vaccines
Confused by all of the technical terms used to describe how vaccines work and study? Let us help:
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- Adverse event: A health problem that occurs in volunteers in a clinical trial with a vaccine or drug. An adverse event is not always caused by the treatment tested in the study.
- Antibody: A protein produced by the immune system that can attach to a pathogen such as the coronavirus and prevent it from infecting cells.
- Approval, Licensing, and Approval for Emergency Use: Medicines, vaccines and medical devices cannot be sold in the US for no profit approval by the Food and Drug Administration, also known as Licensing. After a company has submitted the results of clinical studies to the F.D.A. For testing purposes, the agency decides whether the product is safe and effective. This process usually takes many months. If the country faces an emergency – like a pandemic – a company can file an application instead Emergency approvalthat can be granted much faster.
- Background rate: How often does the general population experience a health problem called an Adverse Event? To determine whether a vaccine or drug is safe, researchers compare the rate of adverse events in one study to the background rate.
- Effectiveness: A measure of the effectiveness of a treatment in a clinical trial. To test a coronavirus vaccineFor example, researchers compare how many people in the vaccinated group and the placebo group received Covid-19. The actual effectiveness of a vaccine may differ from its effectiveness in a study.
- Phases 1, 2 and 3 studies: Clinical trials typically take place in three phases. Phase 1 studies typically involve a few dozen people to determine whether a vaccine or drug is safe. In Phase 2 studies, involving hundreds of people, researchers can try different doses and take more measurements of the vaccine’s effects on the immune system. Phase 3 studies involving thousands or tens of thousands of volunteers determine the safety and effectiveness of the vaccine or medicine by waiting to see how many people are protected from the disease it is supposed to be fighting.
- Placebo: A substance with no therapeutic effect that is widely used in clinical trials. For example, to see if a vaccine can prevent Covid-19, researchers can inject the vaccine into half of their volunteers while the other half are given a placebo with salt water. You can then compare how many people are infected in each group.
- Post-market surveillance: The surveillance that occurs after a vaccine or drug has been approved and regularly prescribed by doctors. This monitoring usually confirms that the treatment is safe. Rarely, side effects are noted in certain groups of people that were overlooked during clinical trials.
- Preclinical Research: Studies that take place prior to the start of a clinical trial typically include experiments that test a treatment on cells or animals.
- Viral vector vaccines: A type of vaccine that uses a harmless virus to deliver immune-stimulating ingredients into the human body. Viral vectors are used in several experimental Covid-19 vaccines, including that of AstraZeneca and Johnson & Johnson. Both companies use a cold virus called adenovirus as a vector. The adenovirus carries coronavirus genes.
- Test protocol: A series of procedures that must be performed during a clinical trial.
And scientists say caution makes sense in such situations. When a virus bounces from humans to animals and back again, like mink does, there are more opportunities for changes in viral RNA, changes that can lead to resistance.
University of Pittsburgh researchers have discovered a type of mutation that has not previously been seen in coronaviruses, raising new concerns about the evolution of vaccine resistance.
When looking for mutations, researchers mainly focused on flipping one genetic letter into another – a type of mutation known as substitution. However, Paul Duprex and his colleagues found that the viruses mutating in a chronically infected patient changed differently: they lost sets of genetic letters.
Typically, a mutation that erases a genetic letter is catastrophic to a virus. Our cells each read three genetic letters to select a new building block for a growing protein. Deleting a genetic letter can completely mess up the instructions for a viral protein so that it cannot form a functional form.
Dr. However, Duprex and his colleagues found that the patient’s coronaviruses could lose genetic letters and still remain viable. The secret: the viruses have lost genetic letters in groups of three. Instead of destroying the genetic recipe for a viral protein, the mutations cut out one or more amino acids.
As much as Dr. Duprex despises the pandemic, it is difficult not to admire the elegance of these mutations. “It’s so cool, it’s brilliant,” he said.
After Dr. When Duprex and colleagues found these deletion mutations in a person’s viruses, they wondered how common they were.
When they searched public databases of coronavirus genomes, they found that deletions were surprisingly widespread. “It is happening independently in different parts of the world,” said Dr. Duprex.
It turns out that all deletions only occur in one region, the spike protein. Dr. Duprex and his colleagues found that deletions in the spike gene did not prevent the coronavirus from infecting cells.
Dr. Duprex and his colleagues put their study online on November 19th. It has not yet been published in a peer-reviewed journal. Researchers are now infecting animals with deletion mutant viruses to better understand the risk they may pose to vaccines.
“Well, this paper does nothing to reduce anxiety!” Dr. Read said in an email. “This is early data that strongly suggests that the virus has the potential to evade human immunity.”
But Dr. Read and Kennedy argue that viral evolution does not necessarily make vaccines fail. Vaccine manufacturers just need to be aware of this and develop new vaccines if necessary.
And there are numerous types of vaccines under development. The first two, nearing US approval, both use a significant amount of viral RNA to train the immune system. Other vaccines that are under development use the whole virus. And different vaccines deliver the virus or part of it in different ways, which can lead to a different immune response.
