Covid-19 variants: beyond Omikron

Vaccination breakthroughs as a success strategy for Sars-CoV-2

When the increase in SARS-CoV-2 infection subsides, the virus has to compensate by overcoming immune responses, Kobe says. For example, if a mutation or series of mutations halves the ability of a vaccine to prevent transmission, it will greatly increase the number of available hosts in a population. Kobe says it’s hard to imagine that future increases in infections could produce the same batch.

This evolutionary path — toward bypassing immunity and moving away from increased infection — is common in well-established respiratory viruses such as influenza, says Adam Kucharski, a sports epidemiologist at the London School of Hygiene and Tropical Medicine. The easiest way for a virus to start spreading new epidemics is to evade immunity over time. This is similar to what we observe with seasonal coronaviruses.”

Laboratory experiments and sequencing of circulating variants identified a mixture of spike protein mutations that impair the efficacy of neutralizing antibodies induced by infection and vaccination. Variants with these mutations, such as beta, made vaccines less effective, but did not break protection, especially against severe disease.

Compared to other variants, Omikron has many of these mutations. Bloom’s preliminary analysis suggests that these mutations may render some parts of the virus undetectable by antibodies. But these are just hypotheses. It takes lab experiments and epidemiological studies to fully understand the effects of these mutations.

Fly Immune Infection Costs

However, developing mutations that evade immune responses such as antibodies can also have evolutionary costs. A mutation that avoids antibodies can reduce the ability of the virus to recognize and bind to host cells. The region of spike binding – the primary target for neutralizing antibodies – is relatively small, says Jason McClellan, a structural biologist at the University of Texas at Austin. The region cannot be changed indefinitely in order to continue to perform its main task of binding to the ACE2 receptors of host cells.

It’s also possible that repeated exposure to different versions of Spike – through infection with different strains of the virus, vaccines, or both – can eventually build up immunity that’s hard to beat with Sars-CoV-2. Mutations that override the antibody response of some people are unlikely to do the same in the entire population. T-cell-mediated immunity – another part of the immune response – appears to be more resistant to changes in the virus genome.

Bloom says such restrictions could slow the progression of SARS-CoV-2 toward vaccination breakthroughs, but perhaps not prevent them. McClellan says there’s already clear evidence that some mutations of this type can turn off antibodies, but that they don’t have any major developmental flaws. “The virus will always be able to mutate parts of the height.”

T-cell immunity is believed to be more robust

How SARS-CoV-2 develops in terms of immunity also has an impact on how it becomes endemic in the future. According to Kucharski, there is no consistent baseline level of infection. “Many people have a flat horizontal line on their heads, which is not the case with endemic infections. Instead, the virus is more likely to cause epidemics of varying size, such as influenza and most other common respiratory infections.”

To be able to predict what these outbreaks will look like, scientists are studying how quickly a new population is exposed to infection, Kucharski says, and whether this is primarily due to viral evolution, reduced immune responses, or the birth of new babies. Without immunity to the virus. “Small changes that unlock a specific part of the population previously exposed to new infections are probably the most likely evolutionary path,” Rambaut says.

Small changes that render a particular part of a previously exposed population susceptible to re-infection are perhaps the most likely evolutionary path.
(Andrew Rambaut, Evolutionsbiologe)

The most optimistic — but most likely — future for Sars-CoV-2 will be to follow the measles path. Infection or vaccination provides lifelong protection, and the virus is most common in newborns. “Even a virus like measles, which cannot evolve to bypass immunity, is still around,” Bloom says.

There is more possibility, but still relatively hope, in parallel with Sars-CoV-2 which is a pathogen called respiratory syncytial virus (RSV). Most people are infected in the first two years of their lives. RSV is a major cause of hospitalization in children, but most cases in children are mild. Low immunity and viral evolution mean that new strains of RSV are spreading over the planet every year, infecting adults in large numbers but causing mild symptoms thanks to childhood exposure. If SARS-CoV-2 follows this path — bolstered by vaccines that offer powerful protection against dangerous diseases — “it will essentially become a children’s virus,” Rambaut says.

The flu presents another scenario – actually two. Influenza A virus, which is responsible for epidemics of seasonal influenza in the world every year, is characterized by the rapid development and spread of new variants that can evade the immunity brought about by previous strains. The result is seasonal epidemics, driven primarily by its spread among adults, who can still develop severe symptoms. Influenza vaccines reduce disease severity and slow transmission, but the rapid development of influenza A means that vaccines are not always well-compatible with circulating strains.

However, if the SARS-CoV-2 virus evolves to evade immunity more slowly, it may resemble influenza B. The slower rate of change of this virus compared to influenza A means that it is transmitted largely through infection in children, who are less immune than adults.

How often should vaccines be modified?

How quickly the SARS-CoV-2 virus develops in response to the immune system will also determine whether and how often the vaccines need to be updated. in a Pre-published September 2021 Bedford and his team found evidence that SARS-CoV-2 evolves much faster than seasonal coronaviruses and even faster than influenza A, which is called the major circulating form H3N2. Bedford believes that the change in the SARS-CoV-2 virus will slow over time. “But I don’t know if it will be like H3N2, where you have to update the vaccine every year or two, or if it will be something worse,” he says.

And while other respiratory viruses, including seasonal coronaviruses like 229E, present several potential futures for Sars-CoV-2, the virus could head in a very different direction, according to Rambaut and others. The massive spread of the delta variant and the rise of Omikron—fueled by the uneven distribution of vaccines to low-income countries and minimal control measures in some rich countries such as the United States and the United Kingdom—provide fertile ground for further sudden jumps in the evolution of SARS-CoV-2.

There can be multiple directions in which the virus can evolve – and the virus has not yet stabilized
(Andrew Rambaut, Evolutionsbiologe)

For example, a document released in July by a UK government scientific advisory group addressed the possibility that SARS-CoV-2 could become more severe through recombination with other coronaviruses or bypassing existing vaccines. Continued circulation in the tanks of animals such as mink or white-tailed deer carries a greater potential for sudden changes.

The future of SARS-CoV-2 may remain in the hands of the people. If as many people as possible are vaccinated while vaccines are still highly effective, the virus can be prevented from triggering the changes that lead to a new wave. “There can be many directions in which the virus could evolve, and the virus has not yet stabilized,” Rambaut says.