Viruses mutate, and the more they multiply, the more chances they have to introduce new mutations, by modifying portions of the viral genome. The virus can 'test' the effects of these mutations in their host. Some of these mutations may have little or no impact, some may be deleterious to the virus, and others may allow the virus to evade immune responses. Researchers have determined that SARS-CoV-2 can selectively delete parts of its genome. These deletions happen in a part of its genome that encodes for the spike protein, which is how the virus latches on to potential host cells.
Neutralizing antibodies prevent infection by a specific microbe. COVID-19 mRNA vaccines work by exposing the body to mRNA sequences that encode for portions of the spike protein. The body generates those protein bits, and then mounts an immune response against them, giving a vaccinated person protection against exposure to the virus. But if the virus' spike protein mutates significantly, these neutralizing antibodies may no longer attach to it, and then they cannot prevent infection.
The viral genome is being altered through deletions as well, so molecular proofreaders won't repair these mutations; they get locked in to the genome and passed on to future viral particles. The findings have been reported in Science.
"You can't fix what's not there," explained study senior author Paul Duprex, Ph.D., director of the Center for Vaccine Research at the University of Pittsburgh (Pitt). "Once it's gone, it's gone, and if it's gone in an important part of the virus that the antibody 'sees,' then it's gone for good."
This study was just a speculative pre-print a few months ago, but now the researchers have watched the virus behave this way, as new variants emerge. The variants that emerged in the United Kingdom - B.1.1.7, and South Africa - 501Y.V2, both have deletions from their sequence.
Researchers in the Duprex lab identified viruses with deletions that allowed them to avoid neutralizing antibodies in a patient with a weakened immune system; that individual was ill with COVID-19 for 74 days before dying. The virus was therefore able to tinker with its genome during that whole time, eventually generating the variant that resisted the antibodies.
The Duprex lab collaborated with scientists led by virus expert Kevin McCarthy, Ph.D., assistant professor of molecular biology and molecular genetics at Pitt to search databases of SARS-CoV-2 sequences. They found that deletions in the viral sequence kept occurring in certain places, where changes in the virus would not stop it from invading cells or replicating.
"Evolution was repeating itself," said McCarthy. "By looking at this pattern, we could forecast. If it happened a few times, it was likely to happen again."
Moving forward, it will be important to have multiple lines of defense against the virus.
"Going after the virus in multiple different ways is how we beat the shapeshifter," Duprex said. "Combinations of different antibodies, combinations of nanobodies with antibodies, different types of vaccines. If there's a crisis, we'll want to have those backups."
We also don't know exactly when the existing strains of SARS-CoV-2 will overcome the existing vaccines. There are already efforts underway to test the vaccines we have against the variants and to create boosters. Moderna claims that the antibodies that are generated by their vaccine are effective against the variant found in the UK.
"How far these deletions erode protection is yet to be determined," McCarthy said. "At some point, we're going to have to start reformulating vaccines, or at least entertain that idea."
Sources: AAAS/Eurekalert! via University of Pittsburgh, Science
