Strain reduces immune response
California’s new dominant variant is more transmissible, less drug resistant, study finds
California’s more infectious strain of the COVID-19 virus is now the dominant variant in the state and has been proven to thwart protective antibodies used in vaccines and therapeutics, according to a new UC San Francisco study.
In response, the Centers for Disease Control and Prevention has labeled the California strain a “variant of concern,” joining a designation shared by strains first identified in Great Britain, South Africa and Brazil.
Within just the past six months, it has exploded in prevalence. By the end of January, when the study was completed, the variant represented more than 50% of genomes sequenced from infected people tested at UCSF’s hospitals and clinics, Alameda County’s community sites and Santa Clara County’s congregate facility, community and acute care sites.
With a reproductive rate that doubles more than once a month, its prevalence is now likely higher.
Vaccines will likely remain effective against the variant, according to lead investigator Dr. Charles Chiu of UCSF, whose lab is collaborating with the state’s Department of Public Health to seek cases of the new variant.
But its behavior is worrisome. Scientists found a twofold decrease in neutralizing antibody activity against the California variant. The South African variant, which is proved to elude vaccines, causes a sixfold reduction. Antibody levels are a marker of protection.
The growing prevalence of this more contagious pathogen, combined with its ability to reduce immune protection, means it must be watched, Chiu said.
“I don’t think it’s going to lead to a ‘vaccine breakthrough,’ where the vaccine doesn’t work,” he said. “But this study gives us some initial idea of the infectivity and the potential resistance to neutralizing antibodies for a variant that, up until now, has not been studied. This is key information that we need.”
The discovery comes as hospitalizations and deaths from the coronavirus are on a continued downswing in California, reflecting the continued health practices — from distancing and masking to getting vaccinated — that experts warn are vital to control the virus as it evolves.
The so-called California variant has been found to be about 20% more infectious than the original virus, according to the study.
Previous studies linked the variant, called B.1.427/B.1.429, to increased risk of severe disease and death, as well as longer stays in intensive care units and the need for mechanical ventilation.
The variant has been reported in other states but most of the cases are in California, Nevada and Arizona, according to outbreak.info, a website that tracks epidemiological data around the world.
Also concerning are the results from new lab studies: There was a 6.7-fold decrease in antibodies in the blood of 7 out of 8 people who had received treatment with monoclonal antibodies or convalescent plasma.
“What that means is it’s likely that there’s some element of what we call ‘antibody escape’ — where, if you were infected before, you will not necessarily be protected against reinfection,” said Chiu.
What the findings mean for how well the vaccine and treatments will protect real people from the variant is hard to tell.
Antibody levels are only one part of the immune response; the vaccines also trigger T cells, scientists say.
It is possible that vaccines trigger such high levels of antibodies that their efficacy would drop only slightly. Immunity is not binary, turning on or off; instead, it’s on a spectrum.
But the new findings raise concerns about a potentially higher risk of reinfection among vaccinated people. The risk of reinfection might be highest for people who produced low levels of antibodies after vaccination.
A drop in antibodies also could have more subtle effects, such as immunity waning a bit faster, according to the journal Science.
Like all viruses, the COVID-19 pathogen makes tiny changes in its genome as it reproduces. Understanding this evolution — and especially which mutations can change its behavior — is essential for estimating the threat of new strains.
The virus’s genetic makeup, stored in a single strand of RNA, determines whether it might suddenly turn resistant to medicine, or whether a vaccine is protective or futile.
The U.S. Department of Health and Human Services recently halted shipments of an Eli Lilly treatment, called bamlanivimab, to California, Nevada and Arizona, citing concerns that it may be less effective against the strain.
Officials said that another COVID-19 therapy made by Eli Lilly, a combination of bamlanivimab and another drug, etesevimab, can still be ordered. Early results show the drug combination may significantly reduce the risk of hospitalization and death. A different antibody treatment made by Regeneron Pharmaceuticals was also not affected by the HHS action.
The California variant has four unique mutations, including three that change the shape of the virus’s spiked protein, which the virus uses to attach to cells and slip inside. That is likely why the variant is more contagious.
It is not known exactly where the variant emerged. Back in January, a key mutation, called L452R, was found in 53% of 630 COVID-19 cases in San Francisco’s Mission District.
No coronavirus variants currently rise to the U.S. government’s highest threat level, “variant of high consequence.” Coronavirus strains shown to significantly reduce vaccine effectiveness would fall under that category.