SARS-CoV-2 BA.2.86 is less resistant to vaccine, but may be a problem in the lung – The Ohio State University News
                            January 9, 2024
                                New research shows that the recently emerged BA.2.86 omicron    subvariant of the virus that causes COVID-19 can be neutralized    by bivalent mRNA vaccine-induced antibodies in the blood, which    explains why this variant did not cause a widespread surge as    previously feared.  
    However, the study in cell cultures showed this SARS-CoV-2    variant can infect human cells that line the lower lung and    engage in virus-host cell membrane fusion more efficiently, two    features linked to severe disease symptoms.  
    The study is published today (Jan. 8, 2024) in the journal    Cell.  
    The BA.2.86 variant of omicron is the ancestor of the currently    dominating     JN.1 and has about 60 more spike protein mutations than the    original, or parent, coronavirus, including over 30 more than    its close omicron relatives  the early BA.2 variant and the    recently dominant XBB.1.5 variant among them. These mutations    led scientists to worry that so many changes would make the    variant as tough to contain as the initial omicron outbreak in    2021-22.  
    We found that, surprisingly, despite all those 60 mutations    combined together, BA.2.86 is not as immune-evasive as the    XBB.1.5 variant, which until recently had been dominating the    pandemic for months. Thats good news, saidShan-Lu Liu,    senior author the study and a virology professor in    theDepartment    ofVeterinary Biosciencesat The Ohio State    University.  
    But BA.2.86 appears to have increased infectivity of human    lung     epithelial cells compared to all omicron variants, so    thats a little worrisome. And, consistent with infectivity, it    also has increased fusion activity with human lung epithelial    cells, said Liu, also a professor in the Departmentof    Microbial Infection and Immunity. That raises a potential    concern about whether or not this virus is more pathogenic    compared to recent omicron variants.  
    The published findings coincide with reports from the     Centers for Disease Control and Prevention that after a    brief increase in BA.2.86 infections, its derived sublineage    JN.1 rapidly gained ground in the United States, responsible    for an estimated 62% of COVID-19 cases as of Jan. 6.  
    First detected in July in Europe and the Middle East, BA.2.86    and its sublineages have since been spreading with increasing    frequency in different parts of the world. On Nov. 22, the    World Health Organization classified BA.2.86 and sublineages as    variants    of interest.  
    The Ohio State researchers analyzed neutralizing antibodies in    blood serum samples from health care professionals who had    received three monovalent vaccine doses or two monovalent    vaccines followed by one bivalent vaccine booster, and from    first responders who had COVID-19 infections during the wave    dominated by the XBB.1.5 variant. They compared the ability of    neutralizing antibodies to block infection by BA.2.86, an    XBB-derived variant known as FLip, the parent virus and several    omicron variants.  
    Overall, antibodies produced by serum from the bivalent    vaccine-dosed health care professionals were more efficient at    neutralizing BA.2.86 than they were at neutralizing other    omicron variants, including XBB.1.5. In contrast, the three    monovalent vaccines and previous XBB.1.5 infection were barely    effective in blocking infection by BA.2.86.  
    People who have had a COVID-19 infection should remember that    omicron variants are less virulent compared to prior variants    such as delta, meaning they dont make most people very sick,    Liu said. If you have less severe disease, the antibodies    generated by infection are low  almost 10-fold lower than    vaccine-induced antibodies. That is why you cannot rely on    natural infection alone for immunity.  
    While bivalent vaccine can still neutralize BA.2.86, the    efficiency is clearly reduced. Therefore, it is important to    get the newest booster vaccine, which is formulated with only    XBB.1.5 and has been shown to be effective against BA.2.86,    Liu added.  
    However, the researchers were surprised to find that a    monoclonal antibody known as S309, which has been shown to    inhibit almost all other major omicron variants, does not    neutralize BA.2.86. Molecular modeling revealed that some of    the BA.2.86 mutations in the spike protein might have changed    the conformation and rendered S309 unable to neutralize the new    variant, Liu said.  
    Additional experiments pointed to the potential for BA.2.86 to    be more likely to cause severe disease than its omicron    relatives. Researchers found BA.2.86 was more efficient at    infecting a cell line derived from the human lower airway    epithelium in the lung. Infection of these cells is greatly    facilitated through a cell surface protein, known as TMPRSS2,    to promote membrane fusion, and this protein is a known    contributor to SARS-CoV-2 infection and disease symptoms in the    respiratory tract.  
    First author Panke Qu, a graduate student in Lius lab,    conducted the cell-culture studies using pseudoviruses  a    non-infectious viral core surrounded by different SARS-CoV-2    spike proteins on the surface structured to match known    variants.  
    Because we used a pseudovirus, we need to confirm these    findings using the real virus, said Liu, also associate    director of Ohio StatesCenter for Retrovirus    Researchand a program co-director of    theViruses    and Emerging Pathogens Programin Ohio States    Infectious Diseases Institute. But from our past experience,    we know that the infectivity in human epithelial cell lines    provides very important information. The concern is whether or    not this variant, as well as its descendants including JN.1,    will have an increased tendency to infect human lung epithelial    cells similar to the parental virus that launched the pandemic    in 2020.  
    Liu noted that other labs have recently suggested that JN.1,    one of fastest-growing descendants of BA.2.86, is much more    resistant to neutralizing antibodies that are effective against    BA.2.86.  
    We know that coronaviruses are prone to viral recombination,    which can lead to new variants with huge numbers of mutations    that could have increased immune evasion but also disease    severity, he said. Thats why surveillance of the variants is    still very important, even though we are in the end of year    four of the pandemic.  
    This work was supported by anonymous donor funds, the National    Institutes of Health, the National Center for Advancing    Translational Sciences, the Glenn Barber Fellowship from Ohio    States College of Veterinary Medicine, the Robert J. Anthony    Fund for Cardiovascular Research, and Ohio States    Comprehensive Cancer Center and Center for Clinical and    Translational Science.  
    Additional co-authors, all from Ohio State, are Kai Xu, Julia    Faraone, Negin Goodarzi, Yi-Min Zheng, Claire Carlin, Joseph    Bednash, Jeffrey Horowitz, Rama Mallampalli, Linda Saif, Eugene    Oltz, Daniel Jones and Richard Gumina.  
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SARS-CoV-2 BA.2.86 is less resistant to vaccine, but may be a problem in the lung - The Ohio State University News