Profound immune escape by SARS-CoV-2 XBB.1 even after 4 vaccine doses

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In a recent correspondence published in The Lancet Infectious Diseases journal, researchers in Germany assessed the neutralization sensitivity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) XBB.1 lineage.

Co-infection with different SARS-CoV-2 lineages can lead to the recombination of the distinct viral genomes and the creation of new and recombinant SARS-CoV-2 lineages. First detected in India in January 2022, the recombinant XBB lineage is spreading rapidly throughout Europe and Asia. The XBB lineage was formed due to the recombination of two SARS-CoV-2 Omicron variant sublineages, namely BM.1.1.1 and BJ.1. The breakpoint of this novel lineage is located within the spike protein gene, which facilitates viral entry into the host cell and comprises the target of neutralizing antibodies. So far, five primary XBB sublineages have evolved, with XBB.1 accounting for most coronavirus disease 2019 (COVID-19) cases.

Correspondence: Neutralisation sensitivity of the SARS-CoV-2 XBB.1 lineage. Image Credit: Corona Borealis Studio / ShutterstockCorrespondence: Neutralisation sensitivity of the SARS-CoV-2 XBB.1 lineage. Image Credit: Corona Borealis Studio / Shutterstock

About the study

In the present study, researchers reported the efficiency with which the SARS-CoV-2 XBB.1 lineage can enter the host cell and evade antibody-mediated neutralization.

The team employed pseudovirus particles (pp) carrying the SARS-CoV-2 spike protein that served as a suitable model for studying SARS-CoV-2 entry in the host cell and its subsequent neutralization. Particles that were pseudotyped with the ancestral SARS-CoV-2 B.1 (B.1pp) or the Omicron BA.5 (BA.5pp) lineage were utilized for comparison. Furthermore, the team analyzed the neutralization sensitivity of XBB.1pp by monoclonal antibodies (mAbs) and the mAb cocktails currently used clinically or in development for COVID-19 therapy or prophylaxis.    

The team also analyzed the sensitivity of XBB.1pp to neutralization by COVID-19 vaccination or vaccination along with breakthrough infection. Furthermore, plasma samples from triple-vaccinated persons having breakthrough COVID-19 infections during BA.5 prevalence in Germany were assessed.


The study results showed that in comparison to B.1pp, the BA.5pp showed 2.2-fold higher efficiency in entering Vero cells and 5.3-fold higher efficiency in entering 293T cells. On the other hand, the efficiency of BA.5pp entering Calu-3 cells was 1.9-fold lesser than that of B.1pp. Additionally, particles that carried the XBB.1 spike protein (XBB.1pp) displayed remarkably decreased efficiency in cell entry compared to BA.5pp for all the cell lines assessed. However, the entry efficiency of B.1pp and XBB.1pp was comparable to that of Vero and 293T cells.

The team also noted that all the analyzed mAbs and mAb cocktails effectively neutralized B.1pp while XBB.1pp was neutralized by only sotrovimab and S2H97. Also, the efficiency of XBB.1pp neutralization decreased by over 10 times compared to B.1pp neutralization. Additionally, plasma obtained from triple-vaccinated persons had almost no XBB.1pp neutralization activity. On the other hand, B.1pp neutralizing activity was high while that against BA.5pp was intermediate. The plasma samples of triple-vaccinated persons with breakthrough infection showed high B.1pp neutralizing activity, moderate BA.5pp neutralizing activity, and low XBB.1pp neutralizing activity.

Overall, the study findings showed that the SARS-CoV-2 XBB.1 lineage has an exceptionally robust antibody evasion activity. The researchers believe that the finding that XBB.1pp was not neutralized by mAbs highlights the need for novel mAbs for COVID-19 treatment along with additional therapeutic options for locations with high cases of XBB lineage infections. 

Journal reference:
Bhavana Kunkalikar

Written by

Bhavana Kunkalikar

Bhavana Kunkalikar is a medical writer based in Goa, India. Her academic background is in Pharmaceutical sciences and she holds a Bachelor's degree in Pharmacy. Her educational background allowed her to foster an interest in anatomical and physiological sciences. Her college project work based on ‘The manifestations and causes of sickle cell anemia’ formed the stepping stone to a life-long fascination with human pathophysiology.


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  1. Stephanie Last Stephanie Last United States says:

    So basically you are bound to get COVID no matter what you do?  Imagine that.  Now if we could get the mad scientists to stop mixing and matching to create a deadly virus as transmissible as omicron for research purposes we could maybe acknowledge this is gonna be with us forever like the flu..  China really needs to stop messing with viruses.  Seems the tyrant is experiencing trouble from the people and gives the gift of COVID when they protest.   I get the feeling that some doctors and some scientists know exactly what to expect in the future from COVID and it's mutations but they don't want to tell people they messed up. Even though the knowledge about the mRNA shots is out there and slowly coming out in studies from other countries for some reason they are still pushing that shot.    It's not an immunization and it's not a vaccine and no matter how many times you change the definition for a word there will always be someone who remembers the actual definition.     These people would be impossible to play a fair game with because they change the rules mid game and never tell any one else they changed it.  That's why the word rare sounds like few and far between or almost never but now it seems to mean you have a 50 50 chance of  injury from this shot and most people believe in these shots when it was known to not keep you from getting COVID and spreading it in the beginning.  Immunizations make you immune to what ever it's made from.   The risks outweigh the benefits tenfold .   And if studies were done on people who haven't had the shot that caught COVID added in with the "vaccinated" you would see that more people without the shot who get COVID never get admitted to the hospital because it's not the same virus any more.   Some off them never even know they have it.  That shot is not necessary.   I think people would flip if they found out what mRNA is and what it's function is because from a moral standpoint most of them believe that realm of science is immoral or playing with fire and they think that so much so they made it illegal to do experiments with it in humans didn't they?  Even going as far as to say stem cells shouldn't be experimented with either even though the two things are totally   different conversations.  But what do I know?

  2. Bob van de Voort Bob van de Voort Netherlands says:

    What I never get, is why leave out unvaccinated people, especially unvaccinated people who had 1 or more infections.

    Are they scared of the results not putting the vaccines in a favourable light in comparison to natural immunity?

    Like it would such a simple extra step....

  3. David Marcus David Marcus United Kingdom says:

    I've had all the jabs and been more ill for longer for the first time in my life. So what the hell are these injections doing for me? People i know who have not had any jabs are healthier than i am and not keep coming down with these so called new cold viruses. A cold, cough, sore lungs that go on for weeks into a month or longer that's worse than when i had covid. Yes i even had that after jabs. So, no i don't feel safe of protected. Only now think "what the hell is realky6going on here". Are all those regarded as being "surplus to the requirements of "The SYSTEM" just being slowly killed off? God help us from the unscrupulous.

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
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