COVID-19 News: Hybrid Immunity And Bivalent Boosters Have Little Effect On New Omicron Sub-Lineages BQ.1.1 And BA.2.75.2 Due To Immune Imprinting!

COVID-19 News: Despite various governments, health authorities and mainstream media are trying to downplay the dire situation we are in with regards to the COVID-19 pandemic and are concealing COVID-19 statistics and also implications of long term catastrophic issues while making stupid claims that the disease is now endemic or that we have to learn to live with the SARS-CoV-2 virus or that that we have many tools to deal with the virus…..the reality is that there no such tools left expect for masking and isolation and even those might not be that effective anymore considering that fact the newer SARS-CoV-2 variants and sub-lineages have undergone evolution and conformational changes that enhances them to not only be what we would term as “Super Airborne” but are also able to withstand various extreme environmental factors from temperature, pH and humidity, in order to remain infectious in the environment for longer periods of time.


 
It has already been covered in our past COVID-19 News coverages that none of the approved monoclonal and combined monoclonal therapeutics are effective against most of the new SARS-CoV-2 variants and sub-lineages and the same can be said about all the useless U.S. FDA antivirals that are still being promoted.

https://www.thailandmedical.news/news/covid-19-news-u-s-fda-halts-usage-of-bebtelovimab-to-treat-covid-19-as-drug-is-not-able-to-neutralize-new-sars-cov-2-variants-and-sub-lineages
 
https://www.thailandmedical.news/news/u-s-fda-issues-warning-to-healthcare-professionals-that-evusheld-is-not-effective-against-newer-variants-and-soon-to-issue-another-regarding-bebtelovi
 
https://www.thailandmedical.news/news/breaking-japanese-study-finds-u-s-fda-approved-and-promoted-covid-19-drug-remdesivir-induces-cardiomyocyte-dysfunction-and-is-cardiotoxic
 
https://www.thailandmedical.news/news/breaking-covid-19-news-researchers-warn-that-molnupiravir-is-driving-rapid-evolution-of-sars-cov-2-variants-and-causing-mutations
 
https://www.thailandmedical.news/news/pharma-news-nirmatrelvir-a-key-component-of-paxlovid-blunts-development-of-antiviral-adaptive-immune-responses-in-sars-cov-2-infected-mice
 
dmedical.news/news/pharma-news-nirmatrelvir-a-key-component-of-paxlovid-blunts-development-of-antiviral-adaptive-immune-responses-in-sars-cov-2-infected-mice">https://www.thailandmedical.news/news/pharma-news-nirmatrelvir-a-key-component-of-paxlovid-blunts-development-of-antiviral-adaptive-immune-responses-in-sars-cov-2-infected-mice
 
https://www.thailandmedical.news/news/latest-danish-study-shows-that-mutations-e166v-and-l50f-e166v-on-sars-cov-2-variants-weakens-nirmatrelvir-a-component-of-paxlovid-mpro-binding
 
https://www.thailandmedical.news/news/breaking-sars-cov-2-ba-2-variant-spawning-mutations-on-its-mpro-sites-that-reduce-efficacy-of-the-antiviral-paxlovid-many-such-variants-in-america-no
 
https://www.thailandmedical.news/news/urgent-studies-needed-on-paxlovid-does-it-only-help-alleviate-symptoms-and-suppress-viral-load-for-a-while-but-does-not-help-in-total-viral-clearance
 
There are currently more than 300 of about 500 plus new variants and sub-lineages in circulation globally that have gained the right viral fitness, enhanced transmissibility and increased immune evasiveness.
 
It is only matter of time before the new variants CH.1.1, BR.2 and BN.1 that are expected to lead the next continuous virus onslaught after the BQ.1.1 and XBB sub-lineages, begins to pick up interesting mutations on the 680-699 residues of the spike that will make them more pathogenic and virulent that the Delta with its 681 mutation! Already some such emerging CH.1.1 variants have been detected in Austria!
https://www.thailandmedical.news/news/breaking-covid-19-news-scientists-identify-new-worrisome-sars-cov-2-omicron-sub-lineage-ch-1-1-spotting-delta-s-p681r-mutation-in-austria
 
Health authorities are now simply promoting the new bivalent boosters as the only means to ride off the situation with claims that these boosters prevent disease severity and mortality. (However, the number of older people and others in the vulnerable groups dying despite getting all these boosters is being to cast suspicions over these claims!)
 
A new study by German researchers from the Infection Biology Unit, German Primate Center – Leibniz Institute for Primate Research, Göttingen-Germany and Hannover Medical School-Germany has found that hybrid immunity and the new bivalent boosters have very little neutralizing effect on the new Omicron Sub-lineages BQ.1.1 And BA.2.75.2 due to immune imprinting!
 
The study findings showed that the newly emerged Omicron sub-lineages BQ.1.1 and particularly BA.2.75.2 efficiently evade neutralization independent of the immunization history.
 
Despite the fact that current monovalent and the new bivalent boosters both induce high neutralizing activity and increase neutralization breadth, BA.2.75.2-specific and BQ.1.1-specific neutralization activity remained relatively very low.
 
The study finding is in keeping with the concept of immune imprinting by initial immunization with shots targeting the ancestral SARS-CoV-2 B.1 lineage.
 
Importantly, the observation that neutralization of BA.2.75.2 and BQ.1.1 was most efficient in the cohort that had a breakthrough infection during the BA.1 and BA.2 wave and later received a bivalent booster shot, but was still less efficient than neutralization of B.1, implies that affinity maturation of antibodies and two-time stimulation with different omicron antigens might still not be sufficient to overcome immune imprinting.
 
Hence, urgent novel vaccination strategies have to be developed to overcome immune imprinting by ancestral SARS-CoV-2 antigen.
 
The study findings were published in the peer reviewed journal: The Lancet Infectious Diseases.
https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(22)00792-7/fulltext
 
The study is the first to evaluate in detail the effects of hybrid immunity and booster shots on Omicron sub-lineages.
 
Typically, COVID-19 jabs-elicited neutralizing antibodies (nAbs) target the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein to neutralize the virus.
 
Most of the currently used COVID-19 shots, including messenger ribonucleic acid (mRNA) shots, use the S protein of the strains that circulated during the beginning of the pandemic (e.g., B.1 lineage).
 
The newly developed bivalent mRNA boosters use the S proteins of both the B.1 lineage and Omicron BA.5 sub-lineage.
 
To date, they have only shown good immunogenicity against Omicron sub-lineages in mouse models!
 
Worryingly however, data on their effectiveness in humans is inadequate!
 
The German study team developed particles pseudo-typed (PP) with S protein(s) from Omicron sub-lineages to mimic antibody-mediated SARS-CoV-2 neutralization.
 
The study team then examined the effects of both jabbed and prior infection-elicited nAbs against BA.1, BA.4, BA.5, BA.4.6, BA.2.75.2, BJ.1, and BQ.1.1 Omicron sub-lineages.
 
It should be noted that early Omicron sub-lineages, such as BA.4 and BA.5, shared an identical S protein. Its sub-lineage BA.2.75.2 is circulating primarily in India, whereas BQ.1.1 is in the United States (US) and Europe. Notably, BJ.1 is the parental lineage of a highly mutated XBB SARS-CoV-2 recombinant.
 
The study team first tested neutralization sensitivity to antibodies elicited by three doses of a COVID1-9 jab regimen and subsequent monovalent and bivalent boosting.
 
They next tested the effect of COVID-19 shots plus breakthrough infection by BA.1/BA.2/BA.5 sub-lineages.
The study findings showed that the neutralization sensitivity of B.1pp was the highest, a particle pseudo-typed with the B.1 spike and next stood BA.4-5pp and BA.1pp.
 
However, the neutralization of BJ.1pp and BA.4.6pp was ~2.2 times, and that of particles pseudo-typed with BA.2.75.2 and BQ.1.1 S proteins was ~15.5 times lower than BA.4-5pp.
 
The study findings suggest that Omicron sub-lineages, BQ.1.1, in particular BA.2.75.2, possessed a higher capacity to evade nAbs elicited by diverse COVID-19 shots or boosters.
 
Interestingly, breakthrough infections by BA.1/BA.2.BA.5 in triply jabbed individuals induced 3.7 to 8.5 times higher Omicron sub-lineage neutralization.
 
But triple jabbed, BA.2/BA.1 breakthrough infection, and a subsequent bivalent booster attained the highest Omicron sub-lineage neutralization. Together, this combination induced 17.6 times more neutralization than triply vaccinated individuals with no breakthrough infection by BA.1/BA.2.
 
The research findings showed that Omicron sub-lineages BA.2.75.2 and BQ.1.1 escaped neutralization, regardless of the COVID-19 shots or booster history.
 
It was also found that mono- and bivalent boosters induced two- and 2.1-times higher neutralizing activity, respectively.
 
Furthermore, they increased neutralization breadth.
 
However, BQ.1.1 and BA.2.75.2 specific neutralization sensitivity remained on the lower side.
 
This study finding elucidates the phenomenon of immune imprinting triggered by primary vaccination with vaccines attacking the B.1 S.
 
Interestingly, the increased affinity, avidity, and anti-pathogen activity of elicited nAbs and double stimulation with two Omicron antigens could not diminish the effects of immune imprinting.
 
Hence, future inoculation strategies should pursue overcoming immune imprinting by parental SARS-CoV-2 antigens.
 
The next few months will be interesting times, as its only a matter of time before SARS-Cov-1 variants and sub-lineages that are more pathogenic and virulent emerge considering the current kinetics of the pandemic and the way it is being badly managed.
 
For the latest COVID-19 News, keep on logging to Thailand Medical News.