How effective are the current COVID-19 vaccines against milder infections caused by XBB variants, and how will the new vaccine formula change that?

I’m assuming this question is from last year since the XBB variants are no longer in circulation making the booster shot formulate for them particularly useless as the viral spike protein has mutated several times between now and when the XBB1.5 booster was rolled out in the fall of 2023. A couple of months after the booster roll out the JN1 variant from the BA2.86 sub lineage became the dominate variant in the U.S. and as early as January of this year constituted 98% of cases. BA2.86 had 35 mutations on the spike protein and 12 receptor binding domain mutations compared to XBB1.5 spike protein which the updated booster is formulated to create.

A serological study published in The Lancet last year analyzed neutralization activity against newly emerging subvariant BA2.86 in blood samples taken from monovalent and bivalent boosted participants found that BA.26 evades booster induced humoral immunity. The three monoclonal antibodies that worked against the parental BA2 parental subvariant had no effect against BA.26 infections have been detected in 11 countries and the subvariant’s spike protein is 30 mutations separated from the parental BA2 subvariant. BA2.86 reproductive rate is 1.3x higher than XBB1.5 and similar to the reproductive rate of EG5.

A rodent study, also published in The Lancet, found that BA2.86 (and its sub lineage) is antigenically distinct enough from XBB.1.5 (the updated booster) and prior omicron sub variants that it can evade XBB induced nABs. Using a psuedovirus, they found that BA2.86 was resistant to serum nab titer levels in mice injected with two doses of spike ModRNA shots against B1, BA.5, BQ.1.1, and XBB. Using a psuedovirus neutralizing assessment, they found that BA2.86 was just as evasive against nabs levels in two cohorts of mice (n = 81) inoculated with 3 inactivated COVID vaccines that had either a XBB breakthrough infection or an XBB reinfection after BA.5 or BF.7 breakthrough infection.

Of course boosted serum didn’t fare much better against any of the other omicron subvariants at the time including XBB1.5 it was formulated to combat unless there was prior infection history.

Another study, published in the Lancet, that collected h blood samples from participants that had received the most recent XBB1.5 monovalent dividing them into cohorts without prior SARS-2 infections (n = 9) and those with a prior XBB sub-variant infection prior to the booster (n = 10) found that some individuals in the former cohort had no anti-viral activity against: XBB.1.5 (n=2), XBB.1.16 (n=1), XBB.2.3 (n=3), EG.5.1 (n=3), HK.3 (n=3), and BA.2.86 (n=2) 20–29 days after their booster dose.

A combined cell culture and serological French study (n = 75), published in Nature, found that 3 monovalent doses (primary series + first booster) was completely worthless against JN1 and the dominate variant from the prior year (XBB1.5) with no detectable neutralization activity against the recent XBB-derived or BA.2.86 variants. The 2022 Bivalent booster triggered a moderate and brief neutralizing antibody titer levels against XBB and BA2.86 derived variants with barely detectable neutralization activity after 6 months while XBB infections triggered a broader cross-neutralizing response than bivalent boosters and reduced antibody titer level differences between subvariants XBB.1, EG.5.1 and BA.2.86.1. The study also uncovered evidence of probable immune imprinting from repeated boosters finding that the bivalent produced the highest antibody titer levels against the ancestral variant, a 6–9x lower titer level against BA1 and BA5 and 10–25x lower antibody titer levels against XBB and BA2.86 derived subvariants compared to BA1 and BA5.

And JN1 is no longer the dominant variant as of late April. It has been supplanted by the even more antigentically distant and booster evasive Flirt variants.

A group of Japanese immunologists from the University of Tokyo Institute of Medical Science found a subvariant descended from the dominant JN1 that has 3 mutations on the spike protein and one on the receptor binding domain rapidly spreading globally and constituting 20% of cases in the UK already. Using a pseudovirus assessment they found that this new subvariant KP2 is less infectious than JN1 but more resistant to XBB1.5 monovalent booster antibodies than antibodies in blood samples taken from people with prior XBB, EG5, HK3 or JN1 variant infections.

Virological Characteristics of the SARS-COV-2 KP.2 Variant

As I pointed out in a prior post you need Immunoglobulin A induced mucosal immunity to prevent infection at the actual site of infection. Circulating IgA does not enter mucosal secretions in the upper respiratory tract and neither do IgG induced in the lymphatic system. This is why this third rate vaccine, if you can even call it that, only has a time specific VE of 3 to 6 months and with the omicron sub variants of the past year it’s closer to 3 months with spike protein specific IgG antibodies having a half life of 87 days. Even the annual flu shot has a higher time specific VE (6–8 months against identical strains) than this supposed blockbuster product.