22 June 2023 Episode 336 Preparing for a new XBB specific COVID vaccine.

Episode 336: Preparing for a new XBB specific COVID vaccine.

Dear colleagues,

Based on recent interactions with Patrick Smits, Pierre Vandamme and others, I could prepare the present follow-up episode on the state of the epidemic, the most recent data on (waning) vaccine effectiveness  and the prospect for a new vaccine for the autumn.

See  

Par 1 Epidemiological situation

We are definitely in a quiet period.  According to both global figures from WHO (Ep 336-1), from US (Ep 336-2) and from Belgium (Ep 336-3), the numbers of COVID hospitalizations and deaths are still decreasing.

Sciensano 22 June 2023

Both globally, in US and in Belgium, the descendants of the BJ.1/BA.2.75 recombinant XBB remain predominant

Belgium

Par 2 Data on vaccine effectiveness (VE)

As everybody knows, VE against infection and transmission has progressively and dramatically decreased during the subsequent omicron waves, but what about effectiveness against severe outcomes (hospitalization and death), especially in the older population?

Mortality in 65+ US adults, who received a BA5 bivalent booster within 6 months as compared with unvaccinated individuals is still much lower (Ep 336-4)

Data from UK Health Security comparing older adults  who received either 2, 3 or 4 vaccines (the latter being bivalent) over time provides a more nuanced picture (Ep 336-5)

• The VE of the bivalent booster wanes in 50+ adults over 6 months from about 50 % to 20 %

• VE against mortality in 65+ adults also wanes, but remains much higher (over 60% after 6 months)

• As could be expected, VE is particularly low against the XBB.1.5 variant

Ep 336-6: VRBPAC (Vaccines and Related Biological Products Advisory Committee) : Evaluation of VE of bivalent versus monovalent vaccines 15 June 2023

Par 3: New XBB.1.5 vaccine

Ep 336-7: Presentation by MODERNA to promote their novel monovalent XBB.1.5 specific vaccine

The cross-neutralization between BA.5 and XBB is very limited → these variants are antigenically very different

Indeed many differences between BA.5 and XBB subvariants

Rather limited differences between XBB subvariants → cross-neutralization very likely.

Favorable cross-neutralization by both XBB.1.5 and XBB.1.16 monovalent vaccines in mice!

Also favorable neutralization titers in humans after XBB.1.5 booster

Note: Pfizer (Novavax, Chinese companies…) are certainly also working on XBB vaccines, but I could not find any data on those.

Par 4: Recommendations for the next season

Ep 336-8, -9 and -10:  Common conclusions from WHO, VRBPAC and EMA

The reason to prefer XBB monovalent versus bivalent vaccines (including Wuhan Spike) is IMPRINTING

Ep 336-11:  Advice of Belgian Superior Health Council of 22 June on timing, target groups and co-administration of COVID with Flu vaccine for winter 2023-2024

But first a nice graph on relative mortality risk from COVID by age and co-morbidity (based on US data over the entire epidemic):

TIMING of COVID and FLU vaccine

TARGET GROUPS:

ADULTS

Others in this group of adults:

• Body mass index > 40
• At least one co-morbidity (even if stabilized): pulmonary, renal, hepatic, cardiac, metabolic, neurological
• Under immune suppression; because of immune deficiency, cancer, transplant, renal dialysis

CHILDREN

SOME CONCLUSIONS

• The Omicron epidemic continues to generate new XBB subvariants, they are evasive towards immunity induced by BA.4/5 (infection or vaccination), but they are rather antigenically similar amongst each other.
• Vaccine effectiveness, after bivalent booster, is weak against infection, it wanes against hospitalization, but remains substantial against mortality.
• Bivalent vaccines come with imprinting:  the Wuhan strain mainly stimulates irrelevant responses (against “escaped” epitopes) and may weaken the induction of more relevant responses against new epitopes. 
• This imprinting phenomenon is mainly documented at the level of antibodies, which may explain the very weak protection against infection by bivalent boosters.  The still substantial protection against severe disease may rely on T cell responses against more conserved epitopes.
• There is preliminary mouse and human data that monovalent XBB vaccines induce substantial levels of specific neutralizing antibodies in vitro, but there are no data on clinical protection yet.
• WHO, FDA and EMA recommend the use of monovalent XBB1.5 vaccine to boost immunity in at risk subjects.  The Belgian Superior Health Council has specified the main target groups: high risk patients, but also advises to vaccinate professional and cocoon care givers.   

Best wishes,

Guido