#18,115
Regardless what H5Nx does in the months ahead, the SARS-COV-2 virus continues to circulate globally, producing new waves of infection as it evolves into new sub-variants (see above).
While few countries still report hospitalizations or deaths from COVID, studies show the virus continues to exact a significant toll on public health around the world.
Add in increased chronic health problems linked to `Long' or `Post' COVID syndrome (see CIDRAP Study reveals persistent risk of death, symptoms in COVID survivors at 3 years), and there are ample reasons to continue to follow its evolution and spread.
Unfortunately, COVID evolves so quickly, it is impossible to know what variant will be dominant 3 or 6 months from now. Few variants have remained `on top' for longer than 6 months, and many have come and gone in half that time.
Given the lead-time it takes to develop, produce, and distribute vaccines, this has made it difficult to select a target strain for each updated vaccine. Last week the FDA announced their intention to recommend the JN.1 strain (see below) for next fall's vaccine.
Updated COVID-19 Vaccines for Use in the United States Beginning in Fall 2024
FDA's Vaccines and Related Biological Products Advisory Committee (VRBPAC) met on June 5, 2024, to discuss and make recommendations on the selection of the 2024-2025 Formula for COVID-19 vaccines for use in the United States beginning in the fall of 2024.
The committee unanimously voted to recommend a monovalent JN.1-lineage vaccine composition. Following the vote, the committee discussed considerations for the selection of a specific JN.1 lineage SARS-CoV-2 strain (e.g., JN.1 or KP.2) and expressed a strong preference for JN.1.
(Continue . . . )
The problem being, that in recent weeks the JN.1 strain has been rapidly usurped by several of its offspring (KP.3, KP.2, and LB.1). Some have recommended going with the newer KP.2 variant instead, but there are no guarantees that will be the dominant strain 5 months from now.
Be glad it isn't your decision to make.
While we wait to see how this all plays out, we've a new preprint from the Kei Seto Lab at the University of Tokyo, on this new crop of COVID contenders (KP2.3 & LB.1 appear most problematic).
Although a lot of what follows is fairly technical, the bottom line is pretty simple. SARS-CoV-2 doesn't appear anywhere near going quietly into the night.
Follow the link to read the full report. I'll have a postscript after the break.
Abstract
The SARS-CoV-2 JN.1 variant (BA.2.86.1.1), arising from BA.2.86.1 with a substitution in the spike (S) protein, S:L455S, exhibited increased fitness and outcompeted the previously predominant XBB lineages by the beginning of 2024.
Subsequently, JN.1 subvariants including KP.2 (JN.1.11.1.2) and KP.3 (JN.1.11.1.3), which convergently acquired S protein substitutions such as S:R346T, S:F456L, and S:Q493E, have emerged concurrently.
Furthermore, JN.1 subvariants such as LB.1 (JN.1.9.2.1) and KP.2.3 (JN.1.11.1.2.3), which convergently acquired S:S31del in addition to the above substitutions, have emerged and spread as of June 2024.
We have recently reported the virological features of KP.2. Here we investigated the virological properties of KP.3, LB.1, and KP.2.3. We estimated the relative effective reproduction number (Re) of KP.3, LB.1, and KP.2.3 using a Bayesian multinomial logistic model based on the genome surveillance data from Canada, the UK, and the USA, where these variants have spread from March to April 2024.
The Re of KP.3 is more than 1.2-fold higher than that of JN.1 and higher than or comparable to that of KP.2 in these countries. Importantly, the Re values of LB.1 and KP.2.3 are even higher than those of KP.2 and KP.3.
These results suggest that the three variants we investigated herein, particularly LB.1, and KP.2.3, will become major circulating variants worldwide in addition to KP.2 and KP.3.
We then performed virological and immunological experiments with pseudoviruses. The pseudovirus infectivity of KP.2 and KP.3 was significantly lower than that of JN.1. On the other hand, the pseudovirus infectivity of LB.1 and KP.2.3 was comparable to that of JN.1.
Neutralization assay was conducted by using four types of breakthrough infection (BTI) sera with XBB.1.5, EG.5, HK.3 and JN.1 infections as well as monovalent XBB.1.5 vaccine sera. In all four groups of BTI sera tested, the 50% neutralization titers (NT50) against LB.1 and KP.2.3 were significantly lower than those against JN.1 (2.2-3.3-fold and 2.0-2.9-fold) and even lower than those against KP.2 (1.6-1.9-fold and 1.4-1.7 fold). Although KP.3 exhibited neutralization resistance against all BTI sera tested than JN.1 (1.6-2.2-fold) with statistical significance, there were no significant differences between KP.3 and KP.2.
In the case of infection-naive XBB.1.5 vaccine sera, the NT50 values of JN.1 subvariants were very low. In the case of XBB.1.5 vaccine sera after natural XBB infection, the NT50 values against KP.3, LB.1 and KP.2.3 were significantly lower than those of JN.1 (2.1-2.8-fold) and even lower than KP.2 after infection (1.4-2.0-fold).
Overall, our results suggest that the S substitutions convergently acquired in the JN.1 subvariants contribute to immune evasion, and therefore, increase their Re when compared to parental JN.1. More importantly, LB.1 and KP.2.3 exhibited higher pseudovirus infectivity and more robust immune resistance than KP.2. These data suggest that S:S31del is critical to exhibit increased infectivity, increased immune evasion, and therefore, potentially contributes to increased Re.
Five weeks ago, it appeared as if KP.2 was the heir apparent, but now it looks as if KP.3 or LB.1 have some distinct fitness advantages. Of course, by October, we could be dealing with an entirely new group of up-and-coming variants.
- The good news is, we haven't seen any signs that these emerging variants produce more severe illness, or increased deaths.
- The bad news is, global testing, surveillance, and reporting on COVID have been largely dismantled, making it less likely to pick up any early warning signs of increased virulence.
