"The Rise of KP.3.1.1: Enhanced Infectivity and Implications for Vaccine Effectiveness"

As we approach August of 2024, it's crucial to reflect on the rapid evolution of the COVID-19 virus and its variants since the World Health Organization initially recommended vaccines targeting JN.1, such as Novavax's approach, to the CDC-approved KP.2 target, and now beyond KP.3 to KP.3.1.1,.with more in the line up behind that.

This progression has led to the emergence of the KP.3.1.1 (JN.1.11.1.3.1.1) variant, a strain further challenging vaccine efficacy. KP.3, could evade the JN.1 and KP.2 immune response, and now the KP.3.1.1 variant is showing greater ACE-2 binding and greater immune evasion and suppression than KP.3

"KP.2 shows the most significant resistance to the sera of monovalent XBB.1.5 vaccinee without infection (3.1-fold) as well as those who with infection (1.8-fold). Altogether, these results suggest that the increased immune resistance ability of KP.2 partially contributes to the higher Re more than previous variants including JN.1." (1)

KP.3 variant further eroded the immune response to XBB.1.5. , JN.1 and KP.2. In a new study, "Virological characteristics of the SARS-CoV-2 KP.3.1.1 variant" KP.3.1.1 takes that even further than KP.3.

The KP.3.1.1 variant of COVID-19 has a much higher ability to infect cells than the KP.3 variant. Researchers tested how well different sera (blood samples) could neutralize KP.3.1.1.

They used sera from people who had breakthrough infections (BTI) with the XBB.1.5 or EG.5 variants, sera from people who had infections with the HK.3 or JN.1 variant, and sera from people vaccinated with the monovalent XBB.1.5 vaccine.

The results showed that the sera's ability to neutralize KP.3.1.1 was significantly lower compared to KP.3. Specifically, the 50% neutralization titer (NT50), which measures how well the sera can neutralize the virus, was 1.4-1.6 times lower for KP.3.1.1 in all groups. For those vaccinated with XBB.1.5, the NT50 was 1.3 times lower against KP.3.1.1 compared to KP.3. This means that KP.3.1.1 can more effectively evade the immune response than KP.3.

Overall, KP.3.1.1 not only infects more efficiently but also evades neutralization better than KP.3. This aligns with findings that JN.1 subvariants with the S:S31 del, like KP.2.3 and LB.1, show enhanced infectivity and immune evasion compared to other JN.1 subvariants without the S31 deletion (examples, JN.1, KP.2, KP.3) highlighting the evolutionary significance of S:S31del in the JN.1 lineages.

In summary, the XBB.1.5 vaccine is less effective against the KP.3.1.1 variant, meaning that while it still offers some protection, its ability to neutralize the virus is significantly reduced.

We already have KP.3.1.1.1 and KP.3.3.1 with even higher growth advantages following KP.3.1.1, which we will discuss in another update. How much further will the virus have evolved by October or November when the JN.1 and KP.2 targeted vaccines become available? Given the current level of mitigation efforts, nearly everyone will have already been infected with a KP.3 sub-variant.

This is all pointing to the fact that without mitigation, the virus is evolving at an increasing rate of speed. Very dangerously, most people are exposed to more evolved versions of the virus than the vaccines target before the vaccines come out. We know that since the virus evades the antibodies to the vaccines, then it can still infect people, keep spreading and it can still lead to Long COVID.

If you are someone who manages to avoid exposure for 7 to 10 months, then the vaccines will likely offer the benefit of boosting the memory T-cells, helping to prevent severe disease and death, and they likely provide a shorter 2 to 3-month boost of antibodies and spike specific T-cells that may partially help reduce the impact of an acute infection.

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Sources:
1. "Virological characteristics of the SARS-CoV-2 KP.2 variant"
(May 20, 2024)

https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(24)00298-6/fulltext

2. "Virological characteristics of the SARS-CoV-2 KP.3.1.1 variant" July 17, 2024
https://www.biorxiv.org/content/10.1101/2024.07.16.603835v1

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For more info on the history of evolution towards immune evasion and suppression of SARS-CoV-2 check this out.

“The History of COVID-19 Immune Evasion and the Increasing Pace of Evolution”
”You'll encounter excerpts from the referenced study followed by simplified explanations aimed at making the information accessible to a broader audience, including high school students. This effort aims to enhance understanding of the gravity of the situation and underscore the importance of taking decisive action against the virus.”

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Another post from 2023 goes into more detail on the timing of boosters and the potential for an autoimmune response.

“Why timing and avoiding infection is important.” (Updated 9/24/2023)

https://tactnowinfo.substack.com/p/are-you-considering-taking-an-updated

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