VRBPAC: June 5, 2024
Contact: Thepeoplesstrategist@gmail.com
Organizing for a Better Tomorrow
Overview
2024 strain selection is seeing additional challenges from previous years.
This has major implications for public health.
Antigenic Shift and Vaccine Strategy
Addressing the objective of this VRBPAC meeting,
“Selection of strain(s) to be included in the 2024-2025 Formula for COVID-19 vaccines”
BA.2.86: A watershed moment that changed everything
BA.2.86 was antigenically further from wild-type SARS-CoV-2 than wild-type SARS-CoV-2 was from SARS-CoV-1.
BA.2.86 and its lineages have become dominant and replaced most others.
It’s a challenging time to predict the next dominant variants
Variants under discussion:
SARS-CoV-2 has a faster and less predictable rate of mutation than influenza…
Leaving too many options to choose from.
Fighting the Variants We Can’t See
The problem facing us is the speed at which these variants evolved.
No matter what vaccine gets picked now, by the time production timelines are met we will be inevitably facing multiple new variants.
*Colors are NOT consistent between variants*
JN.1.11 sub-lineages such as KP.2/KP.3 have continued to evade other variants and each other.
Choosing too specific of a variant could leave us with ineffective vaccines, reminiscent of bivalent vaccines.
All emerging JN.1 sub-variants favor immune evasion above infectivity and it’s very consistent.
Comparative Immune Evasion in Variants
KP.2 is known as FLiRT, and KP.3 is known as FLuQE to represent amino acid changes.
KP.2 is also called JN.1.11.1.2 and JN.1 + R346T + F456L.
Immune Imprinting
SARS-CoV-2, a syncytial coronavirus, is running rampant and we can’t ignore it.
This creates a complex immune landscape forcing regulatory decisions to contend with the effects of multiple infections and vaccinations.
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To overcome imprinting, at least two exposures to a new antigen are needed.
Consequently, imprinting is no longer something on the horizon; it’s something we need to deal with right now.
Theoretically, infection qualifies as an antigen exposure but high variability in variants makes it unclear which variant infected a person.
It’s also unethical to rely on infection–based immunity even for immunocompetent individuals when it frequently results in long-term consequences.
At least two vaccine doses should be made available each time a new strain is recommended.
Overcoming Antigenic Shift
Two exposures to an antigen are required after large shifts in viral mutation (i.e., BA.2.86). We can’t depend on infection-based immunity when each variant has immune evasion to previous ones and simultaneously opening the door to long term consequences.
That means regardless of either the mRNA or protein-based vaccine platform being used, both platforms require two antigen exposures to protect people.
It’s important to recognize that we see this with both influenza & SARS-CoV-2, so this is a property of our immune system that a mutating virus is exasperating.
And we need to acknowledge that the stakes are much higher with COVID than influenza.
The WHO antigenic cartography shows the history of the pandemic in a single chart.
It demonstrates the relative distance from most major variants as well as SARS-CoV-1.
This is the consistent hurdle to overcome.
The chart on the far left demonstrates Novavax’s ability to close the antigenic gap between wild-type, BA.1, & BA.5.
The relative antigenic distance between variants is represented in the charts below.
Below we can compare the relative antigenic distance between JN.1 and its emerging subvariants, demonstrating that sufficient neutralization responses are within reach.
The range of mutational shifts are within Matrix-M’s ability to shrink antigenic range
Even when the latest variants are not targeted directly, subsequent doses of Novavax reduce the gap between targeted antigen and later variants creating an increased neutralization response.
But can we extrapolate this to our current variant landscape?
WHO: “The trajectory of further SARS-CoV-2 evolution indicates that JN.1 will likely be the progenitor of SARS-CoV-2 variants, in the near term.”
JN.1 will have more in common with its sub-variants than they will have with each other, making it an ideal variant selection in a challenging landscape.
The Case for Targeting JN.1
JN.1 exposure demonstrates a neutralizing response against emerging variants.
KP.2 & 3 are dominating globally but KP.2 is declining & the prediction that KP.3 will be the next dominant variant in the US is not significantly represented in the current data.
The Case Against Targeting KP.2/KP.3
Limitations:
KP.3 Prediction
JN.1.16.1 Reality
The problem is those variants evolved in less than two months and we are likely to see new immune evasive variants before an August rollout.
The development of Novavax was funded by operation warp speed.
Americans should have access to the protection they funded.
Right now, pharmacists are allowed to administer an additional Novavax dose within two months to immunocompromised people. The immunocompetent population should also have access to additional doses.
This is about the vaccine platform, not the antigen
The Novavax vaccine has the potential to create consistent protection without gaps… but once a year won’t cut it.
Americans need consistent access to match the consistent protection.
Unfortunately, this regulation has created confusion with pharmacists, denying access and leaving people unprotected.
Novavax’s Optimal Timing for Consistent Peak Protection
If it’s not the two month protocol then no one should be getting any COVID vaccine more often than every six months.��
IgG4 is a factor that needs consideration
But at the last ACIP, the CDC changed their official language to every 4 months, putting our highest risk population in potentially greater danger.
All American COVID vaccines affect IgG4.
Each platform handles this effect differently
In the best situation, six months is needed to reset this effect.
This needs to be considered for the timing of ANY vaccines.
Pediatric Novavax Approval
Parents have lost faith in pediatric COVID vaccines but not vaccination in general.
We’ve had data showing it’s safe & effective since 2022.
Long COVID in kids is a major concern & we need more tools.
We need a new pediatric COVID vaccine.
The evidence shows that JN.1 makes the most sense for targeting in the 2024-2025 vaccination season. Selecting this variant would help prepare the vaccinated population to combat sub-lineages emerging from JN.1 such as KP variants and others that have not yet been observed.
If the decision is made to recommend a KP or later variant for mRNA, it should not prevent Novavax from offering a JN.1 product.
Conclusion