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Daniel Park Profile picture
@Daniel_E_Park
Sep 27 • 12 tweets • 5 min read • Read on X
Just out: mRNA COVID-19 vax do not establish in long-lived plasma cells; could account for faster waning vs. infection. Other mechanisms still protect durably vs. severe illness, but improving durability is important. Adjuvants (like in Novavax) may help.
nature.com/articles/s4159…
My previous thoughts on the preprint here.

h/t @atranscendedman
The paper shows that compared with influenza and tetanus vaccination, the mRNA COVID-19 vaccines were unable to imprint LLPCs. Also, serum IgG levels correlated well with bone marrow LLPC levels for flu and tetatnus, but not for SARS-CoV-2. Image
The discussion section is well-written, and contemplates whether this is unique to the mRNA platform or to the spike protein, since durable protection to other coronaviruses is also relative short-lived. I think it’s both.
The authors conclude with a call to explore different vaccination schedules, vaccine adjuvants, or delivery systems. Image
Naturally, those with experience working with vaccines know a primary purpose of adjuvants is to enhance durability. The existing Novavax COVID-19 vaccine uses a saponin adjuvant and I have hypothesized that it could be a key factor in why it may provide more durable protection.
Enhanced durability via adjuvants has been shown, among others, for Shingles (Shingrix vs. Zostavax). The adjuvanted platform lasts 7-10 years vs. non-adjuvanted Zostavax which dropped to 50% efficacy by year 2.

bmj.com/content/383/bm…
academic.oup.com/ofid/article/9…
And multiple animal models with the Novavax platform have demonstrated LLPCs in addition to blunting of upper respiratory tract viral load with the Novavax vaccine.

nature.com/articles/s4154…
science.org/doi/10.1126/sc…
Other COVID-19 vaccines in development using similar saponin-based adjuvants have also demonstrated induction of LLPCs in bone marrow. This suggests the spike protein may present challenges to B cell activation, but can be partially overcome via adjuvants.
science.org/doi/10.1126/sc…
Finally, the vaccine trials showed good durability (>75% at 6-months from Delta period in vaccine trial using original strain vaccine). And population based studies suggest good long-term durability with NVX


academic.oup.com/cid/article/79…
jamanetwork.com/journals/jaman…
mdpi.com/2076-393X/12/4…
Image
mRNA COVID-19 vaccines have played a critical role in blunting the impact of SARS-CoV-2 throughout the last 5 years. But since the virus circulates throughout the year, it is critical to 1) improve air quality and/or mask in high-exposure areas, 2) improve durability of vaccines.
On #2, human studies of NVX LLPCs & durability are needed to see if a solution already exists. Often animal models don't translate to humans, & durability studies are challenging due to pre-existing immunity, variants, etc. But early suggestions certainly warrant further studies

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More from @Daniel_E_Park

Daniel Park Profile picture
Sep 14
Vaccines likely lower transmission, in addition to reducing infection and severe illness. New study shows Novavax and Moderna significantly reduce viral load (amount of virus) in the upper respiratory tract.

academic.oup.com/jid/advance-ar…
Image
Novavax reduces viral load by 2.78 log10, while the Moderna vaccine was 2.12. The log10 scale is 10x for each step, indicating Moderna reduces viral load by just over 100x, and Novavax reduces viral load by over 600x. No significant reductions seen for others. Image
These results are in line with earlier animal models where the Novavax platform was associated with the largest decrease in viral replication in the upper respiratory tract.
science.org/doi/10.1126/sc…
Image
Read 10 tweets
Daniel Park Profile picture
Aug 28
There is a common and dangerous misconception that the JN.1 vaccines are inferior to KP.2 vaccines. In reality, JN.1 and KP.2 vaccines will both provide excellent protection, with each being slightly better in different aspects. But the experts were right to pick JN.1. Image
First, a bit of background. The FDA vaccine expert committee, consisting of 14 highly experienced and accomplished vaccine experts, supported selecting JN.1, with many suggesting it would be a safer and potentially better strain to select compared w/ KP.2.
fda.gov/advisory-commi…
Some examples –
Dr. Berger: “I think the antigenic close relationship between JN.1 and its sublineages, and the cross-reactivity [across] KP2 and KP3, really does suggest that JN.1 is the appropriate vaccine update to be making at this time”
Read 21 tweets
Daniel Park Profile picture
Aug 12
Preprint: Interesting study from Korea comparing homologous NVX (Novavax) and BNT (Pfizer) COVID vax. One of the few places where there are enough NVX doses to do this analysis. Slightly better effectiveness (16% better) with NVX after primary series

medrxiv.org/content/10.110…
Image
More interestingly (to me at least), NVX effectiveness is 35% higher than BNT comparing after the 1st homologous booster. There have been suggestions that homologous NVX boosts can uniquely improve antibody avidity, affinity maturation, & epitope spreading
nejm.org/doi/full/10.10…
Side note/reminder: the data for heterologous boosting strategies (mix-and-match) remain very compelling as well

nature.com/articles/s4154…
journalofinfection.com/article/S0163-…
Read 5 tweets
Daniel Park Profile picture
Aug 8
Excellent broad cross neutralization to variants with the upcoming JN.1 Novavax COVID vaccine, including some of the best responses to variants that are likely to be dominant this late fall and early winter
novavax.widen.net/s/zg79lxwknx/2…
Image
The latest CDC nowcast shows a rapid rise in KP3.1.1, which is the variant with best response to the NVX JN.1 vaccine. Others variants to keep an eye on include LB.1 (a direct JN.1 descendant) and LP.1 (KP1.1 descendant)
covid.cdc.gov/covid-data-tra…
Image
This follows an expected decline in KP.2 over the last few weeks, which is one reason why VRBPAC recommended not chasing this branch (KP.2 variant) but to target the trunk (JN.1).
Read 4 tweets
Daniel Park Profile picture
Apr 13
How our family stayed COVID-negative when my 2-year old was infected. An epidemiologists’ perspective. Image
In late February, our toddler woke up with a runny nose. Anyone with a toddler will know runny noses are very typical. However, thanks to ongoing local surveillance (which I monitor ~weekly), I knew case rates were slightly elevated in our area, and that led me to test. Image
Lesson 1: If you know local circulation rates, you can adjust your threshold for when mild symptoms may warrant a test.
Lesson 2: We can get tests for free from our local library. This is a great resource that should remain widely available.
Read 22 tweets
Daniel Park Profile picture
Apr 11
Small but helpful study of Novavax from Germany highlighting some of the key benefits of this vaccine option. Very low incidence of side effects among this high-risk population. And excellent long-term protection (95% at 10 months). Image
Paper: mdpi.com/2076-393X/12/4…
Of note, there is generally a much higher proportion of individuals choosing Novavax from high-risk populations, often due to adverse reactions from prior mRNA doses. Here, there were zero sick-leave days after NVX receipt, and negligible reportable side effects.
Read 4 tweets

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