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Daniel Park Profile picture
@Daniel_E_Park
Mar 8 • 6 tweets • 3 min read • Read on X
Preprint: Immunity from mRNA vaccines wanes more rapidly due to inability to induce long lived plasma cells in bone marrow. This seems unique to current mRNA, and less for the adenovirus vector (J&J, AZ) and protein-based (Novavax) options

medrxiv.org/content/10.110…
Image
H/t to @ENirenberg who has an excellent thread on this
To be clear, mRNA vaccines have been revolutionary and critical in blunting the pandemic. But their main "problem" is rapid waning (loss of protection). This includes both SARS-CoV-2 vaccines and so far, RSV mRNA vaccines.
.reuters.com/business/healt…
Typical vaccines are usually protective for years or decades. However, many studies show that mRNA COVID-19 vaccines lose protection quickly after 4-6 months. In contrast, AZ and Novavax seem to protect for at least a year.

jamanetwork.com/journals/jaman…

Image
This has not been as critical since more frequent boosting has been necessitated by the rapid mutations in SARS-CoV-2. However as the virus stabilizes in human circulation, it becomes increasingly important to address, either through mRNA platform mods or heterologous boosting
Heterologous (mix-and-match) boosting has long been shown to improve durability of protection, and is a good, immediately available approach that is vastly underutilized

Refs:


jamanetwork.com/journals/jaman…
journalofinfection.com/article/S0163-…
journalofinfection.com/article/S0163-…

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More from @Daniel_E_Park

Daniel Park Profile picture
Mar 1
Interesting: different immune responses to Novavax & mRNA COVID vaccines. TLDR: NVX has higher proportion of the "best" IgGs (IgG3), while mRNA have higher of the "not always good" IgG4. IMO more importantly, NVX has stronger Fc-effector functions
journalofinfection.com/article/S0163-…
Fc-effector functions have been hypothesized to be behind much of the efficacy w/ NVX. Ppl with essentially undetectable IgG still had >60% efficacy vs infection in the original trials.
nature.com/articles/s4146…
Side note, I think Dr. Lin is right on this one as well:
Read 10 tweets
Daniel Park Profile picture
Feb 26
Just released: Pretty remarkable 1-year durability data for Novavax 2-dose primary series. Though there is some expected waning, there was >65% efficacy at 1y (mRNA options typically wane to this level by ~4-5 months). Also fewer waning differences by age.
sciencedirect.com/science/articl…
Image
Refs:
NVX:
BNT:
Waning:
sciencedirect.com/science/articl…
sciencedirect.com/science/articl…
thelancet.com/journals/lanre…
To illustrate age stratified data, I took NVX data from the Japan paper and compared w/ a BNT paper from Norway. For BNT, nAbs & IgG largely back to baseline levels in older individuals by 5m, but remain at protective level at 1y w/ NVX, and more similar to young ages throughout. Image
Read 4 tweets
Daniel Park Profile picture
Jan 11
Preprint: saponin adjuvants (like the one in Novavax) shown to enhance durability (length) of protection compared with mRNA options. Potentially relevant as we shift to annual doses for COVID-19.
biorxiv.org/content/10.110…
Image
Per the authors, "in a murine vaccine study, the adjuvants greatly improved the potency, durability, breadth, and neutralization of both COVID-19 and HIV vaccine candidates, suggesting the potential broad application of these adjuvant constructs to a range of different antigens." Image
Earlier studies have looked at this directly for Novavax v. mRNA as well, which included improved blunting of replication in the upper respiratory tract with NVX. This could have implications for reduced transmission.
science.org/doi/10.1126/sc…
Read 5 tweets
Daniel Park Profile picture
Dec 8, 2023
Important study in Nature may have some implications for reactogenicity and/or efficacy of mRNA vaccines. The pseudouridine can cause a frameshift (e.g. mistranslation) when the body converts mRNA to proteins
nature.com/articles/s4158…
First to clarify what a frameshift is (skip ahead if biologically inclined): The ribosome is the thing in your cells that "reads" the mRNA and produces the resulting protein. The ribosome reads mRNA nucleotides ("letters") in sets of three. Like acg uug aga cca
It turns out the pseudouridine can be hard for ribosomes to read, and it can lead to them "slipping" or skipping a letter. So the prior acg uug aga could instead be read acg uga gac... the resulting protein would be almost entirely incorrect after the frameshift
Read 9 tweets
Daniel Park Profile picture
Oct 3, 2023
Finally, the FDA has authorized the Novavax XBB booster, without restrictions. The NVX het. boost option is 1) up to 9x more effective at preventing infections, 2) has fewer side effects, 3) provides durable, broad protection vs new variants

fda.gov/vaccines-blood…
Refs:
1)
2)




3)
journalofinfection.com/article/S0163-…
tandfonline.com/doi/full/10.10…
thelancet.com/journals/lance…
sciencedirect.com/science/articl…
cdc.gov/mmwr/volumes/7…
medrxiv.org/content/10.110…
biorxiv.org/content/10.110…
sciencedirect.com/science/articl…
There have also been studies suggesting the Novavax vaccine may be uniquely effective are reducing upper respiratory tract carriage (and therefore likely to reduce transmission):

science.org/doi/10.1126/sc…
nature.com/articles/s4146…
Read 4 tweets
Daniel Park Profile picture
Sep 19, 2023
Many EU agencies are excited about the updated Novavax vaccine. Germany just confirmed purchase of 10.6 million doses for this fall, 3 million in Italy. Europe has run large RCTs comparing vaccines showing benefits of heterologous boosting with AZ and NVX
corriere.it/politica/23_se…
These RCTs have shown tremendous benefits with heterologous boosting not only with immunologic endpoints, but more importantly with durability and protection from breakthrough infections (~9x better protection vs. homologous mRNA)

nejm.org/doi/full/10.10…
journalofinfection.com/article/S0163-…
Adding on the lower reactogenicity (side effects) of the Novavax platform, the cost-benefit advantages of NVX helps explain the growing international interest in the product.
x.com/Daniel_E_Park/…
Read 5 tweets

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