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. 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…

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…
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…

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…
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…

How our family stayed COVID-negative when my 2-year old was infected. An epidemiologists’ perspective. 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.

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). Paper: mdpi.com/2076-393X/12/4…

Further evidence that COVID-19 vaccination protects you from poor cardiovascular outcomes, this time from a cohort of over 20 million people. Vaccinated individuals had at least half the risk of adverse outcomes w/in 30 days post-infection.

heart.bmj.com/content/early/…
h/t @EricTopol

https://x.com/EricTopol/status/1767692589506167131?s=20

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…
H/t to @ENirenberg who has an excellent thread on this

https://twitter.com/ENirenberg/status/1765957382176223526?t=mQnHR4sNI4cG03qZr1fGZw&s=19

Yikes! Microplastics and nano plastics frequently found in carotid artery plaques (58%), and were associated with much higher risk of heart attack, stroke, and death (4.5x higher risk)
nejm.org/doi/full/10.10… The researchers saw jagged edged microplastics embedded in the plaque (possibly serving as an anchoring point for plaque growth)

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…

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…
Refs:
NVX:
BNT:
Waning:
sciencedirect.com/science/articl…
sciencedirect.com/science/articl…
thelancet.com/journals/lanre…

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…
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."

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

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…

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-…

Recently released immunogenicity results from a Phase 3 RCT of the original Novavax vaccine when used as a booster. Good safety profile and excellent immune responses regardless of prior vaccine platform, even against Omicron BA.1 and BA.5
sciencedirect.com/science/articl… Immune responses suggest booster shots provide protection that exceed the 87% efficacy based on correlates of protection established in a previous study
nature.com/articles/s4146…

Helpful results to inform the strategy behind annual COVID-19 vaccines. Good durability and efficacy (>80%) against hospitalization over 10 months with AstraZeneca (ChAdOx1).

https://t.co/9hFKVLiEBosciencedirect.com/science/articl…
Comparatively, mRNA efficacy vs hospitalization wanes ~50%-80% by the fourth month after vaccination:

https://t.co/hntIoJhpbx
And significant waning vs. infection:
https://t.co/w6bsK0lSIibmj.com/content/379/bm…
cdc.gov/mmwr/volumes/7…
nature.com/articles/s4146…

RCT of Covovax / Novavax COVID vaccine in children 2-11y and 12-17y. Excellent immune responses across variants that had higher titers than adults. Also very low rate of side effects, with no myocarditis reported.
jamanetwork.com/journals/jamap… This figure shows excellent antibody responses in both adolescents and children through at least 6 months. Many vaccine platforms have differential responses by age, but the adjuvant (Matrix-M) may be helping responses across the age spectrum.

This WaPo article serves as a reminder that having multiple vax platforms is important. mRNA vaccines are great, but newer doesn't necessarily equal better. Cuba achieved broad coverage and strong protection with a protein vaccine (similar tech to Novavax)
washingtonpost.com/opinions/2023/… Although the vaccine took a bit longer to develop, by the end of Sep 2021, they achieved >80% coverage. A remarkable achievement.

Important study of Novavax (ancestral & BA.1) and Moderna boosters in primates. All have effective long-term immune responses and lower viral replication, but only NVX had significantly lower viral loads in upper airways, which could limit transmission. science.org/doi/10.1126/sc… Panel E shows some of the mRNA-1273 boosted NHPs with similar upper airway viral loads to controls, whereas the viral loads are much lower (or non-detectable) after Novavax boost, with significance shown using AUCs in panel F.

Preprint of NVX-CoV2373 immunogenicity outcomes by age and HIV status. Very high seroconversion rates (i.e. protection) in all groups (98.3% for younger and 94.3% for older adults), regardless of age and HIV status.
medrxiv.org/content/10.110… This is important in context of immunosenescence and higher risk of severe disease in older adults, which is well characterized for all vaccines, including mRNA.

ncbi.nlm.nih.gov/pmc/articles/P…
nature.com/articles/s4358…

I’ve been asked for a list of Novavax studies. Apologies for the long thread but compiling some selected studies into a narrative here, hope this is helpful:
1) Original RCT shows >99% efficacy against severe disease and >90% vs. infection: nejm.org/doi/full/10.10… 2) Nvx generates a broad immune response (likely thanks to the adjuvant): jci.org/articles/view/…
(Side note: The adjuvant also provides great immunologic properties for their flu vax and the malaria vax which is being rolled out)
thelancet.com/journals/lanin…
thelancet.com/journals/lanin…