💉🧵 Why Novavax is the better COVID-19 vaccine
While we *still* wait for Novavax to roll out, since today is Sunday and pharmacies & customer support lines are closed, I’m taking a step back to a very basic concept and giving a reminder of WHY we’re all waiting for Novavax in the first place. And why nobody should be considering rushing out to get mRNA right now.
Some forget in the midst of all the panic, and some people looking at us “holdouts” from the outside may still be confused about why anyone would ever bother to wait for Novavax in the first place.
This will also be the topic of the next article that @DonEford releases, so keep an eye out for a much more in-depth and scientific analysis than this thread will offer.
You often hear Novavax discussed as a “traditional protein-based vaccine”, which makes it similar to vaccines like Influenza, Hepatitis B, Tdap, & HPV. This is true, which is a testament to Novavax’s safety profile, but it’s not an entirely accurate characterization.
While protein is traditional, Novavax also makes use of cutting-edge technology in two distinct ways when compared to other vaccines.
Technology 1: Sf9 cells from the Fall Armyworm moth.
This is what makes it possible to produce a high-quality protein vaccine targeting a respiratory virus in the first place. Many vaccines, like traditional flu shots, are “inactivated virus vaccines”. These products are made by growing the virus in eggs, and then inactivating it to include in the finished shot. In that process, adaptation becomes an issue. The virus is required to adapt to grow in the eggs, which means the finished product may contain antigen that is clinically significantly different from the antigen seen in the virus actually circulating in the real world.
Novavax uses a completely different process, where they skip the step of needing to “grow” the entire virus. Instead, they take the gene for the SARS2 spike protein, insert it into a baculovirus, which then infects Sf9 insect cells that come from the fall armyworm moth. Those cells then produce pure spike protein that is used in the finished product. This allows them to produce antigen that is much more closely matched to circulating viruses, just like mRNA, while still using the more traditional protein base.
Technology 2: Matrix-M adjuvant.
Matrix-M, which is a saponin-based adjuvant developed by Novavax, is the star of the entire show here. Saponins are natural plant compounds that form soap-like foams in water. Matrix-M specifically comes from the bark of the Quillaja saponaria tree, aka “soapbark tree.” An adjuvant is a substance oftentimes added to vaccines to enhance the immune response to the antigen, and Matrix-M is a next-gen adjuvant that is showing an amazing amount of promise. For example, it’s now being used in a childhood malaria vaccine in Africa, and providing 70% efficacy, compared to the 35% efficacy from previous vaccines! In addition to driving strong antibody responses (B cells) which is pretty much the only thing that older adjuvants do well, Matrix-M also elicits a strong cellular response and memory among T Cells. The Matrix-M mechanism of action is illustrated below.
Okay, cool, thanks to the soapbark tree and the fall armyworm moth. Nature is great! But how do these technologies play out in the real world when it comes to the COVID vaccine?
Do we have evidence of them *actually* providing us particularly noteworthy protection?
Yes! The following categories and studies are all proof of that, and are just a selected handful out of many dozens of studies that prove why Novavax is the best vaccine choice.
There are 5 main categories (in addition to the benefit of the JN.1 antigen target, which I’ve already described in the past) that illustrate why Novavax is the best choice:
1. Less waning/better infection protection
2. “Universal-like” variant coverage
3. Better mucosal protection
4. Less side effects
5. No IgG4 class switching
1/4
🔵Novavax wanes less over time, and provides meaningful protection against actual infection.
Study 1:
One-year follow-up of the immunogenicity and safety of a primary series of the NVX-CoV2373 (TAK-019) vaccine in healthy Japanese adults: Final report of a phase I/II randomized controlled trial: sciencedirect.com/science/articl…
This study found that priming series of Novavax induced persistent immune responses up to 1 year after the second dose.
Novavax performed better than the Pfizer vaccine for preventing lab-confirmed SARS-CoV-2 infection. Novavax has an aHR of 0.78 after the third dose and 0.86 after the fourth dose, meaning it was 14% to 22% better at preventing infection.
Study 3:
Effectiveness of NVX-CoV2373 and BNT162b2 COVID-19 Vaccination in South Korean Adolescents: pubmed.ncbi.nlm.nih.gov/40865116/
This is the same type of study as the previous one, except this time, it was conducted in an adolescent population. Once again, it found that Novavax performed better than the Pfizer vaccine. Novavax had an aHR of 0.57 for a priming series and 0.68 for a booster dose, meaning it was 32% to 43% better at preventing infection:
Study 4:
Characteristics and Outcomes for Recipients of NVX-CoV2373: A Real-World Retrospective Study in Germany: mdpi.com/2076-393X/12/4…
Within the 10 months after receiving Novavax, there was a 95% reduction in the amount of doctor’s visits associated with COVID-19 diagnosis.
🔵Additional Novavax doses shrink the antigenic range. This means that the breadth of protective antibodies, against additional and future variants, increases.
This study found that “Boosting with Novavax resulted in enhanced cross-reactive immunity to SARS-CoV-2 variants, a decreased gap between immune recognition of the variants and the ancestral strain, and the induction of a potentially more universal-like response against SARS-CoV-2 variants.”
🔵Novavax provides better protection in the upper respiratory tract, which is extremely important when trying to avoid infections in general, long covid, and translocation to the brain & lower respiratory tract:
Study 1:
Efficacy of mRNA-1273 and Novavax ancestral or BA.1 spike booster vaccines against SARS-CoV-2 BA.5 infection in non-human primates: pmc.ncbi.nlm.nih.gov/articles/PMC10…
Novavax blunted virus replication and showed a significant reduction in viral load in the airway early post-infection, at days 2 and 4. Conversely, the mRNA shot offered only limited protection at days 2 and 4, and took longer to “catch up”.
Study 2:
Detection of anti–SARS-CoV-2 mucosal IgA in clinical saliva samples after a dose of Novavax COVID-19 vaccine: medrxiv.org/content/10.110…
Salivary samples collected 28 days after vaccination showed a significant increase in anti-SARS-CoV-2 spike antibodies.
For this study, it’s notable Novavax actually had to develop their own test to establish a way to test for mucosal IgA, because we didn't have one before, because we never needed one, because no vaccines in the past have even came close to providing this level of mucosal immunity. Let that sink in.
2/4
