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Novavax vs mRNA vaccine

This thread explains how is different from the and and describes some of the benefits such as broadened recognition, more durable , and fewer side effects. 🧵 1/

The one page easier to share version of this thread can be found at: threadreaderapp.com/thread/170

Novavax is a protein based vaccine, where similar designs have also been used for many years for tetanus, diphtheria and hepatitis B. Novavax presents the full COVID-19 Spike protein into nanoparticles designed to mimic the structure of the virus itself ( novavax.com/science-technology ). 2/

mRNA vaccines on the other hand get your immune cells to produce copies of the full Spike protein as single Spikes on their own which may interact differently with the immune system than Novavax's multi-Spike arrangement around a core. This video shows you how the mRNA Spikes are produced in your body ( youtube.com/watch?v=8nD6Q9X0SF ). 3/

Another big difference between Novavax and the mRNA vaccines is that Novavax uses an adjuvant called Matrix-M made from the soapbark tree to enhance the immune response to the vaccine. This adjuvant induces early activation of innate immune cells at the injection site and in the draining lymph nodes ( tandfonline.com/doi/full/10.10 ). H/T: @paulseaman31 4/

You can read the study to to get much more details about the mechanisms of action with Matrix-M, including interesting facts such as within 24 hours both the Spike antigens and adjuvant are undetectable at the injection site since they have already been processed and transported to the draining lymph nodes by immune cells.

I wonder if that is one of the reasons why many people feel much less pain in their arms after injection compared to mRNA shots? 5/

Using Matrix-M translates into an improved magnitude and quality of the antibody response to the Spike protein (antigen) and importantly broadened recognition of locations on the Spike (epitopes). 6/

This was actually seen in the real world with the BA.1 and BA.5 variants and the original Novavax vaccine formula. Both Pfizer and Moderna released bivalent BA.1/BA.5 vaccines in fall 2022 since the antibodies generated from their original mRNA vaccines could no longer neutralize these newer Omicron variants. 7/

Novavax however did not release a bivalent vaccine because their original vaccine formula with Matrix-M still worked with the BA.1 and BA.5 variants. The Matrix-M adjuvant elicited antibodies from a broader set of locations on the Spike protein (epitopes) so even when some of the locations mutated with BA.1 and BA.5, the conserved locations could still be recognized by the immune system. ( medrxiv.org/content/10.1101/20 ). 8/

Many people have anecdotally discovered and reported that Novavax doses had much lower side effects than when they received an mRNA shot. Multiple studies have now shown this to be the case as well. One preprint study (supported by Novavax) that compares the reactogenicity (frequency of side effects) of Novavax and mRNA vaccines ( medrxiv.org/content/10.1101/20 ). H/T: @michaelzlin 10/

medRxiv · Protein Vaccine Demonstrates Less Reactogenicity than mRNA – A Real World StudyA prospective, observational study investigated the burden and impact of vaccine reactogenicity in adults from the United States and Canada who received an approved/authorized mRNA COVID-19 vaccine or the Novavax COVID vaccine as a booster dose. As part of the real-world study, reactogenic events captured via patient symptom diaries were compared. Results demonstrated that the overall percentage of Novavax COVID booster recipients experiencing any reactogenicity event (77.6%) was lower than that of mRNA doses (95.9%). ### Competing Interest Statement MR and AMM are employees and shareholders of Novavax Inc. ### Funding Statement This work was supported by Novavax, Inc. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Advarra institutional review board gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Requests for data will be considered.

They found a notable difference in the percentage of reported side effect symptoms with Novavax being lower in each category:
* 30.8% lower muscle pain
* 30.4% lower injection site pain
* 25.7% lower fatigue
* 25.4% lower injection site tenderness
* 24.9% lower malaise
* 22.4% lower swelling
* 18.3% lower headache
* 17.5% lower joint pain
* 13% lower redness
* 12% lower fever
* 3.5% lower nausea/vomiting

11/

Jeff Gilchrist

What about people who had mRNA doses previously but want to consider Novavax?

There have been several studies now that found mixing the two, getting mRNA and then Novavax actually gave better results than just mRNA on its own. 12/

One study found that getting Novavax as a booster after mRNA "may enhance the persistence and durability of vaccine-mediated immunity compared to mRNA options" with slower decay rate compared to an mRNA booster dose and less side effects than mRNA boosters ( tandfonline.com/doi/full/10.10 ). H/T: @daniel_e_park 13/

A randomized controlled trial found that getting a Novavax dose after Pfizer mRNA elicited the highest humoral and peak cellular immune responses ( journalofinfection.com/article ). H/T: @michaelzlin 14/

Neutralising antibodies against Omicron BA.1 and BA.2 were higher with Novavax after mRNA compared to two mRNA doses. The mRNA + Novavax combination also had the lowest rate of breakthrough infections and the study also found fewer moderate and severe systemic adverse effects for Novavax than Pfizer mRNA. 15/

Now you have more details as to how Novavax is different and some of the nice benefits including for people who had mRNA shots previously. I'm hoping that the Matrix-M adjuvant will again show its ability to broaden the immune system's ability to choose epitopes so that it might continue to work better for upcoming variants as it did when BA.1 and BA.5 emerged. 16/

FYI, I do not work for Novavax or have any investments or make any money from Novavax selling products. I am a little confused as to why Novavax just recently filed their regulatory approval paperwork with Health Canada as many people are waiting for the fall boosters so it would be a shame if they were not available soon like the mRNA fall boosters are expected to be. 17/

While vaccines are important, they should be the last layer of protection to rely on in case all the other layers fail and you end up getting exposed to a pathogen. Vaccines should not be the one and only layer governments all seem to be currently relying on. 18/

ASHRAE Standard 241, Control of Infectious Aerosols ( ashrae.org/technical-resources ) was released in July 2023 so this should now be adopted and required by governments in air quality standards for buildings like they already require clean drinking water standards for these same buildings. 19/

www.ashrae.orgASHRAE Standard 241, Control of Infectious Aerosols | ashrae.orgLearn more about ASHRAE Standard 241, Control of Infectious Aerosols at ashrae.org

It is important to have good indoor air quality, not just from viruses but also for cognitive function and from other air pollutants (like wildfire smoke) which have been linked to various health problems ( mstdn.science/@jeffgilchrist/1 ). 20/

Aerosol and particulate matter (PM) particles can also be filtered and removed from the air using HVAC filters like MERV-13 or better, HEPA filters, build yourself CR-boxes with traditional fans or super quiet versions with PC fans. You can find guides and useful information on my website ( covid.gilchrist.ca ). 21/

Since you don't have control over the air quality in most public spaces you can also use personal filters (aka masks) with a good seal designed to protect from airborne pathogens like N95 respirators. To find out how well your mask seals, you can see my thread on fit testing ( mstdn.science/@jeffgilchrist/1 ) and some of the test results I got comparing masks ( mstdn.science/@jeffgilchrist/1 ). 22/

Some people misunderstand and think filters such as HEPA and mask material work like a sieve or chain link fence which allow smaller objects like flies to pass through. This thread explains how the laws of physics are used to allow the filtering material to stop such tiny smoke and aerosol particles ( mstdn.science/@jeffgilchrist/1 ). 23/