reSee.it - Tweets Saved By @jeffgilchrist
@jeffgilchrist - Jeff Gilchrist
COVID-19: Pediatric Diabetes, Lung Damage, Brain Impact, Newborns, and Higher Hospitalization Rates Studies show kids are also at risk of long-term consequences from infection and especially those <5 for higher rates of hospitalization than most adults. Let's take a look.🧵1/ https://t.co/ByAxr8XphO
@jeffgilchrist - Jeff Gilchrist
Novavax & Moderna XBB.1.5 Fall Booster Performance The table of contents and link for the unrolled one-page version of the thread can be found in the next tweet once it is posted. 👇
@jeffgilchrist - Jeff Gilchrist
The one page web view is available here: https://threadreaderapp.com/thread/1701396947871916279.html Start: Pseudoviruses: Novavax Results: Moderna Results: Immune Imprinting:
@jeffgilchrist - Jeff Gilchrist
Novavax & Moderna XBB.1.5 Fall Booster Performance This thread provides some data from preprint studies about how well the updated #Novavax and #Moderna #booster #vaccine performs on recent #variants including some details on #immune #imprinting. 🧵1/
@jeffgilchrist - Jeff Gilchrist
** Moderna Results ** Moderna also released a preprint of their updated XBB.1.5 booster performance with pseudovirus lab test results involving humans test subjects ( https://www.medrxiv.org/content/10.1101/2023.08.22.23293434v2.full-text ). 19/
@jeffgilchrist - Jeff Gilchrist
#Novavax vs mRNA vaccine This thread explains how @Novavax is different from the #Moderna and #Pfizer #mRNA #vaccines and describes some of the benefits such as broadened #variant recognition, more durable #immunity, and fewer side effects. 🧵1/
@jeffgilchrist - Jeff Gilchrist
An unrolled one-page web view for this long thread that may be easier to read or share can be found here ( ). 2/
@jeffgilchrist - Jeff Gilchrist
Novavax is a protein based vaccine (similar designs have also been used for many years for tetanus, diphtheria and hepatitis B). Novavax presents the full COVID-19 Spike protein in nanoparticles designed to mimic the structure of the virus itself ( https://novavax.com/science-technology/recombinant-protein-based-nanoparticle-vaccine-technology ). 3/
@jeffgilchrist - Jeff Gilchrist
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. 4/
@jeffgilchrist - Jeff Gilchrist
This video shows you how the mRNA Spikes are produced in your body ( https://www.youtube.com/watch?v=8nD6Q9X0SFw ). 5/
@jeffgilchrist - Jeff Gilchrist
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. 6/
@jeffgilchrist - Jeff Gilchrist
This adjuvant induces early activation of innate immune cells at the injection site and in the draining lymph nodes ( https://www.tandfonline.com/doi/full/10.1080/21645515.2023.2189885 ). H/T: @paulseaman31 7/
@jeffgilchrist - Jeff Gilchrist
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... 8/
@jeffgilchrist - Jeff Gilchrist
...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? 9/
@jeffgilchrist - Jeff Gilchrist
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). 10/
@jeffgilchrist - Jeff Gilchrist
This improvement was actually seen in the real world with the BA.1 and BA.5 variants and the original Novavax vaccine formula. 11/
@jeffgilchrist - Jeff Gilchrist
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. 12/
@jeffgilchrist - Jeff Gilchrist
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. 13/
@jeffgilchrist - Jeff Gilchrist
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. ( https://www.medrxiv.org/content/10.1101/2023.05.31.23290594v1.full ). 14/
@jeffgilchrist - Jeff Gilchrist
There have also been suggestions to improve mRNA vaccine potency, durability, safety and T-cell response by using adjuvants ( https://www.nature.com/articles/s41551-023-01082-6 ). 15/
@jeffgilchrist - Jeff Gilchrist
In mice they found the adjuvant in mRNA vaccines increased antibody levels 10x and produced Fc-binding antibodies which showed better control over viral replication and help predict resolution of severed COVID-19 ( ). 16/
@jeffgilchrist - Jeff Gilchrist
Many people have anecdotally discovered and reported that Novavax doses had much lower side effects than when they received an mRNA shot. 17/
@jeffgilchrist - Jeff Gilchrist
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 ( https://medrxiv.org/content/10.1101/2023.05.31.23290594v1.full ). H/T: @michaelzlin 18/
@jeffgilchrist - Jeff Gilchrist
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 19/
@jeffgilchrist - Jeff Gilchrist
* 22.4% lower swelling * 18.3% lower headache * 17.5% lower joint pain * 13% lower redness * 12% lower fever * 3.5% lower nausea/vomiting 20/
@jeffgilchrist - 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. 21/
@jeffgilchrist - Jeff Gilchrist
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"... 22/
@jeffgilchrist - Jeff Gilchrist
...with slower decay rate compared to an mRNA booster dose and less side effects than mRNA boosters ( https://www.tandfonline.com/doi/full/10.1080/14760584.2023.2232020 ). H/T: @Daniel_E_Park 23/
@jeffgilchrist - Jeff Gilchrist
A randomized controlled trial found that getting a Novavax dose after Pfizer mRNA elicited the highest humoral and peak cellular immune responses ( https://www.journalofinfection.com/article/S0163-4453(23)00330-4/fulltext ). H/T: @michaelzlin 24/
@jeffgilchrist - Jeff Gilchrist
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. 25/
@jeffgilchrist - Jeff Gilchrist
Neutralising antibodies against Omicron BA.1 and BA.2 were higher with Novavax after mRNA compared to two mRNA doses. 26/
@jeffgilchrist - Jeff Gilchrist
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. 27/
@jeffgilchrist - Jeff Gilchrist
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. 28/
@jeffgilchrist - Jeff Gilchrist
FYI, I do not work for Novavax or have any investments or make any money from Novavax selling products. 29/
@jeffgilchrist - Jeff Gilchrist
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. 30/
@jeffgilchrist - Jeff Gilchrist
While vaccines are important, they should be the last layer of protection to rely on in case all the other layers fail and you get exposed. Vaccines should not be the one and only layer governments all seem to be currently relying on. 31/ Click "Show replies" 👇 to continue.
@jeffgilchrist - Jeff Gilchrist
ASHRAE Standard 241, Control of Infectious Aerosols ( https://www.ashrae.org/technical-resources/bookstore/ashrae-standard-241-control-of-infectious-aerosols ) was released in July 2023 so this should now be adopted and required in air quality standards for buildings like governments already require clean drinking water standards for these same buildings.32/
@jeffgilchrist - Jeff Gilchrist
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 ( https://t.co/t9DLMBZiu9 ). 33/
@jeffgilchrist - Jeff Gilchrist
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. 34/
@jeffgilchrist - Jeff Gilchrist
You can find guides and useful information on my website ( http://covid.gilchrist.ca ). 35/
@jeffgilchrist - Jeff Gilchrist
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. 36/
@jeffgilchrist - Jeff Gilchrist
To find out how well your mask seals, you can see my thread on fit testing ( https://t.co/aTQfbtru41 ) and some of the test results I got comparing masks ( https://t.co/dSvpuaoeKM ). 37/
@jeffgilchrist - Jeff Gilchrist
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. 38/
@jeffgilchrist - Jeff Gilchrist
This thread explains how the laws of physics are used to allow the filtering material to stop such tiny smoke and aerosol particles ( https://t.co/tvw0UorQzy ). 39/
@jeffgilchrist - Jeff Gilchrist
COVID-19: How good is a Novavax booster and with previous mRNA doses? This long thread explores what kind of immune response a Novavax booster is giving people as a primary series and after 2 or 3 mRNA doses in recent studies, and what some of the benefits seem to be. 🧵1/
@jeffgilchrist - Jeff Gilchrist
The majority of people in North America and many parts of the world have had mRNA COVID-19 vaccines from Moderna or Pfizer but another type of vaccine (Novavax) has been making waves since its approval. 2/
@jeffgilchrist - Jeff Gilchrist
Novavax is a protein subunit vaccine that presents purified parts of the Spike protein, where mRNA vaccines get your cells to produce copies of the entire Spike protein. Protein based vaccines have been used for many years including for tetanus, diphtheria and hepatitis B. 3/
@jeffgilchrist - Jeff Gilchrist
The Novavax proteins are actually created in a type of moth cell. Since protein subunits on their own don't elicit a strong immune response, the vaccine also uses an adjuvant (made from soapbark tree) to increase the response which is a common technique used in vaccines. 4/
@jeffgilchrist - Jeff Gilchrist
The proteins are assembled into nanoparticles designed to mimic the structure of the COVID-19 virus as shown in the diagram. More details on how the Novavax vaccine is produced can be found here ( https://www.novavax.com/science-technology/recombinant-protein-based-nanoparticle-vaccine-technology ). 5/
@jeffgilchrist - Jeff Gilchrist
Sections of Spike protein that Novavax chose have been well conserved (97%) across multiple variants (Wuhan, BA.1, BA.2, BA.4) so the original formula is actually holding up very well against the latest Omicron variants ( https://youtu.be/BFdzNUus_CE?t=11619 ). H/T: @SocialFuzzer 6/
@jeffgilchrist - Jeff Gilchrist
In addition to Novavax holding up better against newer variants, its protection also seems to last longer before waning. 7/
@jeffgilchrist - Jeff Gilchrist
Novavax presented to the FDA in June 2022 showing that efficacy against variants of interest and variants of concern remained high despite the virus undergoing significant mutation ( https://youtu.be/BFdzNUus_CE?t=11603 ). 8/
@jeffgilchrist - Jeff Gilchrist
Strong protection against any infection (symptomatic and asymptomatic illness) remained above 71% (USA/Mexico) and 83% (UK) after 6 months. Every dose of vaccine allows the immune system to identify and learn about more sections of the protein. 9/
@jeffgilchrist - Jeff Gilchrist
With Novavax using better conserved proteins, after 3 doses it has a huge increase in neutralization ability even against variants such as BA.1 (purple) and BA.4/5 (blue) ( https://www.medrxiv.org/content/10.1101/2022.11.18.22282414v1.full-text ). 10/
@jeffgilchrist - Jeff Gilchrist
After the 4th dose of Novavax, they reach levels seen in the clinical trial against the original Wuhan variant (which Novavax calls their prototype vaccine) that provided 95% efficacy. 11/
@jeffgilchrist - Jeff Gilchrist
What is really interesting is that you can see in the antigenic cartography diagram that additional doses reduce antigenic distance for broader recognition of new variants ( https://www.medrxiv.org/content/10.1101/2022.11.18.22282414v1.full-text ). 12/
@jeffgilchrist - Jeff Gilchrist
With 2 doses of Novavax, there is a 33.5x difference between the original Wuhan variant and BA.4/5, which decreases to 7.1x after 3 doses, and only 3.5x after 4 doses which they attributed to the conserved parts of the spike protein between the variants. 13/
@jeffgilchrist - Jeff Gilchrist
Is Novavax working on a BA.1 specific or Bivalent vaccine like Pfizer/Moderna? They have actually tested both versions of a vaccine but since the spike proteins they used are so conserved between variants, the original vaccine formula performed just as well... 14/
@jeffgilchrist - Jeff Gilchrist
...as both the BA.1 specific and bivalent vaccines against BA.5 so did not warrant them asking the FDA to approve an updated bivalent formula in the summer ( https://filecache.investorroom.com/mr5ir_novavax2/187/download/3Q22-FINAL.pdf ). 15/
@jeffgilchrist - Jeff Gilchrist
People who started with Novavax and got 4 doses seem to be in a very good place but what about all the people who started getting mRNA (Moderna/Pfizer) or adenovirus (J&J/AZ) doses? How does adding Novavax doses compare for this group? 16/
@jeffgilchrist - Jeff Gilchrist
Novavax has been doing clinical trials with those groups as well. With 2 doses of Moderna or Pfizer, 1 dose of J&J and then receiving 1 Novavax booster were able to obtain Spike IgG antibody levels similar to the 2 dose Novavax phase 3 trials ( https://filecache.investorroom.com/mr5ir_novavax2/187/download/3Q22-FINAL.pdf ). 17/
@jeffgilchrist - Jeff Gilchrist
The graph shows for people with 3 doses of Moderna or Pfizer, 2 doses of J&J and then receiving 1 Novavax booster were above to get higher levels of IgG antibodies than the Novavax phase 3 trial ( https://filecache.investorroom.com/mr5ir_novavax2/187/download/3Q22-FINAL.pdf ). 18/
@jeffgilchrist - Jeff Gilchrist
How do 3 mRNA vaccine doses and a Novavax booster compare with the newer Omicron BA.1 and BA.5 variants? As you can see from the graph antibody levels with BA.1 and BA.5 are higher than the levels which achieved 88% vaccine efficacy ( https://filecache.investorroom.com/mr5ir_novavax2/187/download/3Q22-FINAL.pdf ). 19/
@jeffgilchrist - Jeff Gilchrist
Another study also looked at the response to the Omicron BA.1 and BA.5 variants for people who had 2 mRNA or 3 mRNA doses and then a Novavax booster dose ( https://www.journalofinfection.com/article/S0163-4453(22)00548-5/fulltext ). 20/
@jeffgilchrist - Jeff Gilchrist
They found that neutralization levels against BA.5 increased after the Novavax dose by: 3.8x = 2 mRNA + Novavax 2.5x = 3 mRNA + Novavax (not previously infected) 1.4x = 3 mRNA + Novavax (previously infected) 21/
@jeffgilchrist - Jeff Gilchrist
As found in previous studies, neutralization levels for those previously infected + vaccinated were much higher than those who had never been infected before. 22/
@jeffgilchrist - Jeff Gilchrist
Someone with 3 mRNA doses who were previously infected and received a Novavax booster dose did not significantly increase their antibody levels but hit some kind of ceiling. 23/
@jeffgilchrist - Jeff Gilchrist
While antibody levels may not be higher, it still may be possible that the immune system is learning more about the conserved regions of the spike so it may produce better quality antibodies. 24/
@jeffgilchrist - Jeff Gilchrist
The mRNA vaccines seem to provide a stronger reaction than most vaccines in the form of a very sore arm and other side effects so how does Novavax compare? 25/
@jeffgilchrist - Jeff Gilchrist
I have seen many reports from people saying they barely felt anything, no sore arm or for a very short period of time, nothing compared to their mRNA vaccine experience. 26/
@jeffgilchrist - Jeff Gilchrist
Surveillance reports also seem to be indicating the same thing, the AEFI report from Ontario to Nov. 20, 2022 shows that after 12,422 doses of Novavax given only a very small number of serious adverse events reported ( https://www.publichealthontario.ca/-/media/documents/ncov/epi/covid-19-aefi-report.pdf?la=en ). 27/
@jeffgilchrist - Jeff Gilchrist
The mRNA vaccines do not elicit very good mucosal immunity which are IgA antibodies located in the mucosa (nose, upper airways, etc..) where the virus enters your body. 28/
@jeffgilchrist - Jeff Gilchrist
Nasal vaccines are being developed to target this type of immunity but it seems that Novavax might actually elicit IgA antibodies as well. 29/
@jeffgilchrist - Jeff Gilchrist
Novavax found easily detectable levels of IgA antibodies in the mucosa of non-human primates after being vaccinated which may help explain why the efficacy is so high and could be providing sterilizing immunity ( https://youtu.be/BFdzNUus_CE?t=12507 ). 30/
@jeffgilchrist - Jeff Gilchrist
Novavax provides an alternative to other existing COVID-19 vaccines and since it uses more conserved regions of the spike protein, it continues to work well with newer variants, the protection wanes more slowly than other vaccines... Click "Show replies" 👇to continue. 31/
@jeffgilchrist - Jeff Gilchrist
...people react less and have less side effects. The key is that you need multiple doses over time for your immune system to learn enough parts of the spike to identify it easily in newer variants. 32/
@jeffgilchrist - Jeff Gilchrist
In Canada, Novavax is approved as a primary series and booster dose for adults 18+ ( https://www.canada.ca/en/health-canada/services/drugs-health-products/covid19-industry/drugs-vaccines-treatments/vaccines/novavax.html ). 33/
@jeffgilchrist - Jeff Gilchrist
You can watch the entire Novavax presentation to the FDA on June 28, 2022, starting here: https://youtu.be/BFdzNUus_CE?t=11477 34/
@jeffgilchrist - Jeff Gilchrist
* Please note that I do not work for Novavax, do not have any investments or make any money from Novavax so no conflict of interest. 35/
@jeffgilchrist - Jeff Gilchrist
If you would like to share this thread with people outside of Twitter, you can use this link: https://pingthread.com/thread/1597228107919826946
@jeffgilchrist - Jeff Gilchrist
I wanted to clarify some wording that I used earlier in this thread that I can't edit now (thanks Twitter!) so it is accurate. Anywhere that refers to Novavax using more conserved parts of the spike protein should actually be... 36/
@jeffgilchrist - Jeff Gilchrist
...the antibodies elicited by the Novavax vaccine seem to bind to more conserved parts of the spike protein (epitopes) which may explain why it has higher neutralization against Omicron BA.5 even with the original formula. 37/
@jeffgilchrist - Jeff Gilchrist
The actual spike protein used by Novavax is the full spike except they modify the Furin Cleavage Site (FCS) so it can't be cut into separate S1 and S2 proteins. 38/
@jeffgilchrist - Jeff Gilchrist
The mRNA vaccines elicit antibodies for both S1 and S2 which is different than Novavax. With the mRNA vaccines your cells produce the full spike protein ( https://youtube.com/watch?v=8nD6Q9X0SFw ). 39/
@jeffgilchrist - Jeff Gilchrist
The Novavax vaccine presents the full spike but they are arranged around a core so may interact differently with the immune system than mRNA produced spikes ( https://www.novavax.com/science-technology/recombinant-protein-based-nanoparticle-vaccine-technology ). 40/
@jeffgilchrist - Jeff Gilchrist
From the FDA VRBPAC meeting in June 2022, Dr. Marasco comments that the form of the Novavax protein with an adjuvant is able to produce antibodies that have broader capability ( ). H/T: @paulseaman31 41/
@jeffgilchrist - Jeff Gilchrist
From the 4th dose study, "We believe this phenomenon may be driven by the conserved epitopes found on the recombinant protein vaccine whereby expression of the full-length trimers of the spike protein..." 42/
@jeffgilchrist - Jeff Gilchrist
"... present epitopes that are conserved across variants for recognition by the immune system." ( https://www.medrxiv.org/content/10.1101/2022.11.18.22282414v1.full ) 43/
@jeffgilchrist - Jeff Gilchrist
** UPDATE ** this thread contains updated information on the Novavax vaccine from Jan. 26, 2023 including data on how well it compares to mRNA vaccines for BQ.1.1 and XBB.1 variants and data from the adolescent 12-17 clinical trial. See here ( https://t.co/2fdGqKNMX0 ). 44/