Back

If you want to learn more about how Novavax differs and some benefits it has compared to the mRNA vaccines including info about mixing mRNA and Novavax for even better results, see this thread ( https://mstdn.science/@jeffgilchrist/111041478929925403 ). 2/

While Pfizer has only put out a press releases about the lab performance of their fall boosters, Novavax has recently made their preprint study available for people to see the full details ( https://www.biorxiv.org/content/10.1101/2023.08.30.554497v1.full ). H/T: @daniel_e_park 3/

Looking at the methodology is important as it tells you what kind of previous variant exposure the test subjects had which helps you understand if it remotely resembles what your previous exposure experience may be.

The Novavax fall booster is based on the XBB.1.5 "Kraken" variant and testing was done on mice and non-human primates in the lab so their results are estimates of how the updated vaccine could perform. 4/

** Pseudoviruses **

The other thing to point out is that the tests are using pseudovirus which is an approximation of the real thing so they can be conducted in lower biosafety level labs. Pseudoviruses don't continue to replicate making them safer to study and their surface is replaced with those of the SARS-CoV-2 virus to help get insight into how it might infect cells ( https://www.the-scientist.com/news-opinion/what-pseudoviruses-bring-to-the-study-of-sars-cov-2-68457 ). 5/

Unfortunately pseudoviruses can't be used to fully simulate how the virus propagates or study mechanisms which the virus uses to circumvent the body's immune system (which COVID-19 uses multiple tricks to do - https://mstdn.science/@jeffgilchrist/109642512693828283 ). 6/

Interesting side note that researchers are required to use pseudovirus because handling the real virus is dangerous to study even in a lab. Meanwhile the real virus is routinely found spreading throughout poorly ventilated indoor public spaces like schools and offices without any safety standards in place.

You can learn more about additional layers of protection to help prevent you from being exposed to pathogens in the first place in this thread ( https://mstdn.science/@jeffgilchrist/111041507055982883 ). 7/

Many of the scenarios that Novavax used for the updated vaccine was the test subject first getting two bivalent (original + BA.5) doses (which were never commercially available to the public) and then one updated XBB.1.5 booster. People who got one mRNA bivalent BA.5 vaccine dose which was commercially available and also infected with a BA.5 variant may have an immune exposure in the same ballpark as this scenario. 8/

** Novavax Results **

Thankfully Novavax also included results with non-human primates were they tested a scenario with 2 original doses of vaccine and then a single XBB.1.5 booster which may be more likely for people who never got any kind of bivalent vaccine or Omicron COVID-19 infection. 9/

The good news is that despite there being multiple newer variants after XBB.1.5, one dose of the updated Novavax booster elicits antibodies that can neutralize XBB.1.5 as expected but also XBB.1.16 "Arcturus", XBB.2.3 "Acrux" and the EG.5.1 "Eris" variant which is currently dominant in many places. 10/

"Importantly, the XBB.1.5 booster was immunogenic irrespective of priming regimen, as the general population includes individuals primed with diverse vaccination and infection backgrounds." 11/

In Ontario, the variant families currently circulating the most are EG.5.1 "Eris", followed by XBB.1.9* "Hyperion", XABB.1.16* "Arcturus", still some XBB.1.5* "Kraken", XBB.2.3* "Acrux" and FL.1.5.1* "Fornax". Visualization tool was created by @mike_honey_
12/

** 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 ). 13/

Their participants all received 3 doses of the original Moderna mRNA vaccine and then 1 dose of the Moderna bivalent original/BA.5 booster dose. Participants then either received a monovalent XBB.1.5 booster or a bivalent XBB.1.5/BA.5 booster with a median time of 8 months from their 4th dose. They compared participant blood sera immune responses just before they got their updated booster with 15 days after the updated booster. 14/

Their first set of results looked at XBB.1.5, XBB.1.16 and older variants. The green bar graphs on the left are people who received a monovalent XBB.1.5 vaccine dose which is the one being made available to the public and the results to look at. While there was little neutralization activity of XBB.1.5 and XBB.1.16 before the updated booster, that increased significantly after the XBB.1.5 booster dose. 15/

Moderna also released results with newer variants using a different pseudovirus and only a subset of their participants. Similarly, the vaccine showed significantly increased neutralization levels for XBB.2.3.2, EG.5.1, FL.1.5.1 and BA.2.86 after the booster dose.

Moderna found that vaccine adverse events were similar to those reported with their original and bivalent vaccines.16/

** Immune Imprinting **

A number of people have been asking if the latest variants have changed so much, do we just need one booster dose of the updated vaccine or do we need two doses to be effective?

@yunlong_cao discovered people needed more than one exposure of Omicron to generate *new* Omicron specific memory immune cells instead of just recalling the antibodies for the original COVID-19 virus elicited by the original vaccines ( https://twitter.com/yunlong_cao/status/1653804044740341761 ). 17/

For people who haven't been exposed to Omicron variants (either by infection or getting a bivalent BA.5 vaccine) may need two booster doses to produce new memory B cells targeting the updated variant ( https://twitter.com/yunlong_cao/status/1653805038320635906 ). 18/

Novavax found that having 2 doses of bivalent vaccine instead of just the original resulted in even higher levels of neutralization for all of the latest variants since having two BA.5 exposures helped. Novavax never released a BA.5 bivalent vaccine so people would have had to be infected with one or two Omicron variants to get a similar kind of exposure. 19/

While it seems the updated Novavax and Moderna XBB.1.5 vaccines elicit antibodies that can neutralize these latest variants, it still remains to be seen what percentage of those XBB.1.5 specific antibodies become memory immune cells after just one booster dose to be recalled for the next exposure. 20/

The imprinting studies have looked at infection and vaccines (but not Novavax specifically) so I'm not sure if the Matrix-M adjuvant helps encourage the immune system to create a larger amount of new XBB specific memory cells or not for people without previous exposure. 21/