Thread by @jeffgilchrist

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/

An unrolled one-page web view for this long thread that may be easier to read or share can be found here ( ). 2/

https://twitter.com/jeffgilchrist/status/1701394815923916832

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 ( ). 3/

https://twitter.com/jeffgilchrist/status/1700854098755563660

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 ( ). H/T: @Daniel_E_Park 4/biorxiv.org/content/10.110…

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. 5/

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. 6/

** 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. 7/

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 ( ). 8/the-scientist.com/news-opinion/w…

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 - ). 9/

https://twitter.com/jeffgilchrist/status/1611333222419566594

Interesting side note that researchers are required to use pseudovirus because handling the real virus is dangerous to study even in a lab. 10/

Meanwhile the real virus is routinely found spreading throughout poorly ventilated indoor public spaces like schools and offices without any safety standards in place. 11/

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 ( ). 12/

https://twitter.com/jeffgilchrist/status/1700855496708653388

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. 13/

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. 14/

** Novavax Results **
Novavax 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. 15/

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. 16/

"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." 17/

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 by @Mike_Honey_ 18/

** Moderna Results **
Moderna also released a preprint of their updated XBB.1.5 booster performance with pseudovirus lab test results involving humans test subjects ( ). 19/medrxiv.org/content/10.110…

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. 20/

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 blood sera immune responses just before they got their updated booster with 15 days after the updated booster. 21/

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. 22/

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. 23/

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. 24/

Moderna found that vaccine adverse events were similar to those reported with their original and bivalent vaccines. 25/

** 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? 26/

@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 ( ). 27/

https://twitter.com/yunlong_cao/status/1653804044740341761

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 ( ). 28/

https://twitter.com/yunlong_cao/status/1653805038320635906

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. 29/

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. While it seems the updated Novavax and Moderna XBB.1.5 vaccines elicit antibodies... 30/

...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 to be recalled for the next exposure. 31/ Click "Show replies" 👇 to continue.

As @michaelzlin explains, for people who were never infected with an XBB or EG.5 variant, the XBB.1.5 booster will act like a priming event so may not be enough to protect against infection depending on the exposure level. 32/

If you then had an actual EG.5 or BA.2.86 infection after the XBB.1.5 booster, your immune system should produce antibodies rapidly enough to prevent more severe disease ( ). 33/

https://twitter.com/michaelzlin/status/1700925702923825309

The Novavax study provides a good example of how memory B cells will recall antibodies for specific variants it has been exposed to before. The original vaccine (Prototype) on its own (left side) produces antibodies with high levels of neutralization... 34/

for the original variant (first column) , but low levels for XBB.1.5 (third column). Similarly on the right side, the XBB.1.5 vaccine on its own produces antibodies with low levels of neutralization for the original variant but high for XBB.1.5. 35/

But when you had two doses of the original vaccine and then get an XBB.1.5 booster dose the antibodies that get produced have the highest neutralization for the original (Prototype) variant because earlier memory B cells for the original variant still exist... 36/

and were restimulated by the XBB.1.5 vaccine, explaining the high neutralization levels. The antibodies are now a mixture of old and new instead of mostly being targeted to newer variants. 37/

In order for your immune system to start focusing on the newer variants and storing more memory cells specifically targeting them, @yunlong_cao's study found you need multiple exposures. 38/

You can see the same thing in the Moderna results where the neutralization levels of the original variant (Ancestral D614G) is already high before the booster (similar to the post-booster levels of XBB.1.5) and... 39/

...then multiple times higher than the XBB.1.5 levels after the booster showing massive production of antibodies targeting the original variant still. 40/

@threadreaderapp please unroll