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Sep 12, 2023 41 tweets 9 min read Read on X
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/ Graphic of COVID variants. Image from: https://www.fnha.ca/about/news-and-events/news/hot-topics-questions-about-covid-19-virus-variants-here-are-some-answers
An unrolled one-page web view for this long thread that may be easier to read or share can be found here ( ). 2/
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/
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/
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/
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/ Humoral Responses Following XBB.1.5 Booster in Rhesus Macaques. (A) Pseudovirus neutralization titers in rhesus macaques boosted with XBB.1.5 approximately 8 months after Prototype or bivalent (Prototype + BA.5) priming regimens. Sera were collected two weeks after the booster dose. Open circles represent individual data points, solid bars represent group geometric mean titers, error bars represent 95% confidence intervals, and the horizontal dashed line represents the assay limit of detection (LOD). Image from: https://www.biorxiv.org/content/10.1101/2023.08.30.554497v1.full
"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/ Graph of top 7 COVID variant family frequencies from PCR test genomic sequencing. Visualization tool was created by @Mike_Honey_ ( https://app.powerbi.com/view?r=eyJrIjoiNzE5YzczODItMDQzMS00M2EzLWFjNWYtMjg3OTY3NTNhZDM3IiwidCI6ImRjMWYwNGY1LWMxZTUtNDQyOS1hODEyLTU3OTNiZTQ1YmY5ZCIsImMiOjEwfQ%3D%3D )
** 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/ Graphs of GM=geometric mean; GMFR=geometric mean fold rise at day 15 relative to pre-booster. GM-levels of neutralizing antibody titers were assessed at pre-booster and at day 15 post-vaccination for the monovalent (mRNA-1273.815) and bivalent (mRNA-1273.231) vaccines using a lentivirus-based pseudovirus assay as described previously3 and in the Supplementary Methods. Analyses were performed in all participants in the Per-protocol Set for Immunogenicity (those with and without prior SARS-CoV-2 infection), and in those with prior infection and without prior infection. Image from: https://www...
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/ Analysis of neutralizing antibody titers against variants in randomly-selected all participants (n=20) and in those with (n=10) and without (n=10) SARS-CoV-2 infection from mRNA-1273.815 arm using a research grade VSV-based pseudovirus assay (supplementary methods). **p≤0.01 and ****p<0.0001 by the Wilcoxon t-test. Dotted line denotes the limit of detection (20) of the assay. Image from: https://www.medrxiv.org/content/10.1101/2023.08.22.23293434v2.full-text
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/
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/
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/
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/ Pseudovirus neutralization in mice sera collected one week following primary series vaccination with two doses of monovalent Prototype, XBB.1.5, or XBB.1.16. Open circles represent individual data points, solid bars represent group geometric mean titers, error bars represent 95% confidence intervals, and the horizontal dashed line represents the assay limit of detection (LOD). Image from: https://www.biorxiv.org/content/10.1101/2023.08.30.554497v1.full
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/ Humoral Responses Following XBB.1.5 Booster in Rhesus Macaques. (A) Pseudovirus neutralization titers in rhesus macaques boosted with XBB.1.5 approximately 8 months after Prototype or bivalent (Prototype + BA.5) priming regimens. Sera were collected two weeks after the booster dose. Open circles represent individual data points, solid bars represent group geometric mean titers, error bars represent 95% confidence intervals, and the horizontal dashed line represents the assay limit of detection (LOD). Image from: https://www.biorxiv.org/content/10.1101/2023.08.30.554497v1.full
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/ Graphs of GM=geometric mean; GMFR=geometric mean fold rise at day 15 relative to pre-booster. GM-levels of neutralizing antibody titers were assessed at pre-booster and at day 15 post-vaccination for the monovalent (mRNA-1273.815) and bivalent (mRNA-1273.231) vaccines using a lentivirus-based pseudovirus assay as described previously3 and in the Supplementary Methods. Analyses were performed in all participants in the Per-protocol Set for Immunogenicity (those with and without prior SARS-CoV-2 infection), and in those with prior infection and without prior infection. Image from: https://www...
...then multiple times higher than the XBB.1.5 levels after the booster showing massive production of antibodies targeting the original variant still. 40/
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More from @jeffgilchrist

Feb 10
#Ottawa, #Ontario, #Canada Virus Update:

You can see in the graph, COVID makes up the majority of new hospitalizations due to #Flu, #RSV or #COVID throughout the year, and even stays ahead during winter respiratory virus season. 🧵1/ A line graph displaying the percentage of patients hospitalized due to COVID-19, Influenza, or RSV over time, from September 1, 2023, to January 26, 2025. The x-axis represents weeks within this period, and the y-axis shows percentages from 0% to 100%. The graph has three colored lines: blue for COVID-19, purple for Influenza, and teal for RSV. The graph shows fluctuations in the percentage of hospitalizations due to each cause over time, with COVID-19 consistently having the highest percentage, followed by Influenza and RSV.
New hospitalizations are increasing again. This last update was the first time Flu hospitalizations (42) were significantly higher than COVID (34) in the same week with RSV at 14 people. 2/ The bar chart shows the number of new hospitalizations per week in Ottawa from August 27, 2023, to January 26, 2025. The y-axis represents the number of patients, ranging from 0 to 100. The x-axis represents the weeks. The bars are color-coded: blue for COVID-19, purple for Influenza, and teal for RSV. The chart shows fluctuations in hospitalizations over time, with notable peaks around December 2023 and January 2025.
In Ottawa, test positivity for Flu A (bright green) has really increased, COVID is still in second place, but seasonal human coronavirus is almost the same level, followed by Entero/Rhinovirus, and then RSV for the top 5. 3/ A stacked area chart displaying the percentage of positive tests for various viruses over time, from October 1, 2022, to January 26, 2025. The x-axis represents weeks within this period, while the y-axis represents the percentage, cumulatively stacked to 100%. The chart features the following viruses, each depicted in a distinct color: COVID-19 (red), Entero/Rhinovirus (yellow), Seasonal human coronavirus (purple), RSV (green), Parainfluenza (all types) (blue), Influenza B (dark purple), Influenza A (light green), Human metapneumovirus (pink), and Adenovirus (dark blue). The data shows fluc...
Read 6 tweets
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Similar to #Canada, babies in the #UK are at higher risk for #hospitalization and #ICU admission from #COVID. Their data looks deeper at infants < 6 months old which have higher ER attendance, hospital admission and severe hospitalisation rates than the oldest adults 90+! 🧵1/
That data from the UK was taken from this pre-print study ( ). 2/medrxiv.org/content/10.110…
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#Ottawa, #Ontario, #Canada Virus Update:

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New hospitalizations also jumped a lot in the last two reporting weeks, not just due to #RSV but a big spike in #COVID as well.

Follow the latest updates here ( ). 3/ covid.gilchrist.ca/Ottawa.htmlThe bar chart shows the number of new hospitalizations per week in Ottawa from August 27, 2023, to December 22, 2024. The y-axis represents the number of patients, ranging from 0 to 100. The x-axis represents the weeks. The bars are color-coded: blue for COVID-19, purple for Influenza, and teal for RSV. The chart shows fluctuations in hospitalizations, with peaks around late 2023 and early 2024, and another peak towards the end of 2024.
A line graph displaying the percentage of patients hospitalized due to COVID-19, Influenza, or RSV over time, from September 1, 2023, to December 22, 2024. The x-axis represents weeks within this period, and the y-axis shows percentages from 0% to 100%. The graph has three colored lines: blue for COVID-19, purple for Influenza, and teal for RSV. COVID-19 consistently shows the highest percentage of hospitalizations, with fluctuations throughout the period.
Read 4 tweets
Dec 24, 2024
#Variant update for #Ontario, #Canada (to Dec 10, 2024)

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XEC is a combination of KP.3.3 and KS.1.1 that recombined together. MC.1 is a direct descendant of KP.3.1.1 with one spike mutation at T571I. To learn more about how variant naming works, you can read this article I wrote with @paulseaman31 ( ). 2/docs.google.com/document/d/1q0…
This Sankey graph shows the proportion of variants from PCR test genomic sequencing in Ontario since October 27, 2024. You can follow the lineage backwards to see where a variant is a descendant from. 3/ The Sankey diagram visually displays the evolution and distribution of sequenced genomes in Ontario, Canada, up to December 10, 2024. The diagram uses colored bars and curved lines to show the flow and relationships between different genome variants over time. Each variant is labeled, such as "XEC," "BA.2," "BA.2.86," "JN.1," "KP.3," and various sub-variants. These bars and lines illustrate the transitions and derivations from one variant to another. The total number of sequenced genomes depicted is 4,928. This visualization helps to underst...
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Dec 22, 2024
Population rate vs raw numbers

This is a good example of why it is useful to understand the importance of population *rate* and not just look at raw numbers. The first graph shows raw numbers and the second graph population rate. 🧵1/ #ED #Respiratory #Virus #Population #Ottawa Chart of Respiratory Related ED Visits by Week and Age (Ottawa, ON, Canada) with raw numbers
Chart of Respiratory Related ED Visits by Week and Age (Ottawa, ON, Canada) with population rate per 100K
Ottawa Public Health makes only the raw data available for All causes and respiratory-related emergency department visits to Ottawa hospitals by age group and week ( ). 2/open.ottawa.ca/datasets/ottaw…
If I take the data and plot all the ages together, you can at least see all of the age groups at the same time but it is just the raw numbers. 3/
Read 12 tweets

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