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Jeff Gilchrist @jeffgilchrist.bsky.social · 4h

Part 4 “Nuvaxovid: Effectiveness and Immunocompromised People” is now available from @paulseaman.bsky.social at ( bsky.app/profile/paul... ).

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Reposted by Jeff Gilchrist

Paul Seaman @paulseaman.bsky.social · 7h

Nuvaxovid: Effectiveness and Immunocompromised People This is part 4 of 7 from @jeffgilchrist.bsky.social and my document compiling available information setting out some of the main differences between #Nuvaxovid and the more common mRNA based #COVID vaccines.🧪🧵1/ (formerly #Novavax)

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Reposted by Jeff Gilchrist

Jeff Gilchrist @jeffgilchrist.bsky.social · 08/10/2026

Information for (or give to) Pharmacists on how to get Nuvaxovid in Canada #Nuvaxovid is a protein-based COVID vaccine approved for ages 12 and older and is back in Canada after 2 years now that Sanofi Canada took ownership of the vaccine. 🧵1/ (formerly #Novavax)

An image showing a white packaging box and a single pre-filled syringe for Sanofi's COVID-19 Vaccine, Adjuvanted Nuvaxovid (2026–2027 Formula)

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Reposted by Jeff Gilchrist

Jeff Gilchrist @jeffgilchrist.bsky.social · 15/10/2026

You can also point pharmacies to this document if they have any questions about the public program, "Are you a pharmacy with a question about the Publicly Funded Vaccine Programs in Ontario?" See ( www.ontario.ca/files/2026-0... )

Flow chart showing how pharmacies can get in contact with the right people to learn more about the public vaccine program in Ontario.

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Jeff Gilchrist @jeffgilchrist.bsky.social · 15/10/2026

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Jeff Gilchrist @jeffgilchrist.bsky.social · 15/10/2026

Since we will be posting each section from the document as separate threads, part 4 “Nuvaxovid: Effectiveness and Immunocompromised People” will be coming out shortly from @paulseaman.bsky.social and the link will be added to the end of this thread once it is posted.

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Jeff Gilchrist @jeffgilchrist.bsky.social · 15/10/2026

also another study showing a clear IgG4 rise in rhesus macaques whether they received three mRNA or two mRNA and then a Nuvaxovid booster, and moreso with a third Nuvaxovid ( www.science.org/doi/10.1126/... ) [Novavax affiliated].

science.org

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Jeff Gilchrist @jeffgilchrist.bsky.social · 15/10/2026

• A study that generally accepts that the rise is detrimental to antibody function and presents data suggesting little or no such rise is seen with repeated Nuvaxovid boosters in humans ( www.journalofinfection.com/article/S016... ) [Novavax affiliated]

journalofinfection.com

Altered IgG4 antibody response to repeated mRNA versus recombinant protein SARS-CoV-2 vaccines

Dear Editor,

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Jeff Gilchrist @jeffgilchrist.bsky.social · 15/10/2026

• Arguing that the higher IgG4 proportion seen does negatively affect antibody function ( www.sciencedirect.com/science/arti... )

sciencedirect.com

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Jeff Gilchrist @jeffgilchrist.bsky.social · 15/10/2026

• Showing the IgG4 rise after repeated mRNA doses and further boost after infection ( www.science.org/doi/10.1126/... )

science.org

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Jeff Gilchrist @jeffgilchrist.bsky.social · 15/10/2026

This is a complex topic and larger scientific discussion that is still unfolding and beyond the scope of this information summary. However, if you are interested in further reading, there are some papers that can be referred to:

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Jeff Gilchrist @jeffgilchrist.bsky.social · 15/10/2026

others say that even where more IgG4 is seen, overall antibody performance still looks strong and so the real-world importance is unclear. A few studies have suggested higher IgG4 levels are linked to a slightly higher chance of later infection.

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Jeff Gilchrist @jeffgilchrist.bsky.social · 15/10/2026

IgG4 antibodies are generally thought to be less good at performing certain jobs that antibodies are supposed to do. Some researchers worry this could weaken protection;

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Jeff Gilchrist @jeffgilchrist.bsky.social · 15/10/2026

Several studies show this tends to rise after multiple mRNA doses, often stronger in people who were vaccinated first and were later infected. So far, the same rise has not been seen with the protein-based Nuvaxovid vaccine.

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Jeff Gilchrist @jeffgilchrist.bsky.social · 15/10/2026

The second issue we are closely following is where, after receiving repeated mRNA COVID boosters, the share of a particular class of antibody called IgG4 is seen to increase.

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Jeff Gilchrist @jeffgilchrist.bsky.social · 15/10/2026

...yet the overall reactogenicity profile of mRNA vaccines stayed higher than what is typically seen with the protein-based Nuvaxovid.

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Jeff Gilchrist @jeffgilchrist.bsky.social · 15/10/2026

Overall, this data suggests that the combined attempt at dose sparing and focusing the antigen in mRNA with mNEXSPIKE, without adding a new adjuvant, helped a little bit both with effectiveness and reducing local reactions...

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Jeff Gilchrist @jeffgilchrist.bsky.social · 15/10/2026

Real-world data from the 2025-2026 season in adults 65 and older who received the updated mNEXSPIKE vaccine show reduced hospitalisations by about 59% (and 67% in 75 and older).

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Jeff Gilchrist @jeffgilchrist.bsky.social · 15/10/2026

Whether or not these differences with mNEXSPIKE have an effect on preventing severe disease is unclear, but it is an interesting difference to consider.

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Jeff Gilchrist @jeffgilchrist.bsky.social · 15/10/2026

Studies have found that mNEXSPIKE also does create a useful CD4+ and CD8+ response, but of course again this is limited to the parts of the Spike protein that T cells are equipped to see, and the vaccine includes, so that the immune system can actually examine and learn about them.

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Jeff Gilchrist @jeffgilchrist.bsky.social · 15/10/2026

Once enough trackers are attached to a flag, a security team (various immune cells) can follow the signal coming from the tracker to the compromised house, and either demolish the house itself, or clear it out so the burglars can no longer use it as a base.

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Jeff Gilchrist @jeffgilchrist.bsky.social · 15/10/2026

Non neutralizing antibodies are like tracking devices that stick to those flags.

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Jeff Gilchrist @jeffgilchrist.bsky.social · 15/10/2026

You can think of an infected cell as a house that has been taken over by burglars (the virus). The cell reacts by hanging the burglars’ flag (the Spike protein) out the windows to alert the immune system that the cell is infected.

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Jeff Gilchrist @jeffgilchrist.bsky.social · 15/10/2026

This is because the immune system can still take notice of other areas and target them in a way that helps control an active infection.

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Jeff Gilchrist @jeffgilchrist.bsky.social · 15/10/2026

This is accomplished by the immune system examining the entire Spike protein, including the parts that do not include any locks that keys can be made to defeat the virus itself.

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Jeff Gilchrist @jeffgilchrist.bsky.social · 15/10/2026

...may provide neutralization to more areas of the Spike protein, but also an additional layer of antibody protection that may help prevent severe disease.

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Jeff Gilchrist @jeffgilchrist.bsky.social · 15/10/2026

We are currently following two issues. The first issue is whether vaccines which include the full Spike protein (like Nuvaxovid and the original design mRNA vaccines, Spikevax and Comirnaty)...

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Jeff Gilchrist @jeffgilchrist.bsky.social · 15/10/2026

We also wonder if using different vaccine types creates a diverse repertoire of antibodies, and in turn a different epitope mask may also be created and allow the immune system to epitope spread in a more comprehensive, diverse, or efficient way.

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Jeff Gilchrist @jeffgilchrist.bsky.social · 15/10/2026

...to more areas of the Spike protein, even if a large increase in the amount of total antibodies is not seen.

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Jeff Gilchrist @jeffgilchrist.bsky.social · 15/10/2026

While at this stage it is very difficult to examine this issue and come to any firm conclusions, it at least seems possible that using different vaccine types could help produce better quality antibodies...

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Jeff Gilchrist @jeffgilchrist.bsky.social · 15/10/2026

This study also had some interesting suggestions on antibody decay which we discuss in the “Durability” section below.

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Jeff Gilchrist @jeffgilchrist.bsky.social · 15/10/2026

Viral vector COVID vaccines such as those from AstraZeneca and Johnson & Johnson use another virus (adenovirus from chimpanzee or human) as a delivery system to introduce a piece of DNA encoding the COVID spike protein antigen into the cells of the vaccinated individual.

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Jeff Gilchrist @jeffgilchrist.bsky.social · 15/10/2026

Yet another study reviewed data generated from other prior studies.

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Jeff Gilchrist @jeffgilchrist.bsky.social · 15/10/2026

Antibody levels at 132 and 236 days were similar for all vaccination combinations. The study also found fewer moderate and severe systemic adverse effects for Nuvaxovid than Pfizer mRNA

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Jeff Gilchrist @jeffgilchrist.bsky.social · 15/10/2026

This study found that getting Nuvaxovid as a second dose elicited the highest humoral and peak cellular immune responses at 14 days and led to an 89% reduction in risk of self-reported breakthrough infection, up to 132 days.

Fig. 4 Kaplan–Meier curves for risk of self-reported SARS-CoV-2 infections during follow-up. B: seronegative participants randomised before 29th November 2021;

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Jeff Gilchrist @jeffgilchrist.bsky.social · 15/10/2026

Interestingly, someone previously infected who received 3 mRNA doses and who then received a Nuvaxovid booster dose did not significantly increase their antibody levels, but instead seemed to hit some kind of ceiling:

Fig. 2 Anti-SARS-CoV-2 spike protein (anti-S) IgG antibody kinetics, stratified by previous SARS-CoV-2 infection status. Anti-S antibody titers in samples obtained from 41 participants before fourth dose (T0) and 3 weeks (T1) and 3 months (T2) after the fourth dose. Median titers (black bars) are shown numerically. P-value resulting from Wilcoxon test (*p < 0.05, **p < 0.01, ***p < 0.001).

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Jeff Gilchrist @jeffgilchrist.bsky.social · 15/10/2026

This study found that neutralization levels against BA.5 increased after the Nuvaxovid dose by: 3.8x = 2 mRNA + Nuvaxovid 2.5x = 3 mRNA + Nuvaxovid (not previously infected) 1.4x = 3 mRNA + Nuvaxovid (previously infected)

Fig. 1 Neutralization titers against wild-type Wuhan-1 strain and Omicron subvariants BA.1 and BA.5 in individuals who received the third or fourth dose vaccination with NVX-CoV2373. In panel A, upper part shows neutralization titers against wild-type Wuhan-1 strain and Omicron subvariants BA.1 and BA.5 in six infection-naive individuals before (T0) and at three weeks (T1) after the third dose of vaccination with NVX-CoV2373 excluding three anti-N antibody-positive recipients. Lower part of panel A shows neutralization titers against wild-type Wuhan-1 strain and Omicron subvariants BA.1 and BA.5 in nine infection-naive and nine prior-infected individuals before (T0) and at three weeks (T1) after the fourth dose of vaccination with NVX-CoV2373. Fold-changes of geometric mean titers are presented in panel A. In Panel B, neutralizing antibody titers against wild-type Wuhan-1 strain and Omicron subvariants BA.1 and BA.5 are compared at each time point (T0 and T1) depending on prior infection and vaccine dose (third versus fourth). Median titers (horizontal black lines) are presented with the median titer values. The median neutralizing titer (ND50) was defined as the concentration of the antibodies that reduced the number of viruses by 50%.

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Jeff Gilchrist @jeffgilchrist.bsky.social · 15/10/2026

...but after two initial doses of Nuvaxovid those who received either a third homologous Nuvaxovid dose or heterogeneous mRNA vaccine dose saw significantly better neutralization against BA.2 (turquoise):

Fig. 3. Administration of a booster dose rescues neutralization potency against Omicron sublineages for all vaccines.
Plasma neutralizing antibody titers elicited by COVID-19 vaccine boosters determined using SARS-CoV-2 S VSV pseudotypes and VeroE6/TMPRSS2 as target cells. Three-dose (3×) mRNA-1273 or BNT162b2 samples (n = 13) were donated 13 to 97 days (mean, 30) after third dose; 2× NVX-CoV2373 plus 1× BNT162b2 or NVX-CoV2373 samples (n = 5) were donated 14 to 20 days (mean, 15) after third dose; 1× Ad26.COV2.S plus 1× Ad26.COV2.S or BNT162b2 samples (n = 14) were donated 12 to 16 days (mean, 14) after second dose; 2× AZD1222 plus 1× BNT162b2 or mRNA-1273 samples (n = 18) were donated 30 to 123 days (mean, 87) after third dose; 2× Sputnik V plus 1× AZD1222 or BNT162b2 samples (n = 14) were donated 45 to 60 days after third dose; and 2× BBIBP-CorV plus 1× BNT162b2 or mRNA-1273 samples (n = 18) were donated 29 to 89 days (mean, 50) after third dose. Individual points are representative geometric mean titers from two to four independent experiments consisting of two replicates each. Bars represent geometric means, and error bars represent geometric standard deviations for each group. Statistical significance between groups of paired data was determined by Wilcoxon rank sum test. **P < 0.01; ***P < 0.001; ****P < 0.0001. Patient demographics are shown in table S4. Normalized curves and fits are shown in fig. S8.

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Jeff Gilchrist @jeffgilchrist.bsky.social · 15/10/2026

Interestingly, while the study found that neutralization dropped off significantly when looking at two doses of any vaccine, and administering a third dose of mRNA vaccine restored protection somewhat (navy blue)...

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Jeff Gilchrist @jeffgilchrist.bsky.social · 15/10/2026

For example, one small early study looked at how well the blood from people who had been infected or vaccinated with various combinations of vaccines could neutralize early Omicron variants, up to BA.5 ( www.science.org/doi/10.1126/... ).

science.org

Omicron spike function and neutralizing activity elicited by a comprehensive panel of vaccines

The increasingly prevalent Omicron BA.4/BA.5 sublineages exhibit enhanced receptor binding and escape from neutralizing antibodies.

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