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Heterologous Boosters
A new NIH-sponsored study has been posted.  The study has a lot more than what is in the media today, but I haven't had a chance to digest it. (For instance, adverse events)  

The study is ongoing.  Neutralization results for the Delta variant were only available for Moderna. (Otherwise, neutralization results were for an early COVID version (WA-1).)

This must have been rushed out.  There are tables with data from 15-days post-booster but "in process" for 29-days post-booster.   Perhaps the FDA had this rushed so they could make a decision on the Moderna booster.


Quote:People who got the Moderna vaccine for their original shots and Moderna again for their booster appear to have gotten the best immune response, followed by those who got Pfizer boosted by Moderna and then Moderna boosted by Pfizer — although the increase in immune response with the mRNA vaccines was probably too small to really make a difference in protection in most groups.

The most significant finding suggested that people who initially got the J&J vaccine seem to have gotten the best response if they got Pfizer or Moderna as their booster.

NOTE: This study used a 100mg (full) dose of Moderna as a booster.   Moderna has applied to the FDA for a 50mg (half) dose of Moderna as a booster.

I notice in the study that those that got the Moderna boost had a shorter interval after their first vaccinations until the boost (basically 14-17 weeks versus 20-24 weeks for Pfizer and 18-21 for J&J).  This is noticeable in the neutralizing titers prior to booster (original Moderna vaccine patients:  Moderna booster (16.4 weeks): 88.7; J&J booster (19.3 weeks): 61.7;  Pfizer booster (22.9 weeks): 57.6).  This makes me a little leary of their multiplicative factor as a measure of how effective the boost was.

I also don't believe this study can give a good idea of how enduring the effectiveness is.

However, the boost is quite significant for the mRNA boosters.  The J&J boost for J&J takes a low number and makes it a bit better -- sorta like an fading Pfizer and not as good as a fading Moderna.
The interval between vaccination and booster confounds things. But a 100mg Moderna raised the numbers for a Moderna-vaccination by 10.2x (or 7.9x). A 100mg Pfizer raised the numbers for a Moderna-vaccination by 11.5x (or 9.7x).

If we guess that a 50mg Moderna booster will raise the numbers by less than a 100mg Moderna booster, then it would not be surprising if a 100mg Pfizer boosts a Moderna vaccination by more than a 50mg Moderna booster.
good summary article, IMO
This quote from the article is misleading "Dr. Lyke and her colleagues found that switching boosters raised the level of coronavirus antibodies, no matter which combination people got."

Boosters raised the level of antibodies whether the booster was the same or different. Generally, a Moderna booster increased the most, followed by Pfizer, followed by J&J. A J&J 2nd shot (the "booster") still didn't get the numbers as high as the mRNA 2-shot vaccinations even months later.

I don't know why they seemed to rank them by a factor increase (for instance, 10x) rather than just looking at the final numbers, or the just looking at the absolute change in the measures.

Also, I will add two clauses to clarify this statement, "The Centers for Disease Control and Prevention has no preference for which age-appropriate AND MEDICAL-CONDITION-APPROPRIATE flu vaccine people get AMONG THE FDA APPROVED VACCINES." (In particular, it seems the live, attenuated vaccine is not recommended for pregnant or immunocompromised or for certain other conditions.) There are 9 different vaccines.

I also think the article allows the reader to think the situation with COVID is potentially like the situation with influenza. As I understand it, the main reason for yearly influenza shots is that the prevalent influenza changes from year to year, and new shots are needed to cover the new variants. The current COVID boosters are to increase the antibodies, not to provide wider or different coverage of variants.

Personally, I am signed up to get Moderna booster monday; I originally received Janssen back in March.
I always wonder at how results get simplified so much.  And, how the authors sleep at night.

From that article

Quote:The team showed that SARS-CoV-2 infection rates in the mix-and-match [AstraZeneca + Pfizer] group were half that of the group that received two doses of Pfizer.
From the referenced study:

Quote:individuals who received each vaccination regimen (which started in January 2021
in both groups)...

Histograms show the infection rate among groups of healthcare workers who were vaccinated with the homologous BNT/BNT combination (n=81/10609) within the recommended 4-week timeframe between the two doses, or with the BNT boost after receiving the first ChAd dose (n=10/2512) approximately 12 weeks before.
Data show the infection that occurred after the 14-days post-boost period, up to the end of recording (08/15/2021). 

Things looked good until I saw that the group that had heterologous doses had an average of 85 days between the two doses, while the Pfizer+Pfizer group had an average of 29 days.   The article indicates both sets of first doses were started in January.  The incidence of COVID was counted for cases occurring 14 days after the second dose.

There seem to be at least two things wrong with that particular study:
  1) More days at risk.  The  higher incidence group was counted from (Jan 15 (as good as I can estimate from the article) 1st dose; Feb 13, 2nd dose; Feb 27 begins counting)  Feb 27 to Aug 15 (227-58 = 169 days), while the lower incidence group was counted from (Jan 15, 1st dose; Apr 10, 2nd dose; Apr 24 begins counting)  Apr 24 to Aug 15 (227-114 = 113 days).   So if risk was equal from Feb 27 to Apr. 24 as it was Apr 24 to Aug 15, the number of cases in the higher incidence group should have been decreased by about a third to compare with those in the lower incidence group.
  2) Unequal exposure.  Using the WHO's COVID Dashboard, I find that France had 38.7M cases on 2/27/21(day 58), 50.6M cases on 4/24/21 (day 113), 62.8M on 8/15/21 (day 227).  The higher incidence group was at risk of being counted during a period when the country had 24.1M cases in 169 days.  The lower incidence group was at risk of being counted during a period when the country had 12.2M cases in 113 days.  The population of France is about 65.27M at mid-year.  

Using the entire population of France is not ideal as a control group, but it is the best I can do to try to remove those issues.

There were 10,609 in the higher incidence group.  During their at-risk period, one would expect 24.1/65.27 of the group (ie, 3,917) to get sick.  Only 85 got sick, for an Pfizer+Pfizer effectiveness of 97.83% during the evaluated period.

There were 2,512 in the lower incidence group.  During their at-risk period, one would expect 12.2/65.27 of the group (ie, 470) to get sick.   Only 10 got sick, for an Az+Pfizer effectiveness of 97.87% during the evaluated period.

The effectiveness of a Pfizer booster seems virtually indistinguishable in the two groups.  I do not believe this study's results support anything more than a Pfizer booster worked equally well in both cases.
Thanks for working through all that. Makes me wonder who's behind the study.
Another study caught my eye regarding heterologous vs homologous boosters.
Association of Homologous and Heterologous Vaccine Boosters With COVID-19 Incidence and Severity in Singapore

Quote:Among individuals who received BNT162b2 [Pfizer] for their primary series, the incidences (per million person-days) of confirmed and severe infections were 227.9 and 1.4 for homologous-boosted
compared with 600.4 and 20.5 for nonboosted individuals. The IRRs were 0.272 (95% CI, 0.258-0.286) for the confirmed cases among homologous-boosted individuals and 0.047 (95% CI, 0.026-0.084) for severe cases.
For heterologous-boosted individuals, the incidences of confirmed and severe infections were 147.9 and 2.3 cases per million person-days, respectively, with IRRs of 0.177 (95% CI, 0.138-0.227) and 0.078 (95% CI, 0.011-0.560).

For individuals who received mRNA-1273 [Moderna] for their primary series, the incidence of confirmed infections for homologous-boosted individuals was 133.9 cases per million person-days (IRR, 0.198 [95% CI, 0.144-0.271]). For heterologous-boosted individuals, the incidence of confirmed infections was 100.6 per million person-days (IRR, 0.140 [95% CI, 0.052-0.376]). The number of severe infections among individuals receiving mRNA-1273 for their primary series was too small to assess IRRs.

The boosters were the same as in the US  (Pfizer: 30µg,  Moderna 50µg)

Note they used person-days at risk, avoiding one of my concerns about studies in earlier posts.

Ok, this is just one study, but it makes me feel that I nailed it.  I am in the group of initial Moderna, with a heterologous booster.  

[Image: jld220011t1_1647557355.29116.png?Expires...RDK6RD3PGA]
Another study has been posted, looking at different booster strategies for those that got J&J first shots.

Quote:Vaccine Effectiveness against COVID-19–associated emergency department/urgent care visits was 24% after 1 Jansen dose, 54% after 2 Jansen doses, and 79% after 1 Janssen/1 mRNA dose, compared to 83% after 3 mRNA doses. VE for the same strategies against COVID-19–associated hospitalization was 31%, 67%, 78%, and 90% respectively.
If you want to make your booster or 4th dose heterologous, you might have to insist. Kaiser did not want for me to switch to Moderna after Pfizer for by booster. I said "I insist. It is FDA approved." The technician frowned, went to her supervisor, came back, and said "They told me I'm allowed to do it!" with a tone that indicated surprised.

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