The promise of Mix and Match COVID-19 vaccinations

[AussieNeil]

A couple of papers published in Nature provide some encouraging indications of why a 'mix and match' strategy with vaccination boosters may broaden the protective immune response, perhaps giving us a critical edge in beating a COVID-19 infection. I consider that this approach will be increasingly important in providing adequate protection against new variants. While antivirals and monoclonal antibodies are particularly important for the CLL community, given we can't rely on our immune systems, at least our immune systems are dynamic and multilayered, with vaccinations providing, we hope, sentinel memory B and T cells to respond to infections potentially years after vaccination. Antivirals and monoclonal antibodies are unfortunately proving less effective against new coronavirus variants, resulting recommendations being withdrawn or higher doses required, limiting their coverage - and that's if you can find them! For details, see our maintained pinned post on this topic: healthunlocked.com/cllsuppo...

The conclusion of Homologous and Heterologous Covid-19 Booster Vaccinations: nature.com/articles/s41541-... states; "Heterologous prime–boost strategies may offer immunologic advantages to extend the breadth and longevity of protection provided by the currently available vaccines. The administration of a heterologous two-dose regimen of an adenovirus-vectored vaccine (ChAdOx1, Oxford–AstraZeneca) followed by an mRNA vaccine was more immunogenic than a two-dose homologous ChAdOx1 vaccine regimen.18-21 An option to use heterologous booster vaccines could simplify the logistics of administering such vaccines, since the booster formulation could be administered regardless of the primary series."

A second paper Distinguishing features of current COVID-19 vaccines: knowns and unknowns of antigen presentation and modes of action notes in the conclusion that of the vaccines used for mass immunization at date July 9, 2021, "They all proved to exceed initial hopes and maximal expectations of 50 % protection 143,144, displaying efficacies in preventing clinical disease of more than 90% in certain instances."nejm.org/doi/full/10.1056/N...

From the section Distinguishing features of vaccines independent of immunogen structure, with my emphasis; "As outlined in the preceding sections, substantial differences appear to exist among current vaccines that can affect the conformation of S and its presentation to the immune system. Independent of such antigenic effects, the fundamentally different mechanisms of action and ways of production are likely to introduce additional variation to the characteristics of immune responses and possible adverse reactions. Adenovirus-vector and mRNA vaccines promote substantially different innate responses that will certainly influence the nature of adaptive immune responses43. There is evidence that the Oxford-AstraZeneca vaccine might induce higher levels of specific T cells, whereas mRNA vaccines might induce higher antibody titers115,116,117. The relevance of these differences for protection are not yet clear. Similarly, immune responses to protein-based vaccines are shaped by the adjuvant used, for example by shifting CD4 T cells towards either Th1 or Th2118,119. For meaningful conclusions, studies on these topics will require head-to-head comparisons of vaccines, and corresponding publications are expected to expand rapidly in the near future. Here, we briefly discuss existing data and describe distinguishing features that can contribute to differences among vaccine responses independent of the structure and presentation of the S immunogen."

Given the comments about the Oxford-AstraZeneca vaccine, I'm now feeling less disappointed at only being able to have these when I had zero B cells following treatment. Similar comments about improved T cell effectiveness have been made about the Johnson and Johnson vaccine: npr.org/sections/health-sho...

Irrespective, investigations into the varying effectiveness of different vaccines are teaching us far more about how our immune system works (or doesn't work when we have CLL). Not only will this research result in more effective vaccines for diseases and potentially cancer, it should improve our overall understanding of how our bodies respond to infections. That can only be good news in helping researchers find ways to reduce our heightened risk of serious infections - sadly still a major factor reducing our anticipated life expectancy.

Neil

[Potplant]

Very helpful, as ever, Neil. Thank you. Linda 🙂

[bennevisplace]

Thanks for compiling this Neil.

In the UK many of us will have had 2 x Astrazeneca followed by 2 x Pfizer. Others will have had only mRNA combinations. The government recently ordered 16 million Novavax, a traditional protein-based vaccine, probably to persuade mRNA sceptics rather than following the science of heterogeneous vaccination.

I want to question your statement

Antivirals and monoclonal antibodies are unfortunately proving less effective against new coronavirus variants,

as I don't know of any study that shows antiviral treatments to be less effective. Yet.

Also,. the new monoclonal antibody treatment bebtelovimab is innocent until proven guilty

biorxiv.org/content/10.1101...

Talking of antivirals, I seem to remember that bkoffman's order of preference was 1. Paxlovid, 2. Remdesivir 3. Molnupiravir.

[AussieNeil Partner Administrator in reply to bennevisplace]

The antivirals are so far holding up better than the monoclonal antibodies, but per:

ncbi.nlm.nih.gov/pmc/articl...

The omicron variant has mutations in both the RNA-dependent RNA polymerase (RdRp) and the main protease of SARS-CoV-2, which are targets for antiviral drugs such as RdRp inhibitors (remdesivir and molnupiravir) and the main protease inhibitor PF-07304814,5 which arouses concern regarding the decreased effectiveness of these drugs against omicron. Thus, we tested three different antiviral compounds (i.e., remdesivir, molnupiravir, and PF-07304814) for their efficacy against omicron. The in vitro 50% inhibitory concentration (IC50) values of each compound were determined against NC928, NC002, HP127, HP01542, TY7-503, and UW5250. The susceptibilities of omicron to the three compounds were similar to those of the early strain (i.e., IC50 values for remdesivir, molnupiravir, and PF-07304814 that differed by factors of 1.2, 0.8, and 0.7, respectively) (Table 1). These results suggest that all three of these compounds may show efficacy for treating patients infected with the omicron variant.

:

Additional studies are needed to determine whether these antiviral therapies are indeed effective against infection with the omicron variant.

[bennevisplace in reply to AussieNeil]

Thanks. That's the study I had in mind.

[studebaker]

My daughter will be very happy as she had AZ for first vaccine and Pfizer for second and booster shot. She was a bit concerned at the time, this study will put her mind in peace.Wonder if mixing mRNA vaccine would show the same promise ?

Thank you Neil and Happy Easter 🐣

Dana

[kitchengardener2]

Thank you Neil, I don't understand all the technical data but think I got the gist of it. I have only been offered Pfizer and so far have had four with a 5th due later this month. I wonder if I will be given another Pfizer or if it may be different. When my husband went for his 3rd covid jab, he was given Moderna after having had two Pfizer ones. The doctor said then that it was thought that mixing vaccines might work better. We have taken part in the National Office of Statistics Covid19 Survey since the beginning of the pandemic. We are visited once each month and we give a PCR test and a blood sample to check for antibodies. Right up until my 4th jab my blood sample was negative for antibodies (my husband's has always been positive) but the last three have been inconclusive. Just my assumption maybe but I wonder if after the 4th jab I have developed some antibodies but not enough to register as positive?

[janvog]

I had 3 Pfizer and one Moderna booster and now I get ready for the second booster . Get with it !

[AussieNeil Partner Administrator]

Mix-and-Match COVID Vaccines; Long COVID recovery, Aspirin for Heart Disease Prevention, (with my emphasis)

from: medpagetoday.com/podcasts/h...

TTHealthWatch is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine in Baltimore, and Rick Lange, MD, president of the Texas Tech University Health Sciences Center in El Paso, look at the top medical stories of the week.

Mix and Match COVID Vaccines

Rick: This has really been a topic that I continue to address. "Okay. I need to get a COVID booster. Should I get the same booster as the original vaccine or should I get something different?"

This was a really well done study that involved over 11 million individuals that had been vaccinated in Chile. Most of them had received as their initial vaccine the Sinovac Biotech called CoronaVac. It's an inactivated virus vaccine. Then as their booster, they either got another dose of the Sinovac or they received the AstraZeneca/Oxford vaccine, or they received the Pfizer vaccine.

They compared the outcomes. Did they prevent either symptomatic COVID cases or the COVID-19 outcomes -- such as hospitalization, or admission to the ICU, or death -- both for just the vaccines versus unvaccinated and then for the mixed versus those that matched.

What they found is that of the 11 million individuals who were eligible for this study, over 4 million had completed their primary immunization and they received their booster during that study period. About 45% of them had received the AstraZeneca, about 50% received the Pfizer, and about 5% had received the CoronaVac.

If you received the same booster as you did originally, it's about 80% effective. But if you received a different one, it was closer to about 95% effective. By the way, the numbers are very similar looking at COVID-related hospitalization, ICU admission, or death, in that getting vaccines and booster was clearly much more effective than not getting anything. But if you received a different vaccine, it was even better.

Elizabeth: It makes a lot of sense to me because they all vary slightly and so producing this greater breadth of antibodies just seems like an effective thing to do. I would just note that I did that.

Rick: Many of us have, Elizabeth. This was before the data became available. Unfortunately, many people don't have the option to have a choice. They have to receive what's available. What I would say to our listeners, especially those around the globe, is that the most important thing is to get your primary vaccine and a booster. If you have the opportunity to choose what that booster is, I would mix it rather than match it. But the most important thing is to make sure that people are primarily immunized and boosted.

Disturbing Long COVID recovery statistics after hospitalisation - from UK study

Rick: Well, Elizabeth, the thing that was most surprising to me is that the number of people that reported a full recovery 5 months and 1 year after hospitalization for COVID was 30% or less. The most common symptoms were fatigue, muscle pain, people physically slowing down, poor sleep, and breathlessness. I have to admit the thing that was most striking to me was the fact that it was the minority of individuals that fully recovered and if there wasn't recovery at 5 months, very few of those recovered even at 1 year.

Important: - Update on the use of aspirin for primary cardiovascular prevention

Rick: It's an update from the USPSTF about which patients should take aspirin for primary cardiovascular prevention. These are individuals that don't have known cardiovascular disease, but they may be at risk for it. They may have high blood pressure or diabetes, or other conditions, or just because of their age.

The recommendations now are very different than when they were first established years ago in 1989. The newest recommendations changed in three ways. They are saying individuals over the age of 60 don't need to be started on aspirin in general. Those between the ages of 40 and 60 should be considered if they are at high risk, if there is a 10-year risk of having a heart attack, or a stroke that approaches 20%, and the individuals over the age of 75 should probably stop their aspirin because of the risk of gastrointestinal bleeding.

Neil