Johns Hopkins Transplant Vaccine study

[iolaire]

Johns Hopkins is running a Transplant Vaccine study, to sign up see https://transplantvaccine.org/

They sent an email today to share with you our first wave of findings which has been under publication embargo, but just this morning, they were published in the Journal of the American Medical Association. Here is the link: https://jamanetwork.com/journals/jama/fullarticle/2777685

From a quick read I feel like the following is most important relating to the first dose response:
Transplant recipients receiving anti–metabolite maintenance immunosuppression therapy were less likely to develop an antibody response than those not receiving such immunosuppression therapy (37% vs 63%, respectively; adjusted incidence rate ratio [IRR], 0.22 [95% CI, 0.15-0.34], P < .001; Table). Older transplant recipients were less likely to develop an antibody response (adjusted IRR, 0.83 [95% CI, 0.73-0.93] per 10 years, P = .002). Those who received mRNA-1273 were more likely to develop an antibody response than those receiving BNT162b2 (69% vs 31%, respectively; adjusted IRR, 2.15 [95% CI, 1.29-3.57], P = .003). This association was similar in a sensitivity analysis limited to those tested 14 to 21 days after vaccination (n = 245; adjusted IRR, 2.29 [95% CI, 1.32-3.94], P = .003).

Discussion
In this study of immunogenicity of the first dose of the mRNA SARS-CoV-2 vaccine among solid organ transplant recipients, the majority of participants did not mount appreciable antispike antibody responses. However, younger participants, those not receiving anti–metabolite maintenance immunosuppression, and those who received mRNA-1273 were more likely to develop antibody responses. These results contrast with the robust early immunogenicity observed in mRNA vaccine trials, including 100% antispike seroconversion by day 15 following vaccination with mRNA-12735 and by day 21 following vaccination with BNT162b2.6

mRNA-12735 = Modena
BNT162b2.6 = pfizer-BioNtech

If you have a choice it sounds like Modena vaccinations are more likely to develop antibody responses. 

I'm interested in know which drugs fall under the "anti–metabolite maintenance immunosuppression therapy" category. A few quick google searches don't make it clear.

[MooseMom]

Thanks so much for this information, iolaire.  In doing some quick, not too thorough research, and in looking ONLY at the usual cocktail of immunosuppressants that most of us get, prednisone is a corticosteroid, tacrolimus is a calcineurin inhibitor, but it's mycophenolic acid that is in a class of drugs called "antimetabolite immunosuppressant".  So, that sucks.  But please don't take my word for it as I have not had loads of time to dig any deeper.

I did have the Moderna vaccination, but I wasn't given a choice.  I've had only the first dose with the second due 1st April.

Still, none of this is a surprise.  I have always suspected that if you are actively suppressing your immune system, anything you do to "jump start" it surely must have diminished results.  That's just common sense to me.  That said, I will take anything offered that might increase my chances of surviving covid, even if said chance is smaller than hoped.

Again, thanks for posting this.  Please post more info when/if you receive it.

What are your general thoughts/feelings about this?  I'm rather disappointed, truth be told.

[MooseMom]

"These findings of poor antispike antibody responses in organ transplant recipients after the first dose of mRNA vaccines suggest that such patients may remain at higher early risk for COVID-19 despite vaccination. Deeper immunophenotyping of transplant recipients after vaccination, including characterization of memory B-cell and T-cell responses, will be important in determining vaccination strategies as well as immunologic responses after the second dose."

And what does this actually mean?  What do you all think will be DONE for us as a result of these poor results?  Or, are we just going to be conveniently ignored?

[iolaire]

MooseMom thanks yes that’s Mycophenolic acid. Another person on the Facebook group posted a link that made it clear.

[MooseMom]

MooseMom thanks yes that’s Mycophenolic acid. Another person on the Facebook group posted a link that made it clear.

OK, good.  I didn't want to lead anyone astray.

Upon thinking about all of this a bit more, I'm more than disappointed.  I'm gutted.  I have tried, and mostly succeeded, in holding back my despair for a year now.  That particular dam now has an enormous crack in it.  I don't dare hope that the second dose will be any more promising than the first.  I really don't see anything being done for us.  I think we will be abandoned.

[iolaire]

MooseMom thanks yes that’s Mycophenolic acid. Another person on the Facebook group posted a link that made it clear.

OK, good.  I didn't want to lead anyone astray.

Upon thinking about all of this a bit more, I'm more than disappointed.  I'm gutted.  I have tried, and mostly succeeded, in holding back my despair for a year now.  That particular dam now has an enormous crack in it.  I don't dare hope that the second dose will be any more promising than the first.  I really don't see anything being done for us.  I think we will be abandoned.

Yes its scary, but I don't know if its time to give up all hope (i.e. I hope its not time to give up hope).  Is only at the first dose so we can hope the second does something more.  Additionally we have this study going on so we might learn enough to request a second dose or do something else. We also will benefit as the community spread decreases.

On a side note the LabCorp order for the antibody test was for:
164090 SARS-CoV-2 Semi-Quantitative Total Antibody

I'm personally happy we have a measure of if we are protected.  Also I've been a pessimist regarding "getting back to normal."  I'm expecting that the mask use on my part will be needed when exposed to unknown people for sometime as community spread is ongoing and new variants are in the wild.

[MooseMom]

I fully expected the vaccine not to be as effective for us.  That's just common sense.

I also fully expected to still wear masks and to socially distance after vaccination.  I was prepared for that.

I was not, however, prepared to learn that there was no "appreciable antispike antibody response".  I realize that may change after the second dose, but I don't honestly see why it should.  We'll still be taking the same mycophenolic acid.

The only silver lining here is that they seem to have found the exact agent responsible for the muted/"no-appreciable" response.  I confess that I have not read the "Method" section so don't know exactly how they made this discovery, but I also don't know what any bright spark vaccine maker is going to do with this knowledge.

If the vaccine turns out to be a giant dud for us, I really don't know how I will go about the rest of my life.  Will I ever see my son again?  I haven't seen him since Oct 2019.  I suppose we all will be asking these same questions.

[UkrainianTracksuit]

Thank you so much for sharing this study, iolaire.  Seriously, a world of thanks.

I am not a scientist but the results of this study align with my expectations to sadly tell the truth. Knowing from the beginning it wouldn't be as effective in the immuno-suppressed versus the regular population, it was simply a matter of what degree of antibody spike. I expected "something", or at least a bit of protection, than this dismal result though. If you think about it, we typically receive high dose vaccines (compared to the regular population) to initiate that antibody spike (and some have to be redone) so, what should be different about this, you know?

Perhaps the best scenario is that the normies get vaccinated, get the antibody spikes that denote "success" of a vaccine in those populations, and then it is just up to the at-riskers manage the best we can with what is available, until more studies come out, and more vaccines hit the market. I just don't know. It is as if we are expected to not have lives or something. I know that mycophenolate sodium isn't leaving anytime soon and this is completely out of my hands.

I was supposed to have a meeting with the tx team about the vaccine (my GP requested I do it), but now I am like, why bother? 

At least I know Moderna is the way to go IF I have a choice. But then... am I even allowed a choice or will I be labelled one of those "vaccine shoppers" who should "take what they can get"? Will this even be acknowledged as beneficial information if I do push for a particular kind? Now I just have more questions and related neuroses...

[iolaire]

I was supposed to have a meeting with the tx team about the vaccine (my GP requested I do it), but now I am like, why bother? 

Still get in line to receive it and be proud of picking and choosing if you have a choice.  On the Facebook one person says they see better response after the second shot, where another says he talked to his transplant team with numerous people in the study and they said it doesn't look good but he was told age has a big factor.  There are all kinds of unknows.  For example we know the vaccine doesn't always prevent infection but some studies show that infection in vaccinated populations result in less significant effects. 

[MooseMom]

How quickly do you all suppose this information is picked up by transplant clinics? 

Yes, we've been told that the vaccine isn't necessarily expected to prevent covid infection but rather, to reduce the need for hospitalization or services of a morgue.  But can we tx people hope for even that much?

Is there any research going into what the next step should be?  A third dose?

I don't trust other people enough to provide me with immunity via the herd, but I suppose I'm going to have to hope they will care enough.  But they'll just tell us to stay indoors and permanently shield.

You Tea, let us know what your tx team has to say.  And I agree with iolaire; if the Moderna vaccine gives you even the slightest increase in protection, you shop for it.  It's no one else's business, and you owe an explanation to no one besides your medical team.

[kristina]

... Here we also have quite a lot of information available about all sorts of different vaccinations plus reports of many different reactions to particular vaccinations etc., all there ready to make anyone feel extremely insecure and nervous about "it"...  but perhaps each individual reaction might be really dependant on the fitness, body-size, general health, health-history etc. of each participant ? What do you think? 

[MooseMom]

Kristina, the Johns Hopkins study to which iolaire is referring doesn't look at the safety of the vaccine, rather, it looks at the efficacy of it in transplant patients.  This is the study we've all been waiting to read.  Basically, the conclusion is that for transplant patients who are taking the immunosuppressant mycophenolic acid (Myfortic) or any other immunosuppressant in this drug group (antimetabolic immunosuppressant), after the first dose of the mRNA vaccine, there seems to be no real measurable antibody response.  That may change after the second dose. 

This study was published just today, so we are all still digesting it.  It doesn't look like the vaccine protects us much at all, IF at all, at least not after the first dose.  It's very disappointing.

[UkrainianTracksuit]

Still get in line to receive it and be proud of picking and choosing if you have a choice.  On the Facebook one person says they see better response after the second shot, where another says he talked to his transplant team with numerous people in the study and they said it doesn't look good but he was told age has a big factor.  There are all kinds of unknows.  For example we know the vaccine doesn't always prevent infection but some studies show that infection in vaccinated populations result in less significant effects.

Once the vaccination initiative opens up to high risk under-65's (new guidelines have been released by the government and have transplant recipients at the top of Phase 2; so between April to July), I will get in line. See what happens next, right?

Perhaps by then new data will come out in regard to the second shot. As well, it seems Moderna is already looking at the immunogenicity (new word for me today) of the "next generation" of its vaccine as well as boosters. Not exactly great news right now, but it is still something. Not related to tx patients at all but still: https://www.cbc.ca/news/health/moderna-testing-covid-vaccine-1.5950322

You Tea, let us know what your tx team has to say.  And I agree with iolaire; if the Moderna vaccine gives you even the slightest increase in protection, you shop for it.  It's no one else's business, and you owe an explanation to no one besides your medical team.

Definitely, I will let you know. The appointment is in two weeks and hopefully it is not cancelled.  Still, I am sure I can arrange a telephone call in its place to really sort it out.

You do raise a great point as well - how quickly will this data be picked up by transplant clinics? I'd like to know.  This is considerably big news so I hope soon.

Ugh, this is just an emotionally defeating day. Bad hair appointment, this news, Ontario Hospital Assoc. announcement that we're in a third wave, appointments in the air, life becoming a chronic dumpster fire too large to escape or make plans to move ahead. I know I'm not the only one (as expressed here!) but ugh.

[MooseMom]

Yeah, it's been a crap day, right?  I have had only one haircut in the past year.  The last time my hair was this long was when I was in high school.  Not a good look.

I'd been enjoying the past couple of spring like days and have been out gardening.  Today it snowed.  Crap day.

Europe is in a third wave, so I'm not surprised that Canada might be, too.  It's only a matter of time before the US sees the same.  Crap crosses the pond.

I learned two new crap words today, "antimetabolic" and "immunogenicity".  Wish I didn't have to know that.

I'm going to bed, ready for this day to end.

[enginist]

How often do transplant patients receive steroid injections or pills?  And what is the size of the dose, compared, say, to a cortisone shot in the wrist for a mild case of osteo?  The wrist shot, given every three months, is a small, localized dose, but I'm guessing that transplant patients receive larger and more frequent doses.  Is this correct?

In any case, I sympathize with the quandry you are in.  But don't despair too soon.  The second shot may provide adequate protection. 

[kristina]

Kristina, the Johns Hopkins study to which iolaire is referring doesn't look at the safety of the vaccine, rather, it looks at the efficacy of it in transplant patients.  This is the study we've all been waiting to read.  Basically, the conclusion is that for transplant patients who are taking the immunosuppressant mycophenolic acid (Myfortic) or any other immunosuppressant in this drug group (antimetabolic immunosuppressant), after the first dose of the mRNA vaccine, there seems to be no real measurable antibody response.  That may change after the second dose. 

This study was published just today, so we are all still digesting it.  It doesn't look like the vaccine protects us much at all, IF at all, at least not after the first dose.  It's very disappointing.

Many thanks about the information MooseMom, it is very much appreciated and I do stand corrected ... and hopefully the second "shot" of vaccination protects us a bit better? Fingers crossed ! I was told that my first "Pfizer"-vaccination protects me up to 80% and hopefully my second vaccination-"shot", which should "come along" next months protects a bit better and hopefully the side-effects are not too bad ...

Many thanks again for your kind input and I do hope you feel a little better today? Please take care and I send you my best wishes from Kristina.

 

How often do transplant patients receive steroid injections or pills?  And what is the size of the dose, compared, say, to a cortisone shot in the wrist for a mild case of osteo?  The wrist shot, given every three months, is a small, localized dose, but I'm guessing that transplant patients receive larger and more frequent doses.  Is this correct?

In any case, I sympathize with the quandry you are in.  But don't despair too soon.  The second shot may provide adequate protection. 

Hello enginist,
I have not been prescribed or given any cortico-steroids after being diagnosed with a severe allergy to "them", which came about during a hospital-stay ... and ... I have also heard that cortico-steroids can eventually cause problems with bone-density in some people ...
Take great care and I also send you my best wishes from Kristina.

[UkrainianTracksuit]

How often do transplant patients receive steroid injections or pills?  And what is the size of the dose, compared, say, to a cortisone shot in the wrist for a mild case of osteo?  The wrist shot, given every three months, is a small, localized dose, but I'm guessing that transplant patients receive larger and more frequent doses.  Is this correct?

In any case, I sympathize with the quandry you are in.  But don't despair too soon.  The second shot may provide adequate protection.

So, I can't really speak for those taking steroids as regular post-tx maintenance, as I am on a steroid-free regimen. They were discontinued 6 months after transplant.

Immediately after transplant, patients receive high doses of steroids, but they are slowly tapered down. Typically (at least what I experienced in the early days and what I hear from others) it is a maintenance dose of 5 mg of prednisone per day. Unless there is a rejection issue, where IV steroids are administered, there are no injections.

Hope others will chime in with some better info.

MooseMom, all I can do is send a virtual hug.  Perhaps if we spell crap with a K it will seem more fashionable and funner. Like Krap Day Klub.. KDK. "Going to my KDK meeting, ciao!"

[iolaire]

Typically (at least what I experienced in the early days and what I hear from others) it is a maintenance dose of 5 mg of prednisone per day.

I'm at 5 mg and talked to my doctor about it last year.  He made some comment that people still on prednisone fare better transplant wise.  I do have weakening of the bones as seen on DexaScans and have had that since the 1990's when my lupus was active and I was on high doses of prednisone.

FYI I should get my second antibody test for this study on the 25th before my second shot and will have the results in a day or so.

[MooseMom]

Enginist, UT is correct in that generally, immediately post tx, a larger dose of prednisone is given (in my case, 30m daily) and is fairly quickly tapered down to a low maintenance dose (in my case, 5mg daily).  That's quite a small dose in the grand scheme of things.  I take a 5mg tablet in the morning.

kristina, the published study indicates that what you were told about the first dose giving you 80% protection may be incorrect.  It may be true for the healthy general population on which these trials were conducted, but transplant patients were not included in these trials, so no one had any way of knowing enough to make that claim to you.  That said, we do not know yet if an immune response will be coaxed out of a tx patient's immune system after the second dose.  Maybe that second dose does the trick.  I am assuming there will be follow up trial studies done after the people who are included in the trial receive their second dose.

But I want to make clear that for purposes of this discussion, the report that iolaire so kindly shared with us indicates that steroids are not the problem here.  The immunosuppressant most tx patients take, mycophenolic acid or another drug in that class, seems to be the medication that thwarts an antibody response from the Pfizer and Moderna vaccines.  If you are on a steroid free protocol but still take mycophenolic acid, the results of this study indicate that you will have very little protection from the vaccine after the first dose.

If I have misunderstood something, please let me know.

KDK

[MooseMom]

Typically (at least what I experienced in the early days and what I hear from others) it is a maintenance dose of 5 mg of prednisone per day.

I'm at 5 mg and talked to my doctor about it last year.  He made some comment that people still on prednisone fare better transplant wise.  I do have weakening of the bones as seen on DexaScans and have had that since the 1990's when my lupus was active and I was on high doses of prednisone.

FYI I should get my second antibody test for this study on the 25th before my second shot and will have the results in a day or so.

iolaire, I've had the same conversation with my own tx neph about pred, and she said the same thing.  I have not had problems with prednisone, so I'm fine with it.  I am very aware of the possibility of weakening of the bones due to long term pred use, not to mention my age and gender, and I get a DexaScan every other year.  After almost 9 years, my bones are still ok.

I am extraordinarily curious to hear your antibody test results.  I'll put that date in my diary.

[UkrainianTracksuit]

I'm at 5 mg and talked to my doctor about it last year.  He made some comment that people still on prednisone fare better transplant wise.  I do have weakening of the bones as seen on DexaScans and have had that since the 1990's when my lupus was active and I was on high doses of prednisone.

FYI I should get my second antibody test for this study on the 25th before my second shot and will have the results in a day or so.

In regard to the antibody test, likewise, I am interested to learn the results after the second shot. It is almost like a fingers crossed moment. Definitely will add to the puzzle or help the general community make more sense on the matter.

Now, about the prednisone.. not that I want to turn this into a prednisone thing rather than mycophenolate-focused .. the doctor info that you and MooseMom have shared is what I've learned from reading studies as well. Graft survival seems better on prednisone. Naturally, I had an existential crisis when I read this and questioned my doctor's decisions (not directly, as he is not the sort one questions, very highly regarded though). My local neph shared with me that only the SPK recipients (with the same doctor) are prednisone free versus the ones he "sent on their way" with a single kidney transplant. They take prednisone. Anyway, local doc said it is because of the side effect of steroid-induced diabetes. I hope that's right.

It's still a KDK feel today! Still feeling disheartened about the vaccine, and then I had to encounter anti-vaxxers/corona-denier comments on a hospital social media page. Just ugh. Not even in the mood to laugh at low quality diamonds on television shopping...

[MooseMom]

UT, it makes a lot of sense that SPK recipients might be on a different anti-rejection drug regimen than renal tx patients.  I am no cheerleader for prednisone, nor am I an "anti-predder".  It just is what it is.

Developing diabetes while taking the anti-rejection cocktail is certainly a concern.  I have a glucose test run each time I have my regular labs done, and so far, so good.  Each of the drugs I take can cause T2D in the long run, it seems.  Ugh.  KDK.

Since this disappointing news from JAMA, I am REALLY not in the mood to even listen to anti-vaxxers or covid deniers.  They don't know how lucky they are.

[MooseMom]

Here's a summary of the Johns Hopkins results laid out in normal human language.

https://apnews.com/article/organ-transplants-coronavirus-pandemic-e6a3ad119cabf5cd8561ef23f1105448

KDK!!

[enginist]

I am just a peripheral member of the Krappy Kidney Klub, but I very much appreciate the dissemination of this information.

I don't know if it adds anything, but I've learned that antimetabolites interfere with RNA synthesis, which is exactly how the Moderna and Pfizer vaccines work, as implied in the name ModeRNA.  Maybe the J&J vaccine would be worth pursuing, if anyone has that luxury.

[MooseMom]

I am just a peripheral member of the Krappy Kidney Klub, but I very much appreciate the dissemination of this information.

Oh, anyone can join.  We've not snobs.

Have any of you had the two dose Shingrix vaccine to protect against shingles?  I had both doses, and each time I got a very sore, red arm along with that "I don't feel so great" sensation the next day.  In just about all discussions about possible side effects from the covid vaccine, you hear people say that if you have more unpleasant side effects than just a sore arm, that surely must mean that your immune system is working as it should.  I don't know if that true or just waffle, but that sentiment is out there.

So, this is making me wonder if the side effects I felt from the Shingrix shots (but not from the Moderna covid shot) means that my immune system mounted the desired antibody response.  But I don't know because I was never tested for antibodies.  It was just assumed, I suppose.  Do any of you have any information about this?  Did any of you who took the two Shingrix shots ever have an antibody test afterwards?

I mention this because it made me wonder if we are indeed protected against shingles by the shingrix shot which uses "inactivated virus", then could a covid vaccine using "inactivated virus" be made for us?  I realize it would take much more time, but it seems logical, assuming that the Shingrix vaccine conveyed any protection at all (and I'm betting no one thought to find out).

What do you all think?