Friday, August 12, 2022

New Study: Moderna VS. Pfizer Vs. Novavax vs. Johnson & Johnson vs. COVID Infection

welcome to another medcram covet 19 update so this is probably the study that a lot of us have been looking forward to ever since the pandemic and these vaccines have come out imagine if you could test the immune system and its reaction to the modern vaccine the pfizer vaccine the jansen.

Pharmaceutical vaccine and the novovax vaccine in the same population at the same time using tests on the same platform in the same lab so you can eliminate all of those variables and actually compare what effects these vaccines have on the immune system and then not only that but after six months be able to compare that to.

The effect of the natural infection of sars cov2 in the same population at six months well this is exactly what dr weiskopf and dr crotty at the la jolla institute for immunology have done teaming up with dr seti who's also faculty at the university of california san diego and so what i want to do is go over the results of this study and this.

Is just now in publication in the prestigious journal cell titled humoral and cellular immune memory to 4 coven 19 vaccines and for those of you who want to cut to the chase at least we can take a look at this we are looking at the modern vaccine here in red we're looking at the pfizer vaccine here in blue we're.

Looking at the jansen or the johnson johnson pharmaceutical vaccine here in green and yes novo vax novovax vaccine here in purple and then of course the stars kovi 2 infected people which we'll talk about more in details here in yellow and at six months of immunity six months after this initial vaccination and or.

Infection if you look at binding immunoglobulins you can see the profile here with this dotted line being the lower limit of quantification if we're looking at neutralization of a pseudo virus of stars kov2 you can see here the profile among those and here with cd4 with the circulating t follicular helper cells you can see that here as well cd8.

And then of course the all-important memory b cells and the profile that is seen six months after either vaccination or infection with sars cov2 now remember that this was done in san diego and so they did not have access to people who are vaccinated with the astrazeneca vaccine for instance or cynopharm or sputnik so these are ones.

That are specifically authorized for use in the united states so stick with us and let's get into the details of this study which i think are really interesting and of course we'll put a link in the description below to this article so you can read it for yourself so again what they did in this study was.

They looked at 30 people who had the modern vaccine 30 people who had the pfizer biontec vaccine 30 people that had the jansen vaccine and 12 in this case that had the novovax we'll talk more about exactly that as you can see the female to male ratio in all of these groups was about the same a little bit more equitable in the novovax vaccine.

And also slightly younger age group in that novovax vaccine group in terms of race or ethnicity they tried to keep that also pretty similar across the spectrum what's really important to understand is the exclusions as well anybody with neutralizing antibodies or nucleocapsid antibodies which would signal that the.

Patient has been infected previously with starch covi2 or excluded from the study they wanted people who had never been exposed before to either the virus or the vaccine also to that degree because it's not obvious sometimes if you've been infected if they had any peaking of the immune results after the first dose this is usually a sign that.

There's been a previous infection that you're getting hybrid immunity those people were also excluded from the analysis and of course if anyone went on and got a third shot or a second shot in the case of the jansen pharmaceutical vaccine they were excluded from the study so they're just looking at people with two shots for the mrna vaccine one.

Shot with the jansen pharmaceutical and two shots with the novovax the point of this again is to look at the different platforms obviously the moderna and the pfizer vaccines are both mrna vaccines and remember what that means that means that an mrna molecule goes into the cell of the human body just like it does in the natural.

Infection and that causes the ribosomes to make the spike protein which then causes the immune response that is as opposed to the johnson johnson or the jansen pharmaceutical vaccine which is an andenovirus vector which infects the cell and actually has a dna molecule which is then transcribed into messenger rna and then finally into the spike.

Protein so that's a little bit of a different platform and then of course the novovax which is a more traditional type of vaccine where it's simply the protein that gets injected into the body and that makes the immune response so interesting to look at these three types of platforms and see how they are different.

Again we're not here trying to say which vaccine is better because remember that vaccines not only have benefits on the benefit side but they also have risks on the side effect side and so this is not addressing any of the issues with side effects or risks this is coming out of an immunologist's laboratory which is looking at the effects on the immune.

System and so obviously we're going to get a lot of good data on that aspect just keep in mind that for instance while the mrna vaccines have a low incidence of myocarditis you wouldn't necessarily see that in the johnson and johnson and conversely as we all remember a number of years ago when we first started that the campaign for.

Vaccination for the johnson and johnson vaccine had to be paused because of a concern for blood clots which were not seen in the mrna so the point of all this is that we're looking at one aspect here we're looking at the benefits we're looking at the efficacy of vaccines and their ability to protect against infection and also disease in stars kovi.

Too so we've showed you how they came about getting subjects for the vaccination in the four different groups the next question is how do they get the subjects in terms of comparison for sars kovi to infection that comes from another research article that was published by the same group as.

You can see out of the same la jolla institute for immunology it was published in 2021 they received and were able to get the data specifically six months after infection and here's a quote from that article specifically talking about that cohort that's going to be looked at in this particular current paper and they say quote all of.

The convalescent donors experience mild illness defined as patients with a sars cov2 positive test who have never been hospitalized seropositivity against sars cov2 was confirmed by enzyme-linked immunosorbent assay or elisa as described below at the time of enrollment all covet 19 convalescent donors provided informed consent to.

Participate in the present and future studies so in the current research that we're going to look at we are going to be looking at different points along the way when these subjects got their vaccine that's not going to be the situation when we're looking at these patients in the study that got coveted.

19. we're only looking at a snapshot in time at six months and that's going to be important to understand because when we throw up these numbers and graphs in this current study anytime we're comparing them to people who have had covet 19 through stars cov2 it's going to be a snapshot at around six months which of course is important because we.

Want to know how much immunity do subjects have at six months so i just want you to be aware of that so let's take a look now at our vaccine subjects and so what you can see here is we've got the moderna vaccine here in red again pfizer in blue jansen in green and novavax in purple the time periods that we're going to be looking at for.

Instance this is going to be t1 this is going to be t2 this is going to be t3 this is going to be t4 and this is going to be t5 and all of the data that we're going to get at t1 is going to be prior to vaccination that's what the blood was like right before the first dose and so t1 in all of these first three are going to be baseline examinations and as we go.

Through t2 t3 t4 t5 and this is around six months and this is where we are going to be using these data points here to compare against the stars cov2 infections you may notice something here we have t1 through t5 for the moderna for the pfizer and for the johnson and johnson or the jansen pharmaceutical vaccines but we do not have it for the.

Novavax and that's important to understand why that's the case the reason why this is the case now listen very carefully is because when they did the novovax randomized trials the phase three trials they did not want to leave people out they wanted to make sure that every single one of them was vaccinated eventually and so what they had to do.

Was they had to do two sets of two vaccinations people were randomized so that the first series was the placebo and the second series was the actual vaccination and the second randomization was that the first dose was the vaccination and the second was the placebo and so because of that we can only look at t4 and t5.

Knowing that this is what things looked like after vaccination at six months so now realize they did not receive any doses here they only receive placebos as it's mentioned here and so as a result of that we could not be drawing blood here and here in those patients because we wouldn't be able to keep them blinded.

Because then they would know what group they were in so as it turns out what we can only look at in the novavax is t4 and t5 and this is a figure from the article that simply just codifies what i was just saying here in graphic format so let's look at the data and the first sets of data here that we're looking at.

Is specifically the spike igg so this is the antibody that's circulating around in the body that is going to bind to the igg and just the point here of note is that the virus that we're looking at here is very early on in the pandemic we're not looking at variants we're not looking at the delta variant or the alpha or even omicron we are looking at.

The native virus so a lot of this may not be applicable to today in terms of the omicron variant but what this does give us information on specifically is how these different platforms whether it's an mrna directed vaccine whether it's an adenovirus vector or whether it's a traditional protein platform vaccination how do they affect the.

Immune system in a way that protects against sars-cov2 so again we're looking at antibodies against the entire spike protein this is an igg which means it usually hangs around the other thing that i want you to notice here is the scale is not linear it is logarithmic and so at any data point the number of hash marks that you cross is the number.

Fold of difference so if you cross two hash marks that's twice the level between 10 to the 2 and 10 to the 3 that's 10 spikes so that's 10 fold increase and so what you can see here is that baseline which is very low here for the moderna vaccine we had a very high rise here in the titer of anti-spike igg and then at around t3 there is a pretty.

Precipitous decline this doesn't look like a precipitous decline again because it's logarithmic but if you notice here we are crossing at least three to four hash marks which means that is a three to four fold drop in the levels of antibodies that we're seeing here but also notice across the board that the mrna vaccine specifically the modernity.

And the pfizer vaccines had the highest titers the johnson johnson did not see very high titers but you can see that it was actually pretty consistent across the board with the novovax this is the traditional protein type of platform for vaccination there was an increase here at t4 so again we're going to compare it.

To all of these t4s but there was still a decline even after some period of time although it was a decline numerically but it was not statistically significant now what we're seeing here on the right hand side is what's going on at six months this is with just two shots for the mrna.

And just one shot for the johnson and johnson and so again in red we have moderna in blue we have pfizer green is janssen the purple is novovax and here yellow is the infected sarskov2 cohort that we talked about previously and i think that the key here to understand is that for the most part there was circulating antibodies in all.

Of these groups in all of these graphs this dotted line here represents the lower limit of quantification of the assay and so there was one individual in that cohort in the novovax cohort that had undetectable anti-spike igg antibodies and if you want to look at the means you can see here how it was different across the.

Board and again remember each one of these hash marks is a fold increase or decrease depending on the direction that you're going so now what we're going to do is we're going to look at the receptor binding domain which is a very specific portion of the spike protein it's the very tip if you will and what you see here is.

Things that are very very similar that we saw before again here we look at the lower limit of quantification and here we have two individuals that went below that and another two in the infected group that went below that as well this kind of goes along with what i've heard dr crotty mentioned before in terms of vaccination versus infection.

And that is that vaccination typically gives a more consistent response whereas infection may not be so consistent and again remember with this cohort none of these people went to the hospital all of them had mild covet 19 so we don't know what the response would be in those that were sick enough to be hospitalized and if we look here we can see that the.

Johnson and johnson cohort again pretty tight but also the mean was almost an order of magnitude lower in terms of receptor binding domain igg antibodies okay what we're looking at here is pseudo virus neutralization this is a universal type of test that we do all over the world that checks to see what the antibody titers are in a person's.

Serum that can neutralize a viral particle that's coated with the stars kobe 2 spike protein that is also very interesting to look at here you can see moderna very high titers which are good and here you can see the pfizer the johnson and johnson jansen pharmaceutical vaccine is not as high although we do see pretty high.

Titers here with the novovax and again you can see here in terms of the pseudo virus neutralization tighter what the results were and you can see the difference here between moderna and the sars cov2 infection was very highly statistically significant in terms of neutralization tighter you can also see that there is a larger splay in terms of.

Response in the natural infection for those that had mild infection it's even larger here in the novovax vaccine again with two individuals that were below the lower limit of quantification so all this caused the authors to write in their results section that antibody titers at six months were compared to sars kovi ii infected subjects who were.

Enrolled for a previously reported study the previously infected individuals were selected randomly recipients of the mrna vaccine so that's both the modern and pfizer had a 4.5 fold higher spike igg a 6.4 fold higher rbd igg and a 3.4 fold higher neutralizing antibody titers compared to previously infected subjects antibody titers from novovax recipients.

Also trended higher than sars kovi 2 infected subjects antibody titers from the johnson and johnson were similar to titus from sars kobe 2 infected subjects okay so that's interesting to know in terms of antibodies but we all know and we've all learned here very well over the last couple of years that immunity and the way you stay out of the hospital.

Is more than just antibody response you also need to look at t cells and memory b cells so let's take a look at that now so here we're looking at something called spike specific cd4 t cell percents they had different assays that they used at la jolla one of them was this aim plus assay but there are other assays that they use that i'm not.

Showing because they have the same results but feel free to look up the paper and see those other assays this is very representative of what we saw again we're looking at a logarithmic scale it's important for you to understand that and you can see here that it's very important this is something that they were looking at very early in the.

Pandemic is whether or not these vaccines were able to elicit a t cell response because if you can elicit a t cell response then that means you can get much further and much more robust cell-mediated immunity and you can see here that we had a very good robust response with moderna also with the pfizer vaccine and really also with the.

Johnson johnson vaccine as well and very happily with novovax so novovax had a very good t-cell cd4 response as well in fact arguably it had one of the highest in terms of after six months again we're looking here at six months what is the t cell response what is the cd4 t cell response after six months and we've got moderna we have pfizer we have.

Johnson and johnson we have novavax which actually had a very tight and elevated response in terms of cd4 t cells all in comparison with those that were again naturally infected with sars cov2 but did not have to go to the hospital in the study they looked at spike specific cd8 positive t cells although.

They did not do a comparison that i could find to those that were naturally infected you can see here robust responses pretty much all across the board however what was interesting is at the t4 period of time it was unclear why that was such a low response in that situation but at t5 there was an increase above.

The lower limit of quantification so a lot of time and effort has gone into looking at something called memory b cells that's really important this we're specifically looking at the receptor binding domain which is where the sars cov2 virus binds to the ac2 receptor and in all of these cases here you can see from t4 to t5 all the way.

Across that there was a robust response which is good it means that at least in terms of mounting a response down the road if someone becomes infected again and again that there's going to be a response that keeps people out of the hospital with cellulated immunity if we compare those again with the vaccine cohorts and those that were.

Infected with sars cov2 we can see that generally speaking all of these are good responses again these are at six months and if you wanted a better look at that again we're looking at spike memory b cells and we're looking at a logarithmic scale and so any kind of deviation here is a full difference.

And so the authors of this study state that the longitudinal analysis of t cell b cell and antibody response to four different covate19 vaccines in humans representing three different vaccine technologies identifies different quantities and quality of cd4 positive t cell cd8 positive t cell and antibody response elicited by the moderna vaccine.

The pfizer vaccine the jansen vaccine and the novovax vaccine antibody levels decline but memory t cells and b cells were comparatively stable so in terms of limitations of the study they say here that they did not evaluate the recognition of variants they also did not test as we mentioned astrazeneca coronavac cyanofarm and.

Sputnik because those were not available in the united states in terms of funding for the project it came from the national institute of allergy and infectious diseases the national institutes of health and the department of health and human services and you can also see the declaration of interest as well.

Again we'll put the link to the article in the description below and also join us at medcram.com for over 60 hours of continuing medical education and review of medical topics thanks for joining us you.

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