Moderna Vaccine Significantly More Effective Against Delta Variant Than Pfizer | Hacker News Reader

Moderna Vaccine Significantly More Effective Against Delta Variant Than Pfizer

medrxiv.org

113 pointsmitchbob92 comments

Moderna estimated to have half the risk of break through infection by delta variant.

Moderna and Pfizer both have comparable (low) risk of hospitalization and death when infected with delta variant.

Primary difference vaccines is dosage (Moderna had a bit over 3x amount of material per shot) and maybe scheduling (Pfizer was scheduled for 21 days between shots, Moderna for 28 - though given how shots were actually administered in reality, this is probably a wash).

Study design has many limitations, but is probably reasonably generalizable.

As a Canadian with combo Pfizer+Moderna, I am personally curious what my risk profile would look like. I wonder if a similar study on Canadian data could be useful - an intermediate risk profile for the combo shot would sure be persuasive evidence.

Edit: Removed ambiguity in second sentence.

> Moderna and Pfizer both have comparable (low) risk of hospitalization and death.

This is still probably the most important overall point.

Wait, was your combo shot one of each? or two of each? I've been curious to learn more about getting both (already had two Pfizer) but resources on the matter are hard to find

Some Canadian provinces treated mRNA vaccines as interchangeable. In Ontario a lot of people got a first dose of Pfizer and a second of Moderna.

There's currently a study underway in the UK (I forget the name, but it run by the University of Oxford) to assess the efficacy of mixed-dose vaccination.

More than mRNA vaccines as interchangeable, we (Ontario) mostly treated the oxford vaccine as interchangeable with the mRNA vaccines too, until we started giving it to less people.

Not gp, but I'm also a Canadian with the covid-cocktail. I got my Pfizer back in May, and then my Moderna at the beginning of July.

Some of the older (55+) crowd got a different mixture, with AstraZeneca shots in the early spring and Pfizer early summer.

Say what you will about our weird combos, but we have a very high number of people immunized now, so it seems to be working...

Same here in Canada. I got Pfizer through public health followed by Moderna 8 weeks later at a walk in pharmacy.

Many Canadian provinces did a Moderna/Pfizer combo (one shot of each) to address shortages and get more people fully vaccinated faster.

It sounds like they were really following the science, and trying some new stuff along the way.

Yes, you should have seen how much complaining it generated!

I’m Canadian and had one shot of AZ as a first dose. Followed by one shot of Moderna maybe 10 or 11 weeks after the first does of AZ.

The best combo so far (June) was AstraZeneca first then Pfizer (not the opposite, nothing then about Moderna), the next good one will be probably intranasal AstraZeneca after some mRNA:

Mixed Oxford/Pfizer vaccine schedules generate robust immune response against COVID-19, finds Oxford-led study: https://www.ox.ac.uk/news/2021-06-28-mixed-oxfordpfizer-vacc... ,

.. https://science.sciencemag.org/content/373/6553/397 - "the ideal vaccination strategy may use an intramuscular vaccine to elicit a long-lived systemic IgG response and a broad repertoire of central memory B and T cells, followed by an intranasal booster that recruits memory B and T cells to the nasal passages and further guides their differentiation toward mucosal protection, including IgA secretion and tissue-resident memory cells in the respiratory tract." .. (https://news.ycombinator.com/item?id=28019151),

https://news.ycombinator.com/item?id=28016821 - Covid-19 Vaccine Intranasal Study (COV008), UK phase 1 trial recruiting,

That said, current vaccines don't provoke the exact same response as an actual infection, particularly in that they don't fully stimulate an immune response in the mucous membranes of the upper repository tract. Here's an Scientific American round-up article (from back in March): https://www.scientificamerican.com/article/to-beat-covid-we-...

[..]

The current vaccines are excellent at helping the body stop the virus as it progresses into the lungs and further (thus the massive reduction in severe illness and deaths). But it still means that there's a period of a few days after initial infection when a vaccinated person has a relatively naive immune response (while the virus is mostly just in the nose/throat). This would then result in the person still being pretty contagious. (https://news.ycombinator.com/item?id=28014448).

I would like to see intranasal Novavax (intranasal mRNA is more difficult ?), having good results, as an option to this mix..

> Moderna and Pfizer both have comparable (low) risk of hospitalization and death.

You mean if you then get the delta variant? Or low risk of hospitalization and death by simply getting the shot?

I'd assume the former.

I intended to mean about the hospitalization and death risk of the delta variant while vaccinated.

The other thing you allude to is the timing. I'm in Canada too, and got my shots 8 weeks apart which was the earliest possible due to availability. For people that got their first shot early, I think the delay is even longer. And now I believe it's back to the manufacturer recommendations.

I understood there are studies that say a longer delay may be better, so I'd be curious too how the result here translates to people who had a much longer time between shots. Was the UK also in this situation?

Your comment is a bit ambiguous, suggest rewording the second sentence to indicate that you mean through infection rather than through the vaccination itself.

It seems a risky proposition without sufficient evidence for safety and efficacy.

https://globalnews.ca/news/8021692/mixing-covid-19-vaccines-...

What test is used to distinguish between the original virus and the delta variant?

In this study, they did not directly do that. Instead they extrapolated from the population/state level delta prevalence estimates (so whatever the state was doing to do that.. probably sequencing) over different time intervals.

My understanding was that moderna had 3x more active vaccine ingredients and lower cold chain requirements, while Pfizer also needed to be mixed / prepared before injection.

It seems like Pfizer had more opportunties go wrong especially when rollout was outside of hospital settings and at population scale. My understanding was initially Pfizer was limited to hospitals in Canada, but ended up in pharmacies and other temporary sites.

I have seen Pfizer girl videos, so I am glad I got Moderna. Nobody can convince me Pfizer doesn't cause mental damage.

To be fair, you would have a low chance without any vaccinations as well. I think in the lower age brackets the risk reduction was < 10%, which is perhaps even in the range of statistical fluctuations even with large sample groups.

At least the data I saw last, cannot find it currently.

This does mesh with the data out of Israel showing a reduced efficacy in the Pfizer vaccine against Delta. That data was considered an outlier (there were also some specific criticisms that I have since forgotten), but now perhaps that study will be taken more seriously. Israel's solution was to approve a third shot for high risk individuals. Approvals for third shots should be happening in the US very soon too.

If Pfizer wore off in 6-8 months what does it say about the next year? A big chunk of the population would have lost a sizable chunk of immunity no? Are we really confident that global vaccination would be high at that point? I really wish US ordered, manufactured and donated a ton more to quash this thing

It did not so much wear off as that it simply doesn't protect as well against this new strain. It most likely still protects just fine against the alpha variant but that one has now been all but displaced.

Crazy that we can see the pure savagery of evolution right in front of us

The rate at which viruses reproduce is what allows you to see this, every biology freshman probably does the e-coli + arsenic experiment, it's a real eye opener as to how slow walking a treatment can actually create a resistant strain.

Is it wearing off or just reduced efficacy to begin with? My understanding is that dosing between the vaccines were all different

My understanding is that this is more about generating a robust immune response in the first place than about losing protection over time. There have been a lot of studies looking at third shots, at natural immunity combined with vaccines, and even at mixing vaccines. And the general idea is that there are ways to generate a more optimal immune response, and the vaccine courses given emergency authorization are probably not the best of all options.

Researchers have yet to determine how long natural immunity lasts, and it may last for a very long time. Immunity from vaccines is expected to be at least as durable as natural immunity, though some studies have shown a slight decline in protection over months. But there are definitely no clear signs yet that an annual shot will be necessary.

Ah got it. I didn’t catch the nuance that the efficacy drop is specific to delta. I wrongly assumed that it was for all variants. Thanks!

I saw an interesting point (I think it was a scientist quoted in the NYT) that said once a vaccine out in the general public, it gets incredibly hard to get good efficacy numbers, because there are so many things that correlate with vaccine status—age, wealth, risk level, attitude towards COVID, geographical area—that also can affect risk of being infected/hospitalized.

The specific criticism, that even the original author accepted later, was, that the growth of the infections in Israel during the study where focused in cities with lower vaccination rates compared to the whole of Israel. I.e. the effectiveness of the vaccine was underestimated in the study. Additionally, you have to consider that Israel got the vaccine very early, i.e. more people had their shots a longer time ago.

Meanwhile, Biontech (the developer of the Pfizer vaccine) applied in Europe for approval to administer third shots 6 to 8 month after the second shot. It remains to be seen, whether the higher concentrated Moderna shots will need a third one a bit later.

One has to be very careful to properly separate a lot of different aspects for drawing general conclusions, regarding this pandemic.

And Novavax was just found to be 90% effective across a range of variants. Too bad they didn't have a big partner to speed their trials along.

I was really hopeful for Novavax. But recent news about manufacturing woes and US pulling funding is disappointing.

The preliminary results looked great. Combined with low rate of side-effects and higher storage temp (2-8 C), it could have been a good 2nd (or 3rd) choice for the developing world.

https://www.nih.gov/news-events/news-releases/us-clinical-tr...

I would have loved a protein based option. I think there haven't been enough questions around the mRNA vaccine longterm potential impact. There are woefully few studies exploring the potential for autoimmune conditions. I find this especially troubling when using ones own cells to develop the spike protein. Normally the immune system codes off multiple proteins of the cell, but this would be a problem when the other cell proteins are legitimate.

Basically, there are still more questions than answers in my mind. I just hope the national countermeasure compensation fund will be able to handle any potential fallout.

Keep in mind, every single cold and flu you've ever had has used the same mRNA pathway to duplicate itself. Anyone reading this has had this happen in their body literally billions of times and will have it happen billions more. Is it just the single-protein aspect of it (compared to a full virus) that bothers you?

It's a little different, right? So J&J uses modified adenovirus which acts more similarly to real life, in that it's using a DNA transcription process (that's where they think some error occur and causes clotting/stroke issues). Although they are also just making a protein that displays on the outside of the cell. A real virus will create copies of itself via a similar method. These copies are inside of the cell and later leave it.

So it's mostly a concern that in one way we are targeting a spike protein on out own cell, but normally a virus would be complete and not be displayed as part of the cell wall. That's where I wonder if some people's immune system might code off of other normal proteins in addition to the spike. I would have thought there would at least have been a study about autoimmune antibody levels. I found one about severe covid patients having a higher likelihood of having them, but I couldn't find a study looking at the vaccines. It's pretty frustrating that I'm being downvoted for asking what I think is a legitimate question, one that apparently hasn't been looked into (since I can't find any study and the downvoters haven't provided one either).

I think one of the biggest failings in how we handled COVID is lack of challenge trials. We could have had all the vaccines approved months earlier. I'd have been thrilled to volunteer for a challenge trial and still would to accelerate approval of booster shots or mixes of vaccines.

Every day we can get any approval sooner is so many lives saved!

Question: remember when the distribution of these vaccines was a logistical impossibility due to requiring minus 100 temperatures and special freezers and all that? And then it somehow got "solved" and it hasn't been mentioned since? Was it really all that easy? Or is it possible that millions of people are getting thawed or warmed shots that, due to not following extreme procedures, have lost their potency?

That was only a problem in developing countries, and dry ice solved it nicely. That said, the vaccination figures from developing countries are still very low, not in the least because the developed world refuses to pay for it. Though there is some movement on this, it should be painfully obvious by now that as long as there is even one country where this is not under control we can pretty much assume that there will be endless re-runs.

Seems strange that there was any concern whatsoever, if dry ice was a solution. They were talking extremely low temps. Further, we are in the midst of a major trucking shortage... I would have to assume that the small niche of ultra-cold trucking is even more stressed.

Shipping and storage requirements were relaxed as manufacturers were able to complete additional studies.

For example: https://www.fda.gov/news-events/press-announcements/fda-brie...

it said they "submitted data to the FDA", that is very vague as to whether it was actually further studies or some other type of evidence/data

Ya, sorry I used "studies" in the shitty industry jargony way where it (as opposed to clinical study) can mean just about any type of experiment.

For shelf life and storage, FDA typically very much prefers real-time rather than simulated/accelerated data. For the time interval listed here (1 month at fridge), they certainly would have done a real-time study.

I've only worked in diagnostics (and any reagents needed for that), so I don't know if the FDA would require these studies to have an actual human efficacy/safety component, or if these vaccines just passing some sort of QC test (presumably the same screen they use to manufacture) is enough.

The Moderna shot had more relaxed requirements from the beginning, and the Pfizer shot could be stored for a month by adding dry ice to the shipping container.

There was focus on the requirements, but there were lots of people arguing that they weren't that onerous for wealthy countries (and they aren't particularly onerous).

Logistical impossibility due to a lack of specialized freezers. In Canada at least, the federal government just bought a ton of freezers.

What about transportation between factory and destination? And if they just bought the freezers, how were all the doses from Jan to July kept cold?

Dry ice can work for that. https://www.pfizer.com/news/hot-topics/covid_19_vaccine_u_s_...

I am using "just" to mean simply rather than recently. For a wealthy government willing to spend, acquiring freezers is not a problem.

This other study from August 12 found 88% effectiveness against Delta: https://www.nejm.org/doi/full/10.1056/NEJMoa2108891

Can someone please update the link to the latest version

https://www.medrxiv.org/content/10.1101/2021.08.06.21261707v...

What is the latest an how J&J compares with Moderna and Pfizer? Is J&J considered less protective than those, against the Delta variant? Any links to studies will be appreciated.

Wasn't moderna a bigger dose?

Yes, but slightly different dosing interval as well.

Dosing intervals were frequently dictated by vaccine availability and not by the manufacturer mandated schedule of administration.

Pfizer is 30 micrograms per dose, Moderna is 100 micrograms per dose.

I know many will disagree but with the booster shot set for approval any day now, we need to stop calling something a vaccine when 3 doses within a 12 month period of it are needed

In the vernacular, or scientifically?

I think most folks around me call their annual flu vaccine a "flu shot", but I still think it qualifies as a vaccine even though we don't think of it of the same severity as your one-time childhood vaccines.

I don't see why. HPV vaccine takes three doses several weeks apart. Hepatitis B vaccine needs three doses with a month between the first two, then another 4-5 months later. This is really not new territory.

And after the 3 doses the patient has immunity against HPV.

Bloomberg: “A month after the third shot, 55% of those who got it developed antibody levels likely to provide significant protection.”

Only 5% over half were “Likely” plus “significant” which is not definite by a long shot (no pun intended)

https://www.bloomberg.com/news/articles/2021-08-11/third-mod...

Are you expecting the results in people with compromised immune systems to generalize to the broader population?

If so, why?

My point was equating a “multi dose defense shot” to a vaccine.

After the immunocompromised have had the opportunity to protect themselves, the booster will be made available to all, just like the initial shots earlier this year. Those will be followed by another booster or more next year and so on.

Many vaccines don't have 100% efficacy, and diminished protection over time. The point is that if everyone has good enough protection from a vaccine, the outbreaks die down (r_0 < 1).

For example,

One dose of MMR vaccine is 93% effective against measles, 78% effective against mumps, and 97% effective against rubella.

Two doses of MMR vaccine are 97% effective against measles and 88% effective against mumps. [1]

[1] https://www.cdc.gov/vaccines/vpd/mmr/public/index.html#:~:te....

You are supposed to get a tetanus defense shot every 10 years too.

The logic for a booster actually would be defense, it boosts antibodies which helps block more infections. An injection designed to modulate immune response by exposing the immune system to the target antigen is certainly a vaccine though.

Those are immunocompromised transplant patients.

Basically when you get a transplant organ, the body's immune system tries to kill it so they have to use powerful drugs to kill off the immune system.

It still a vaccine. No vaccine ever promised absolute immunity, nor did any of them ever promise protection against materially different strains of the same basic pathogen.

Maybe but then again, the vaccines went from published SARS-CoV-2 genome to vaccine approval in less than a year too. A booster shot under those circumstances seems pretty consistent under that compressed timeframe. 10 years from now people will probably get something more stable with boosters at bigger intervals. A vaccine is a vaccines; just because the virus is evolving quickly doesn't mean it's not. You're still almost certainly way better off with a vaccine than not.

Tetanus vaccines would have to be called something else, as well. I think a lot of vaccines lose effectiveness over time.

Check out the schedule for tick-borne encephalitis vaccine:

http://mri.cts-mrp.eu/download/AT_H_0126_001_FinalPL.pdf

1st dose,

2nd dose 1 month later,

3rd dose 5 months later,

1st booster 3 years later,

additional boosters every 5 years

I think it would be great if we had effective covid vaccines with such a schedule

My first shot was Biontech and I'm still in for the second one. Would it make sense to take Moderna instead of Biontech?

What would this data look like if all of the people with natural immunity from exposure were excluded?

For example, about 33% of the American population was exposed to COVID, according to the CDC [1]

If Pfizer is 42% effective, would that effectiveness value drop even further?

[1] https://www.thedenverchannel.com/news/national/coronavirus/c...

Moderna seems to ve bettee overall (more effextive, effectice against variants, fewer side effects). I ghess time will tell on the safety of mRNA vaccines.

> fewer side effects

From my vantage point, Pfizer had far fewer side effects. One acquaintance who had Moderna got walloped so bad on the first shot that they didn't get their second shot.

Of course, all anecdotes. I'd love to read some better numbers.

I haven't known anyone in their 20-30s who got a 2nd Moderna shot and wasn't down for a day.

My anecdotal experience with the second dose was that I experienced light headedness almost exactly 24 hours after the shot. But, it went away after two cocktails (I was flying that day)

I was 35 at the time and was completely down for a day after the second shot. My girlfriend got Pfizer and she wasn't as badly affected -- just got a little sleepy.

It's interesting to read these different experiences. I'm in my 40s, my second Pfizer just left me feeling mildly tired, with a bit of pain in the arm. My dad didn't have any real symptoms, and my brothers, in their 30s, said they had more flu like symptoms. I actually had planned to be out of commission based on other peoples reports and was surprised when I was basically fine.

I'm mid-40s and had 2x Moderna on the recommended schedule back in Apr/May. First shot was just mild injection-site pain. Second shot was terrible. Symptoms started about 12h after the shot, and I was stuck in bed for ~36-48h of the worst flu symptoms I've ever had in my life (fever, chills, bad whole body muscle ache, etc - basically everything but the usual sinus/cough part).

It was totally worth it, though, and I'd do it again! If you're on the fence - please go get your shot(s)!

FWIW, similar age, Moderna, and just mild injection-site pain both times.

>It was totally worth it, though, and I'd do it again! If you're on the fence - please go get your shot(s)!

As another data point, I wouldn't and don't think it was worth it. Being KO for 4 days when the virus is mundane is not a good trade. (Im 25ish). Plus it doesn't provide 100% protection so I can still get it.

Not sure you can call covid "mundane", given that 620K have died from it in the US...

As I said I'm 25ish. It's a pretty mundane disease for people that age.

https://www.statista.com/statistics/1191568/reported-deaths-...

Potential damage to your lungs, heart, and brain doesn’t seem mundane to me.

The person describing four days of being down is not common and is an extreme case. I myself got a little tired day of, had some mild chills the night of, and was a little sore with a headache the morning after. I took some ibuprofen, drank a lot of water, and ate well, and I felt fine later in the day after. I get the feeling this is very typical.

The response to the vaccine is simply your body preparing itself. Getting the virus isn’t that and has a lot of potential for damage.

That person is me and seems quite prevalent at least in my entourage of young people. How old are you? Age is very important when talking about side effects. Plus the potential damage is less likely for people that age, aka we get the most side effect for the least chance of actually having a bad case of the disease.

P(getting disease) * P(symptomatic | sick) * P(worse than 4 days fever | symptomatic) gets small very fast. Notwithstanding the fact that inflicting damage upon yourself is psychologically worse than chance events like getting a virus.

I had basically the same experience with 2x Pfizer on the 2nd shot.

and yes well worth it and I'll do it again.

I had a little fever (99) and was tired for about 12 hrs. Was not terrible. But I am 63.

I had the Moderna short. Sore arm both times is all I had.

I noticed the same pattern, and the FDA numbers do show worse side effects for Moderna.

https://www.businessinsider.com/covid-vaccine-side-effects-d...

It's probably not a coincidence that Moderna 1) has a higher dose, 2) has more side effects, and 3) is more effective.

I got the Moderna vaccine. The second shot hit me pretty hard, I was definitely knocked down for a day. But honestly I was happy about that, being out for one day and then back to normal isn't that big of a deal, and it's a signal that the vaccine did something significant.

Non-medically educated opinion ahead: I think symptoms of illness are mostly a result of immune system activity, and so vaccine side effects are an indication that the immune system is working hard. That's the whole point of a vaccine.

It was a solid couple days for me after the second shot, with a nasty fever and chills. Once, I can deal with, but I'm seriously not looking forward to the prospect of booster shots every 6-12 months. As someone in an extremely low risk demographic, the cost/benefit seems quite poor.

My uninformed eyeballing of the study linked in this thread is that Moderna might not need a booster, or at least not on the same interval as Pfizer.

The graph of Moderna cases in the linked paper looks roughly proportional to the unvaccinated cases to me, which suggests there was little to no reduction in effectiveness over that time period. In contrast, the Pfizer cases look to be growing more quickly than the unvaccinated cases, indicating a reduction in effectiveness over time.

Time did tell. It was called safety and efficacy trials. They passed.

The side effects have been higher overall with Moderna, but the dose of mRNA you get is also more than 3x that of the Pfizer.

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