InfoMullet: Moderna Joins Pfizer in the ‘Pfight Club’ of COVID19 Vaccines

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InfoMullet is collaborating with Science Decoded to bring a series of articles on COVID19 and vaccine release. To view more of Science Decoded’s content including live-updates, Ask Me Anything videos, and even a few COVID19 related memes check them out on Facebook.


TLDRUpFront: There is a lot of promise in Pfizer’s announcement, but we should be cautious about investing too much hope in it too soon. It bodes well for the pandemic long term, and I hope that we get similar announcements from AstraZeneca and Moderna soon, but there are major challenges ahead in both approval and delivery of safe, effective vaccines. We need to be candid about those, even as we celebrate this positive turn in the history of the pandemic.

And now with Moderna. Player 2 has joined the game.


FullContextInTheBack: This one has a LOT of complexity to it, so lets start with a section-by-section breakdown that will let you jump forward to the parts you care about. Section One will contain a breakdown of the basic technology being employed, and why the way these particular vaccines are being made necessitates – or how it doesn’t – the storage and shipping limitations we will get into later. Section Two will be about the vaccine approval process generally, and the details of where Pfizer – and Moderna, and AstraZeneca, and others – are in that process (or those processes; we’ll get to that). Section Three will be on the logistics of vaccine distribution and use, and how the choices made early in vaccine development might complicate vaccine delivery later on. Section Four will delve into the timeline of vaccine delivery, and when we can expect that health care workers, first responders, vulnerable populations, and finally the general public will receive this vaccine. Finally, I ask you to bear in mind that I am giving you a “best guess” analysis, and many of the unknown factors may greatly affect these predictions… and so, I MIGHT be completely wrong. I hope I’m not, but in the interest of giving you something rather than nothing, I’m going to give my best guess of where we are and where we can expect to be in 2021. Each section will have its own header, so if you are interested in only some of those topics you can easily skip to the right section. I will also have a conclusion at the end, where I synthesize all of that information into what I feel is a core takeaway from all of those information.

On with the show.


This topic can (rather unsurprisingly) get complicated FAST, but I’m going to only go into those complexities that I think are relevant to the average reader. That is the same standard I will use for all the sections going forward, by the way.

At its most fundamental, a vaccine is like an immunological “fire drill.” It stimulates your immune system in the particular way that it needs to be stimulated, in order to be able to effectively respond to a given virus – or other pathogen – going forward. That means that you DO have an immune reaction, and so people experience all the symptoms that go with that – congestion, inflammation, fever, etc – but do not actually become infected with a dangerous pathogen. There are several ways to do this. Some of the more popular (with the most relevant one listed last) are:

Variolation (VAR): expose a person to a less-deadly cousin of a given pathogen, on the assumption that the practice their immune system has against that less-deadly cousin will let them fight off that more deadly pathogen when they encounter it. When you hear about Cowpox being used to fight Smallpox, that is precisely what you are hearing about. This is the oldest kind of immunization, and in a sense it is not even a vaccine because in this scenario you DO become infected with a virus… but you get LESS ill than you would if infected with the more deadly pathogen actually being targeted. This is the general principle behind the BCG (Bacillus Calmette-Guerin) pneumonia being developed right now by the University of Melbourne against COVID-19.

Live Attenuated/Inactivated Virus Vaccines (LAIV): similar to variolation, with this a person is exposed to a weakened or altered version of a pathogen which teaches them how to properly get “suited up” to fight the real thing when it comes around. It is also one of the older forms of vaccine technology, and also exists right on the edge of what we consider a modern vaccine since it TOO gets people actually sick to some degree to keep them from getting more sick later. This is the kind of vaccine being developed right now by the (Russian) Gamaleya Research Institute against COVID-19.

Dead/ Virus Vaccines (DIV): Taking LAIV a step further, DIV vaccines completely kill a given virus but inject people with the dead remains of that virus in order to train their immune system to know what to look for. It is the first on this list that DOESN’T get a person genuinely ill, because the virus can no longer replicate once rendered dead/incompetent, but because the immune system reacts to its presence there may well be immune symptoms. This is the kind of vaccine being developed right now by Johnson & Johnson, Bharat Biotech, and Sinopharm against COVID-19.

(In case it’s note clear, “incompetent” – when used in reference to a living or semi-living thing –  means it is not capable of performing some particular function. In this case, it refers to a virus that cannot replicate itself inside a host. For a virus, that is functionally equivalent in most ways to being “dead.”)

Synthetic Viral Particle Vaccines (SVPs): In this method, scientists take viral particles from a virus that is known to induce a strong immune response – like Rabies or Measles – and then remove the infectious parts and alter the parts of it that are needed to make it specific to the target pathogen, so that it results in immunity to the target pathogen instead of the original pathogen. This takes some tinkering to get right, because it depends on knowing just how much you can alter a viral particle and in what ways you can alter it, while making sure it retains effectiveness in achieving the purpose you are setting out to achieve. This is the kind of vaccine being developed right now by the University of Pittsburgh and Thomas Jefferson University against COVID-19.

Viral Antigen Vaccines (VAVs): Instead of injecting people with the WHOLE virus, scientists isolate JUST those pieces that are recognized and responded to by the immune system (the surface proteins in Influenza, the spike proteins in Coronavirus, etc) and replicate large numbers of those, then inject them into a patient. This CANNOT make a person truly ill, because no viral genetic material – or even whole virions – are present, but again it may cause an immune reaction that feels very much like getting sick for a few days. This is the kind of vaccine being developed right now by the University of Sasketchewan, GlaxoSmithKline and United Biomedical against COVID-19.

Modified Non-Pathogentic Virus Vaccines (MnPVs): In this sort of vaccine, we take a virus that is mild or innocuous in the human population (usually an Adenovirus) but that is good at attaching to human cells and delivering its genetic package inside the cell… and then do a bait-and-switch where we alter the package so that it is no longer the virus’s genome, and is instead nucleic acid that sets that cell up to make antigens that then work like a VAV factory within the body itself. The complication from this is that someone might have antibodies against the virus – the Adenovirus, usually – used to deliver the nucleic acid, and that may reduce the effectiveness of the vaccine. In essence, with a platform like this you can become immune – to some extent – to the vaccine itself. This is the kind of vaccine being developed right now by AstraZeneca, Merck and CanSino Biologics against COVID-19.

Encapsulated Nucleic Acid Vaccines (ENAVs): The sort of vaccine builds EVERYTHING from scratch. Instead of starting with an existing virus or existing viral particles or proteins, it relies upon a synthetic lipid (fat) bubble that houses a synthetic mRNA, used to program your cells to temporarily make viral proteins that cause an immune response. It relies on existing systems that we know cause the mRNA to get injected into cells, and upon the knowledge we already have in how to make your cells temporarily make proteins we want them to make, in order to turn your own cells into temporary vaccine factories. The antigens they make cause your body to go through a natural immune response, making antibodies that neutralize the proteins of interest and hopefully protect you against the virus itself. This is the kind of vaccine being developed right now by Pfizer and Moderna against COVID-19.

… and that really only captures about 2/3 of the vaccines being developed against COVID-19 right now. There are a LOT of ways to achieve this particular objective, and so as a result there is a lot to talk about here. This could be a course unto itself at the graduate level, if I really went into the complexities of this topic. But, that’s not why we’re here.


Just one page of several listing the vaccines currently winding their way through the approval process in various countries.

The important differences between them really come down to what material they use to kick off the immune cascade, how reliable the immune reaction is to then provide protection against illness, how durable that response is (i.e. how long it lasts) and thus how often one needs boosters, how straightforward it is to develop with modern molecular technology, and how fast it can be developed/deployed with the same. If I were to rate each of the preceding categories of vaccine on those three dimensions (and bearing in mind it is MUCH more complicated than that, to the extent that one could justifiably have very different ratings for each and not be wrong), it might look like this:


1 = most stable material, most reliable protection, most durable protection, highest ease of development. 5 = the opposite of all that. I am also ONLY assessing COVID-19 vaccines here – vaccines against other pathogens might be rated very differently.

Note the bolded elements that are the strengths of that vaccine platform, and the weaknesses of each platform. Knowing those will help you to understand why the first ones to reach approval were ENAVs.

You can see by the side-by-side comparison that the one primary virtue of ENAVs is speed of development. Within mere weeks of COVID-19 being declared a pandemic, for instance (or even before that point) labs in Seattle, China, Atlanta, and elsewhere were most of the way to having a viable ENAV platforms targeted against COVID-19. The rest of the time since then has been dedicated to testing it, perfecting it, and addressing the many other challenges of deploying the vaccine to the whole population.


Before we move on, though, I want to talk about the basic technologies used to ADMINISTER a vaccine to a person. This is the often-underappreciated part of vaccine development and delivery that will come up MUCH more later. But, for now, I want you all to have it in your minds that to deliver a vaccine you need:

  • A glass vial that stores the vaccine
  • A refrigerator or other stationary storage container that keeps the vaccine at an appropriate temperature prior to use
  • A needle that delivers either the whole contents of the vial or an amount from inside it (called an aliquot) that is the dose one person needs
  • Boxes, trucks, trailers and airplanes that can hold tens, hundreds or thousands of doses of the vaccine in transit as they move from where they are produced to where they are consumed


All of these are fail points. If any of them lose power at the wrong moment, crash, or are damaged then they could compromise the vaccine being delivered or the dose received by the patient.



We all are probably somewhat familiar with the general vaccine approval process by now, but I want to refresh our knowledge and expand on a few points.

Basically, the vaccine approval process can be broken down into these three (very much oversimplified but done so you get the point) phases:

Phase 1: Give the vaccine to a few dozen monkeys and see if any of them die/get sick/whathaveyou. Measure if there is an immune effect, but know that you aren’t PROVING effectiveness at this point so a positive signal is just gravy.

Phase 2: Give the vaccine to a few hundred humans and see if any of them die/get sick/whathaveyou. Measure if there is an immune effect, but know that you aren’t PROVING effectiveness at this point so a positive signal is just gravy.

Phase 3: Give the vaccine to a few thousand humans and see if they get sick at the same rate as equivalent people who get the placebo. Also, monitor them for adverse reactions over the course of the trial. Go until you get enough total infections in the study population that it is statistically certain, significant, and proven, and so that you have followed the subjects long enough to be reasonably certain the vaccine isn’t doing anything adverse to them in the short- or medium-term.

Pfizer, Moderna, AstraZeneca, Bharat BioTech, and Johnson & Johnson are ALL in Phase 3 right now (see Illustration 3 and the RAPS link in the biography for more about where they all are). Those vaccine trials all have several “checkpoints” built into them based on the total number of confirmed cases in the studied population, or median length of time post-vaccination (the former is an interim checkpoint for efficacy, the latter for safety). At each checkpoint the company running the trial either reviews or (more commonly) forwards their raw data to a third party to review for them, and asks that independent review board to tell them what those data mean.

Pfizer has reached the first efficacy checkpoint (they planned it for when they reached 64 cases in the study population, but the negotiations took so long they have 95 confirmed cases by the time that number was agreed upon); at time of writing, none of the others have reached any of those checkpoints yet [after-publication note: Moderna has reached this milestone now, showing ~95% efficacy]. After forwarding their data to an external review panel [Moderna’s process is slightly different, as it IS involved in Operation Warp Speed], that panel told them that the vaccine appeared to be >90% effective at preventing infection by COVID-19. It is important to know that Pfizer had no control over the findings of that panel, and that the FDA had no control over the process at all. That is because Pfizer opted out of the US FDA’s Operation Warp Speed (OWS), citing needless bureaucratic burdens which would slow development. OWS centralized and controlled the Phase 3 trials of the various vaccine candidates, ideally in order to keep them moving forward as fast as possible. Moderna and AstraZeneca ARE involved in OWS, so we will see how that goes when they reach their first checkpoints.

It is also important to know that those results, while handled and processed by a body independent of Pfizer, have not been made public yet. They will not – or SHOULD not, at least – be acted upon until they are. Until the scientific community can judge the findings for itself, transparently in the open, it is impossible to truly trust them to the extent that we put thousands of peoples’ lives in their hands.



Finally, while not DIRECTLY related to this, I want to issue a caveat about assuming the 90% number is representative of the overall effectiveness of the vaccine over the whole study period. We have all just gone through a GIANT exercise in the US Presidential election in how results can change as time goes on, and the first checkpoint results might be somewhat akin to the election night ballots in that election. As we all know, things changed remarkably as ballots kept being counted later… and it is almost a certainty that the efficacy of the vaccine will drop as time goes on. The Phase 2 trials even showed that the fundamental immune titers of the studied population dropped past the three month mark, so it is probable that as time goes on that 90% number could come down to 80%, 75%, 67% or something lower than that. No one can know at this point how much change we will see, but SOME change is almost inevitable. It is important to be prepared for that. If it drops below 50% then that will seriously compromise final approval of the vaccine, but depending upon the timeline over which that is studied it might be deemed to still be worthwhile to deliver to critical persons and/or vulnerable populations.



We have all probably read the headlines saying that Pfizer, Moderna, and AstraZeneca have made hundreds of millions of doses of vaccine even prior to their being approved for use. Let us for the moment assume they ARE approved for use, and talk about the oncoming challenge of delivering them to the American people.


The Pfizer and Moderna vaccines are both ENAVs – synthetic lipid particles that encase an mRNA – and as such need to be stored at incredibly cold temperatures, specifically about -80 Celsius. That temperature needs to be maintained in transit from the point of production to the point of use, and the vials can only be set on the counter-top at room temperature for an hour or so before degrading past the point of reliable use. For simplicity of packaging, also, each vial contains between 5 and 20 “shots” of vaccine, and each of the two vaccines requires two “shots” given 2-3 weeks apart in order to provide full protection. That can give us an idea of the potential for “waste” and “spoilage” in the vaccine pipeline, which means those numbers cited earlier – 100 million or more – might come down quite a bit.

In the average doctor’s office, one patient is scheduled per 15 minute block. That means that if one vial is opened per hour then between 20% and 80% of the doses in a given vial are possibly going to be wasted, and that the total number of doses needs to be divided by at least 2 because 2 doses will be needed per patient.

Starting with 100 million doses that gives us: 100 million / 2 = 50 million * 0.8 = 40 million doses at a maximum.

Similarly: 100 million / 2 = 50 million * 0.2 = 10 million doses at a maximum.

And that is assuming 0% wastage or spoilage in transit, which is unrealistic. Trucks breaks down, auto accidents happen, power outages happen, and cold storage integrity is sometimes lost as a result. A 90% assumption is probably within the realm of possibility although rosy, then, and 80% likely more reasonable. Added into our above calculations that results in a range of: 36 million – 8 million patients ultimately able to be vaccinated.

Another complication is expiration. The vaccine can only be held, even at -80 Celsius, for so long. It degrades past that point, and cannot be used. That means that logistics pipelines need to plan for how many patients every SINGLE doctor’s office, clinic, hospital, mass vaccination site, military vaccination site, community popup clinic, and other facility can vaccinate per day, and they need to maintain that stated scheduling in order to avoid having more vaccine on hand than they can use per unit time. It is impossible to say how well logistics pipelines will plan for or implement this, but it is a factor that needs to be considered.

Finally, corruption. It is INCREDIBLY likely that with a product as valuable as a life-saving vaccine against an illness of global importance, there will be a black market. That black market will be composed of (1) stolen product, (2) expired or compromised product and (3) illegitimate/faked product. The final two groups are not important to consider in terms of vaccine delivery since they are already “lost” vaccines, but the first category needs to be watched for. That is especially true if vaccination rollout schedules mean that the average person – especially the average rich/powerful/greedy person – cannot get vaccinated for months after release. That delay will create a black market, and that means that some product will be lost by falling off the back of a truck and illegitimately into private hands.

All of these things complicate delivery, and while is it not possible to know the magnitude of many of them, how they will interact with one another will ultimately mean that the number of doses of vaccine made will far exceed the number of people who get vaccinated. That will be fixed, ultimately, with continued production and delivery and with the approval of more than one vaccine… but in the initial months of vaccine rollout, that may well be leaving many people with a whole lot of headaches.



There are many reasons for phased delivery, but foremost among them is that we are in an emergency and need all health care hands on deck inasmuch as that’s possible. After that, we need to protect vulnerable people. After that, we immunize the rest of the herd.

The average person is not going to be first in line to receive a vaccine basically anywhere. Because of limited doses and the need to step-up logistics pipelines rather than activating a whole network on day one, all of the states I have examined have planned for a phased delivery schedule. In general, it goes like this:


1st Phase: Health Care Workers and VIPs (elected officials, national security personnel, etc)

2nd Phase: First Responders (police, EMTs, firefighters)

3rd Phase: Vulnerable populations (prisoners, nursing home patients, patients with comorbid conditions, the elderly, etc)

4th Phase: Everyone else


That means that, assuming a vaccine is approved under an EUA in mid-late November, the 1st Phase can start by Christmas. The 2nd Phase can start in January or February. The 3rd and 4th phases will likely need to wait for full approval rather than an EUA, but if that is forthcoming then that can start in February or March or April. Finally, the 4th Phase can start in March or April or May.

New York State’s Phased Vaccine Distribution Plan


So, if you are a healthy person, do not expect a vaccine before at least late Q1 2021, but more likely Q2 or Q3 2021 as the vaccine slowly disseminates into a population of 300 million people. It will take at least ~6 months to make enough of a single vaccine to deliver to that population of people, and though it is likely several will be approved by then it is also nearly certain that new implementation challenges will be identified in the mean time which slow that process somewhat.

I know that the last few sections have been me throwing “cold water” on the prospects of something very exciting, and I do not like doing that. I take no pleasure in dashing hopes, especially after the year we have all had… but I don’t think I’d be doing you any favors if I told you anything less than the whole truth, or let you keep unrealistic pictures in your minds. That said, this news from Pfizer IS a BIG DEAL. It is a first, exciting finding of efficacy, it is a positive signal, it is GOOD NEWS in a year where that has been few and far between. That is no small thing. I will keep informing you about this and other questions as best I can, and in the mean time I want to help you stay in an optimistic but realistic frame of mind as to how the next few months might go.