2404: First Thing

Explain xkcd: It's 'cause you're dumb.
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First Thing
Then I'm going to go on a weeks-long somatic hypermutation bender, producing ever-more targeted antibodies, while I continue to remain distanced and follow guidance from public health authorities.
Title text: Then I'm going to go on a weeks-long somatic hypermutation bender, producing ever-more targeted antibodies, while I continue to remain distanced and follow guidance from public health authorities.


This comic is another in a series of comics related to the COVID-19 pandemic, specifically regarding the COVID-19 vaccine.

This comic, somewhat like 2402: Into My Veins, references both the COVID-19 vaccine and a common Internet trend. Two comics later in 2406: Viral Vector Immunity, the vaccine is again referenced.

The COVID-19 pandemic has been one of the most consequential and broadly unpleasant events in living memory[citation needed]. As of the publication of this strip, it is estimated to have caused over 1.5 million deaths worldwide and over 300,000 deaths in the United States. Many more cases that have not resulted in fatality often need serious medical support and/or have lasting implications. Even for those who have been spared infection, measures to slow the spread of the virus have been highly impactful and have been ongoing for nearly a year.

In consequence of all of this, many people are excited for the vaccine (which later resulted in the pandemic successfully ending). Many people online have been sharing plans for what they'll do after getting the vaccine, like "see my friends" or "travel the world." In this comic, Ponytail takes the phrase literally, listing not what she will voluntarily choose to do but what low-level involuntary systems in her body will do immediately after getting the vaccine:

  • First she will make some spike proteins. This implies that she took an mRNA vaccine (e.g. from BioNTech or Moderna) or a viral-vector vaccine like the ones from AstraZeneca, Janssen Vaccines, or CanSino. mRNA vaccines contain RNA encoding for the viral proteins, which is then used by Ponytail's cell to make the spike protein. Viral-vector vaccines contain DNA, which the viral "shell" introduces into human cells, which then manufacture spike proteins. (In contrast, subunit-containing vaccines like the ones from Novavax contain actual duplicates of viral proteins to sensitize the immune systems, and inactivated/weakened virus-based vaccines contain the actual virus in question, but modified to not cause disease, e. g. the vaccines from Sinovac and Sinopharm.)
  • The spike protein made by Ponytail will then be recognized by her immune system as foreign (as would the proteins of the real coronavirus) and subsequently engulfed by the dendritic cells in a process called phagocytosis.
  • The dendritic cells then chop the spike proteins into small pieces (called antigens) and present them on their surface using MHCII proteins.
  • This will then allow T-cells to recognize these pieces and become activated if they have a matching T-cell receptor.

The next step is mentioned in the title text:

  • The T-cells will activate B-cells, who will then try to make antibodies to bind the spike protein. Since the B-cells don't know what a good antibody looks like, they just randomly generate antibodies through a process of somatic hypermutation. Then they check if the antibody binds the antigen presented by the dendritic cells. If it doesn't the antibody is discarded, if it does, it is kept and improved on by another round of somatic hypermutation, to create an antibody which binds even better.
  • Finally Ponytail mentions the things she herself (as opposed to her immune system) has to do: continue to use social distancing, hand washing, wearing a mask, etc.

The last point, which are the only things that Ponytail will choose to do is important, for a number of reasons. The vaccines currently available offer a great deal of protection to an individual patient, but that protection takes several days to even begin in a significant way. Full immunity will likely require several weeks and an additional dose. In addition, while highly effective, the current crop of vaccines are not 100% effective. And even those who develop immunity can become contaminated with the virus on their person and then transmit it to others.

For all of these reasons, there is a very real fear of people who receive vaccinations immediately abandoning all other precautions and continuing to spread the virus. Genuinely ending the pandemic will require precautions to remain in place until enough of the population is vaccinated that a combination of high levels of population immunity and other distancing precautions lower the infection rate to a controllable level. Abandoning safety precautions before this occurs could extend the pandemic and cost lives. Accordingly, Ponytail's intent is to be responsible and maintain all appropriate precautions until such time as it's safe to change them.


[Ponytail and Cueball are walking toward the right side of a single panel. Ponytail is gesturing with one arm.]
Ponytail: The first thing I'm going to do after I get the vaccine?
Ponytail: Definitely make a bunch of spike proteins and engulf them with dendritic cells.
Ponytail: Then I'll probably display the antigens to my T-cells...

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Note that Ponytail expects to get one of the mRNA or viral-carrier DNA vaccines, e. g. the Pfizer/BioNTech vaccine or Sputnik 5. Her description would not make sense if she receives the Novavax vaccine (NVX-CoV2373), which contains spike proteins and does not recruit the patient's cells to make them. 04:14, 29 December 2020 (UTC)

for a more detailed explanation of the differences between vaccines read this article: https://qz.com/1950365/what-is-the-novavax-vaccine-and-how-does-it-work/ 05:07, 29 December 2020 (UTC)

How quickly does the immune system start responding to the vaccine? Maybe the actual first thing she'll do is produce a flood of neurotransmitters that represent happiness and relief. Barmar (talk) 05:20, 29 December 2020 (UTC)

In the immediate post-Christmas TV adverts (here in the UK) it was notable that there were many suggesting people book foreign holidays(/vacations), clearly the surviving bits of the hard-hit travel-sector desperately trying to get summer (or earlier?) bookings and deposits to kick-start their return to normal. One ad (eventually, after a day of such saturation) started with "Hooray, the vaccine is here!" before 'seemlessly' flipping to reveal its main message of huge discounts on flights or whatever it was... Whether people are practically thinking of it as 'jab and go' (doubtless many are), firms are certainly relying upon them to do so. (Without even outwardly adressing the fallout from Brexit which will add a little extra frisson of uncertainty to much of the business model.) Such fun(!) to watch unfold... 13:55, 29 December 2020 (UTC)

On one hand, summer holiday is far enough for people not just getting vaccinated but also starting generating antibodies, yet not so far to not make sense to start ordering them. On the other, I suspect the travel-sector is desperate and there will likely be bankrupts, so they might really prefer people being irresponsible ... -- Hkmaly (talk) 00:16, 30 December 2020 (UTC)
The initial priorities set down for UK vaccinations are skewed towards the older age groups and others with health vulnerabilities (mixing in carers and healthcare professionals) where the ninth/least priority level is "all those 50 years of age and over" (...not already included earlier) and is aimed reducing the risks of the top 99% of the mortality-susceptible as quickly as possible. The archetypal "18-30" group (except those healthcarers at priorities 1&2 and ones with underlying conditions that put them in group #6, minorities and neither likely to be big spenders on foreign travel) and most members of any family setting off for sun/sea/beach will have to wait until after this comprehensive first set of phases are (effectively) complete to get in on the bonus. This could be as early as springtime if it all goes well, but easily could be so disorganised as to be up to half a year later than that. 02:59, 30 December 2020 (UTC)

I think the explanation about maintaining other mitigation measures misses an important point: some (perhaps all) vaccines have not yet been shown to reduce transmission, as the primary outcome of studies was to reduce the COVID19 disease (symptoms), and was not to reduce either infection or transmission. In other words, the vaccine will help me from getting sick, but won't prevent me from being infected or passing it on. (https://theconversation.com/a-covid-19-vaccine-that-prevents-both-the-disease-and-viral-transmission-is-the-aim-until-then-heres-what-we-need-to-do-151839) Jezzaaaa (talk) 03:52, 8 January 2021 (UTC)