What risks from vaccines?

Just came across this clip from an interview with Paul Offitt that is relevant here: He claims that, out of all the serious side effects resulting from vaccines in the past that he could think of, all emerged within 6 weeks, so the fact that vaccine trials are required to look 2 months after the second dose before applying for an EUA should mitigate most safety concerns.

As another commenter suggested, one exception could be antibody-dependent enhancement (ADE), in which antibodies induced by the vaccine could enhance the severity of subsequent infection—indeed, this concern was not widely appreciated with the dengue vaccine Dengvaxia until years of post-licensure safety follow-up. But at least the specific mechanism of ADE that is operative in dengue is unlikely to be relevant with COVID-19 (ADE with dengue involves vaccine-induced antibodies against one serotype not being able to neutralize another serotype; the antibodies will still bind to the virus, though, and bring the virus to immune cells, which the virus then infects. But SARS-CoV-2 doesn't have multiple serotypes, and does not seem to be able to infect immune cells.)

What risks from vaccines?

"mRNA vaccines get produced by hela cells which are a cell line based on human cells and as a result there's less reason to expect food allergy development due to mRNA vaccines."

This isn't quite right. One of the major advantages of mRNA vaccines over, say, recombinant protein vaccines, is that you don't need a cell line at all — once injected into your body, the mRNA finds its way into your own cells and your own cells begin producing the encoded protein—the business end of the vaccine—for you!

The process for growing up mRNA in the first place involves growing up a plasmid (circular DNA template) in bacteria, then isolating the DNA from the bacterial cells, linearizing the DNA template using an enzyme, then transcribing (turning DNA to RNA) the linearized template with RNA polymerase in vitro (i.e., not in cells at all — it's just purified polymerase + DNA). But yes, no particular reason to expect food allergy development.

Has the effectiveness of fever screening declined?

It's worth noting here that coronaviruses are less vulnerable to selective pressure than most RNA viruses given that that they unusually encode proofreading activity, limiting genetic diversity. This article ( ) claims that SARS-CoV-2 accumulates 1-2 mutations per month (its genome has 30,000 bases), which is...enormously inadequate to make even the smallest dent anytime this year in the monumental task that is modulating host immunity to modify onset of fever.

LessWrong Coronavirus Agenda

Hmm, well that book chapter claims measles and mumps vaccines are produced in chick embryo cell culture, which is different from propagation on chicken eggs. My quick Googling revealed that we don't have a licensed herpes vaccine, and that while there might be one or two smallpox vaccines that are produced in chicken eggs, many are done in cell culture.

You might be right about the broader (and more important) point about ease of facilities repurposing, however - I don't know enough to say, although the table in the book chapter makes me doubtful, given that pretty much all steps in the manufacturing process (production, isolation, purification, formulation) seem unique to each vaccine.

Does the 14-month vaccine safety test make sense for COVID-19?

This is correct. We have lots of infrastructure and expertise for making new flu vaccines every year. It's not a good model for how long we should expect safety testing to take for a vaccine for a new virus. We don't have any licensed vaccines for any coronavirus, for example.

LessWrong Coronavirus Agenda

FWIW, eggs are actually specific to influenza vaccine manufacturing. Page 3 of this book chapter ( ) has a really nice table showing the production process of a number of different vaccines - they are all very different from one another. This is why we need new vaccine platform technologies - i.e., tech that can be used to produce multiple different vaccines. mRNA vaccines would fall into this category and is a reason why Moderna's mRNA vaccine candidate for COVID-19 would be so exciting if it works.

How hard would it be to attack coronavirus with CRISPR?

It was only a matter of time before somebody tried this:

From the abstract: "Here we demonstrate a CRISPR-Cas13-based strategy, PAC-MAN (Prophylactic Antiviral CRISPR in huMAN cells), for viral inhibition that can effectively degrade SARS-CoV-2 sequences and live influenza A virus (IAV) genome in human lung epithelial cells. We designed and screened a group of CRISPR RNAs (crRNAs) targeting conserved viral regions and identified functional crRNAs for cleaving SARSCoV-2...The PAC-MAN approach is potentially a rapidly implementable pan-coronavirus strategy to deal with emerging pandemic strains. "

Why isn't increasing ventilation of public spaces part of the best practice response to the Coronovirus?

Here's a good op-ed on this topic:

The author suggests that the lack of attention on building ventilation is due to uncertainty about how important close contact (i.e., close enough that a person's respiratory droplets could directly land on you) is for transmission, vs. more indirect airborne transmission.

(E.g., from CDC website: "Early reports suggest person-to-person transmission most commonly happens during close exposure to a person infected with COVID-19, primarily via respiratory droplets produced when the infected person coughs or sneezes. Droplets can land in the mouths, noses, or eyes of people who are nearby or possibly be inhaled into the lungs of those within close proximity. The contribution of small respirable particles, sometimes called aerosols or droplet nuclei, to close proximity transmission is currently uncertain. However, airborne transmission from person-to-person over long distances is unlikely.")

Open & Welcome Thread - February 2020

You might also be interested in the 1976 mass vaccination program in the US for swine flu, which was a case of perceived overreaction (given the anticipated pandemic never materialized) and also hurt the reputation of public health generally:

Or in "The Cutter Incident" in 1955, where a rush to get a polio vaccine out in advance of the next polio season resulted in some batches containing live polio virus, with several children receiving the vaccine actually getting polio instead:

There's definitely a history of incidents in public health of perceived overreaction followed by public backlash, which could potentially be playing into public health officials' heads nowadays. I don't know if becoming more conservative and less-quick-to-take-action is necessarily a wrong lesson, though – even if you think, just simply on the numbers, that taking preventative measures in each of these incidents was correct ex ante given the stakes involved, reputational risks are real and have to be taken into account. As much as "take action to prepare for low probability, high consequence scenarios when the expected cost < expected benefit" applies to personal preparation, it doesn't translate easily to governmental action, at least not when "expected cost" doesn't factor in "everyone will yell at you and trust you less in the future if the low probability scenario doesn't pan out, because people don't do probabilities well."

This does put us in a bit of a bind, since ideally you'd want to have public health authorities be able to take well-calibrated actions against <10%-likely scenarios. But they are, unfortunately, constrained by public perception to some extent.

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