Moderna Partial Results Part 1

Every year I get a quadravalent flu shot made by recombinant DNA technology. This is not a subtle anti-vaxer piece. But for that nutcase movement,  I would have no qualms about what I am about to say, and has to be said. This is about vaccine safety culture.

In the 1950’s and 60’s. the first effective vaccine against polio, developed by Jonas Salk, was replaced by the Sabin live-virus, which was itself replaced by a series of improvements on Salk. The story of polio vaccines makes a tense read, marked by patient tragedies and accusations of murder, yet driven by desperation to chance  Hippocratic Oath #1: Do no harm.

I think the chance is worth taking.  But the front runners present a challenge, to both  safety culture and to the public eye, that hasn’t been seen since the days of polio.

The most dangerous vaccine in widespread use is 17D for yellow fever. An old number was 1 per 50,000 chance of death from the vaccine. The number has been revised downward,  but remains risky for age > 60, so pick your own. (Oxford) Immune Response during Adverse Events after 17D-Derived Yellow Fever Vaccination in Europe.

Yellow fever 17D is a live virus vaccine.  It contains a mutated, non-virulent strain of the yellow fever virus. In rare cases, the weakened virus can cause disease similar to the real thing. (CDC) Reactions to Yellow Fever Vaccine. Even with the old number, 1 in 50,000, regions affected by yellow fever preferred vaccination with 17D to the disease itself.  The choice is baked into these cultures through centuries of yellow fever tragedy.

Americans are still in the novelty phase with COVID, where suspicion rules over logic. Though not related in technology, yellow fever 17D may be the example of what is yet come, a vaccine that saves lives, yet rejected by the public as a dice roll they want to skip. (Reuters) Exclusive: A quarter of Americans are hesitant about a coronavirus vaccine – Reuters/Ipsos poll.

Though live-virus for COVID is not likely to be funded in the developed countries, new vaccine technology may hold surprise in the form of  risk unbounded  by experience. The risks will be reduced in a replacement cycle, with perhaps 6 iterations:

  • First Response. Mediocre but fast.  High incidence of adverse events, compared to other approaches. May produce intolerance to re-vaccination. Immunity may be  short-lived.  Even with net public health benefit, may be rejected by the public.
  • #2: Safer vaccines, with fewer adverse events.
  • #3:  Seasonal administration, without restriction on the number of inoculations.
  • #4: Effective against multiple strains with just one or two shots.
  • #5: Produce immunity for decades with just one shot.  With the technology now available, in technical conflict with #4.
  • #6: Require no refrigeration in storage or transport.

The   complexity of the immune system is unfathomable.. Yet the vaccine world can be (almost) neatly split in two, with a division into 2 kinds, classic and novel. The classic vaccine seeks no change in the body save a normal immune response to antigens in the shot. Many novel vaccines contain active principles that alter the machinery of cells.

The classic dead virus vaccine contains, among other things, antigens, which the immune system reacts to by making antibodies. The other things are dead viruses, pieces of viruses, stabilizers, adjuvants, or unavoidable contaminants. The second goal of the vaccine maker is to ensure that these other things, except for the adjuvant, do nothing.  The classic dead-virus vaccine is inert, playing no role other than to be destroyed by the aroused immune system.

The classic live-weakened virus vaccine adds one active principle, the virus-made-harmless.  As polio and yellow fever 17D show, ensuring harmlessness is a challenge. Test cohorts must be followed for many years.  But 150 years of experience has fostered live-virus vaccines of exemplary safety.

The novel vaccine arrived in several steps:

The recombinant vaccine behaves in the body like a superior classic vaccine. The injected antigen, or antigen particles, are almost completely inert, serving no purpose other than to present antigen to the immune system.

  • Nucleic acid (DNA, RNA) vaccines  abandon inertness. Instead of supplying antigens, these vaccines modify the cell machinery at the injection site for varying periods of time.
  • Virus vector vaccines use an adenovirus to carry nucleic acid into the cell.

The most novel-of-the-novel  include at least one bullet.  Some include both, each presenting novel risk. The risks may be more than additive.

This is not an indictment, or a guide to buying stocks. These are points to watch for. The novel vaccines are diverse; sharing an acronym does not imply  a shared hazard. Yet as Golda Meir used to say, even paranoids have real enemies.

There is more to say, so it will be continued shortly.

 

 

 

 

 

 

 

 

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