What’s the Difference Between the MMR and MMR-II Vaccines?

As most folks know, the original MMR vaccine, which combined the separate measles, mumps, and rubella shots, was licensed way back in 1971.

It included the original rubella vaccine, which was made with a duck embryo derivative of HPV-77 that was attenuated by passing it 77 times in monkey kidney cells.

Wait, what?

HPV?

Before the new conspiracy theories start, no, not that HPV.

It stands for High Passage Virus.

What’s the Difference Between the MMR and MMR-II Vaccines?

And while the vaccine worked, it didn’t work as well and caused more side effects than a RA27/3 rubella vaccine that was already approved in Europe

“Over the next decade, accumulating evidence led to changes in the United States. First, the duck embryo and dog kidney vaccine strains caused significant joint reactions [24–27]. Second, reinfection on exposure to wild rubella virus was demonstrated frequently with all strains except the RA 27/3 vaccine [28–30]. Third, the good safety record of the RA 27/3 vaccine in Europe, plus the majority opinion of scientists, led the US Food and Drug Administration to license RA 27/3. Important pressure for this decision came from Dorothy Horstmann at Yale, who was convinced by her comparative studies of rubella vaccines [31], and by Maurice Hilleman at Merck, who sought a better rubella strain for measles-mumps-rubella (MMR) vaccine.”

Stanley Plotkin on The History of Rubella and Rubella Vaccination Leading to Elimination

So that’s it, they just changed out the rubella component for one that was safer and worked better.

The new and improved MMR-II vaccine was approved by the FDA in 1978.
The new and improved MMR-II vaccine was approved by the FDA in 1978.

And of course, they did the appropriate clinical trials and got FDA approval for this updated vaccine.

The control group didn't get a vaccine during the study.
The control group didn’t get a vaccine during the study.

But did they compare the vaccines against a saline placebo?

“The inclusion of a seropositive control group allowed the rates of reaction to be viewed against the background symptoms unrelated to vaccine administration.”

Polk et al on A controlled comparison of joint reactions among women receiving one of two rubella vaccines.

They actually went a little further, in a double-blind, controlled cohort study comparing it to folks who didn’t receive any vaccine at the time of the study!

Why so many joint issues with the vaccine?

The studies were in adults, who seemed to have more side effects with the vaccine. Still, the side effects, including arthritis, were transient.

What about the idea that it was studied long enough before being approved?

Both the rubella component and the MMR-II vaccine were studied both before and after being approved. In fact, the MMR-II vaccine is probably the most studied vaccine in history!

Believe it or not, they include placebo-controlled trials.

A double-blind, placebo-controlled, cross-over MMR study in twins!

What was the placebo in the Finland twin trial?

“The injections consisted of 0.5 ml of vaccine 2-5 or placebo (the same product including neomycin and phenol-red indicator but without the viral antigens) and were administered subcutaneously by the nurse to the left deltoid or gluteal region.”

Peltola et al on Frequency of true adverse reactions to measles-mumps-rubella vaccine. A double-blind placebo-controlled trial in twins.

If that doesn’t sound like a placebo to you, keep in mind that the MMR vaccine doesn’t contain that many ingredients. Remember, MMR doesn’t contain aluminum or thimerosal. And if the placebo didn’t contain the antigens, then it likely didn’t contain all of the things that went into getting those antigens in the vaccine, such as cell cultures and albumin, etc.

Still, some folks aren’t going to be satisfied unless there is a study with a saline placebo.

“The four other vaccines were commercial products of Merck Sharp & Dohme. The placebo consisted of vaccine diluent.”

Lerman et al on Clinical and Serologic Evaluation of Measles, Mumps, and Rubella (HPV-77: DE-5 and RA 27/3) Virus Vaccines, Singly and in Combination

The vaccine diluent?

What’s that?

It depends on the vaccine, but for MMR-II it’s sterile water.

“Placebo DTP consisted of sterile saline which was dispensed into sterile Tubex syringes.”

Deforest et al on Simultaneous Administration of Measles-Mumps-Rubella Vaccine With Booster Doses of Diphtheria-Tetanus-Pertussis and Poliovirus Vaccines

The MMR vaccine was even tested in placebo controlled trials with other vaccines!

And like other vaccines, the MMR vaccine has been found to be safe, with few risks, and is definitely necessary.

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4 thoughts on “What’s the Difference Between the MMR and MMR-II Vaccines?

  1. I was very interested in your comment that MMR has indeed been trialled with a true inert placebo and eagerly went to look at the linked study (which was designed to look at effects of simultaneous administration of DTP and OPV with MMR, versus not). However, the linked abstract advises “The study was double blind and placebo controlled with respect to DTP and OPV”. None of the direct quotes provided are inconsistent with that (and the quote relating to sterile saline did in fact relate to DTP in particular) so I’ve no reason to believe the abstract is incorrect or misleading. My guess would be that there has been a false inference made here – that by taking references to “placebos consisted of vaccine diluent” and an example of how that worked for DTP, it has been inferred that something equivalent was done for MMR, when the text from the study’s abstract suggests that there was no placebo control used for MMR at all, and hence references to the “placebos” used relate to DTP and OPV placebos only (which kind of makes sense given the effects they were specifically looking for). I expect that needs correcting.

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