Mixing and Matching Vaccines

This page is kind of out of date.

I wrote a big long post laying out the advantages and disadvantages of taking AZ or mRNA after getting a first dose of AZ. That advice was BC-focused, and included considerations about vaccine availability.

This page includes some material from that posting, but focuses on scientific findings about the effectiveness of mixing vs. matching, as opposed to trying to help you make a decision between AZ or mRNA.

Antibodies

• There have been a lot of studies on AZ+Pfizer in test tubes. All of them found that AZ+Pfizer generated higher levels of protection (as measured by levels of antibodies, neutralizing antibodies, CD4+, CD8+, IgG, and/or plasmablasts). They all found that AZ+Pfizer levels were comparable to Pfizer+Pfizer levels, or occasionally slightly better.
  • a big one in the UK called Com-CoV (830 vaccinees) (which had multiple papers come out of it),
  • a Spanish one (676 vaccinees),
  • a small German study in Berlin (340 vaccinees),
  • a small German in Saarland (216 vaccinees),
  • a tiny German study in Ulm (26 vaccinees),
  • a medium German study in Cologne (480 vaccinees),
  • a small German study in Hannover (129 vaccinees)
  • a tiny German study in Kiel (59 vaccinees)
  • a small German study in Berlin (380 vaccinees)
  • a tiny German study in Hannover (23 vaccinees) which included Delta
• A later COM-CoV paper found that AZ then Pfizer wasn’t as good as Pfizer then AZ for antibodies. It found that Pfizer+AZ and Pfizer+Pfizer were about the same.
• This study from Sweden (88 non-randomized vaccinees) found that AZ+Moderna yielded ten times as many antibodies in test tubes as AZ+AZ.
• There have been some other studies which include vaccines which are not approved in Canada (like Sputnik V). I have not tried to keep up with those. Dr. Hilda Bastian is a great source for vaccine info, and a section of her 1 July 2021 blog post talks about mix and match studies.
• The COM-COV2 study of antibodies after vaccination with AZ or Pfizer followed by Pfizer, Moderna, Novavax, or AZ found that
  • Pfizer+Moderna was best, then by Pfizer+Pfizer, followed by AZ+Moderna, although those were all very close (~16K-23K ELU/mL).
  • mRNA+Novavax was next (~6-9K ELU/mL)
  • AZ+AZ sucked (~2K ELU/mL).

Side effects

• The Com-CoV study found AZ+Pfizer side effects were still mild, meaning “no lasting damage and over pretty quickly”, but possibly quite unpleasant.
• The tiny Ulm study said that the side effects were “in line with previous reports” and that the Pfizer second shot side effects weren’t as bad as the AZ first shot. (I believe that with AZ+AZ, the first dose’s side effects are worse than the second.) They did not compare AZ+AZ directly to AZ+Pfizer.
• The small Berlin study said basically the same thing as the tiny German study.
• The Saarland study found that the side effects of a Pfizer dose after an AZ dose were about the same as Pfizer after Pfizer.
• This study from Saarland University Medical Center with 216 vaccinees found that side effects were worse for AZ than mRNA on the first dose, but AZ+mRNA was fine and very similar to mRNA+mRNA.

Effectiveness in humans

Study	against	1st Dose	2nd Dose	Effectiveness
Sweden	symptomatic infection	AZ	Pfizer	67%
Sweden	symptomatic infection	AZ	Moderna	79%
Sweden	symptomatic infection	AZ	AZ	50%
Sweden	symptomatic infection	Pfizer	Pfizer	78%
Sweden	symptomatic infection	Moderna	Moderna	87%
BC	infection	Pfizer	Pfizer	91%
BC	infection	Moderna	Moderna	92%
BC	infection	AZ	AZ	72%
BC	infection	AZ	mRNA	91%
BC	Delta infection	Pfizer	Pfizer	92%
BC	Delta infection	Moderna	Moderna	93%
BC	Delta infection	AZ	AZ	70%
BC	Delta infection	AZ	mRNA	91%
BC	hospitalization	Pfizer	Pfizer	98%
BC	hospitalization	Moderna	Moderna	98%
BC	hospitalization	AZ	AZ	93%
BC	hospitalization	AZ	mRNA	99%
BC	Delta hospitalization	Pfizer	Pfizer	98%
BC	Delta hospitalization	Moderna	Moderna	98%
BC	Delta hospitalization	AZ	AZ	93%
BC	Delta hospitalization	AZ	mRNA	99%

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This study from France didn’t give vaccine effectiveness numbers, but reported that people with Pfizer+Pfizer were twice as likely to get infected as those with AZ+Pfizer. That’s a lot!

Note, however, that the first Pfizer dose was only four weeks before the second dose, while the first AZ dose was twelve weeks before the second dose.

Boosters

This study from the US looked at antibody levels after a booster (e.g. a third shot after two doses of Spikevax), mixing and matching the brands of the boosters. The gamma globulin serum binding antibody levels (in Binding Antibody Units/mL) 15 days after the booster, in International Units per microlitre were:

	J&J primary	Spikevax primary	Comirnaty primary
J&J booster	326.0	3029.4	1904.7
Spikevax booster	3203.1	6799.8	6155.0
Comirnaty booster	2549.5	5195.6	3409.1

The study authors said basically that mixing was good, but looking at this table, my conclusion is that Spikevax (Moderna) is good. Note, however, that this study was done with a full dose of Spikevax, not the half-dose booster that Moderna is requesting authorization for.

Other tables — for the neutralizing antibody titres, for measurements at different times after the booster — showed similar results.

Note that the authors disclosed some pretty significant limitations on the study: it was small — they say too small to compare between groups — and not randomized. So don’t bet the farm based on this study.