written by Tara Haelle

Two different rotavirus vaccines have been licensed by the FDA: RotaTeq and Rotarix. Both of these came after Rotashield, an earlier vaccine that lasted barely over a year on the market before it was pulled because it led to a bowel obstruction disorder called intussusception in about 1-2 out of 10,000 infants. (RotaTeq and Rotarix also increase the risk of intussusception, which I explain in detail here, but the risk is lower.)

It’s not unusual for different companies to make vaccines for the same disease, but RotaTeq and Rotarix have slightly different schedules too: RotaTeq is given in three doses, and Rotarix is given in two doses. But if a doctor runs out of the brand your child got last time when you come in for the next well visit, is it safe to mix and match the two? That’s what a new study investigated.

With the exception of influenza vaccines, which have a lot of different options, most parents probably don’t spend a lot of time researching individual types of the same vaccine, such as Daptacel, the DTaP vaccine manufactured by Sanofi, versus Infanrix, the DTaP vaccine manufactured by GlaxoSmithKline. (If you’re interested, you can find a full list of all the different vaccine brand names and what they contain at this CDC page.)

For the most part, your child receives whatever your doctor stocks. And, for the most part, there aren’t many significant differences between brands in terms of the way the vaccine is made. Some brands may contain slightly different components than another — which might be relevant if your child has a very specific known allergy to a particular brand’s ingredient — but the vaccines are generally pretty similar.

RotaTeq and Rotarix have pretty different manufacturing processes, however. Both are live oral vaccines, but they use different components of the actual virus to induce immunity. RotaTeq, licensed in 2006 to Merck, is pentavalent, which means it uses five reassorted human and cow rotaviruses mixed together. Children receive the first dose between 6-15 weeks old and should get the two additional doses by 8 months old. Rotarix, licensed in 2008 to GlaxoSmithKline, is monovalent, made from a single human strain of rotavirus. Its first dose is also recommended between 6-15 weeks with the second dose given by 8 months old. It’s worth noting that the introduction of these vaccines has gone far in reducing rotavirus infections and has boosted herd immunity against the disease.

The vaccines prevented any rotavirus gastroenteritis in about 74% to 87% of the infants in the clinical trials, and they prevented severe gastroenteritis in 85% to 98%. The CDC Advisory Committee on Immunization Practices recommends that children receive either a full schedule of RotaTeq or a full schedule of Rotarix, but this might not always be possible, especially if a child moves to a different practice or is at a small practice with a small stock of vaccines on hand. In fact, one recent study found that about 3% of children get a combination of the two vaccines.

So this new study tested how three different mix-and-match schedules of the two vaccines compared to a straight-RotaTeq and a straight Rotarix schedule in terms of immune response and safety. The study was funded by the National Institutes of Health and the U.S. Department of Health and Human Services, and it took place at ten different sites in the country*.

The study was not blinded, so the doctor and parent knew which one the child was getting, but the 1,393 children enrolled in it were randomly assigned to one of five groups:

244 children received 3 doses of RotaTeq (RV5-RV5-RV5)

330 children received 2 doses of Rotarix (RV1-RV1)

250 children received one dose of RotaTeq followed by two doses of Rotarix (RV5-RV1-RV1)

240 children received two consecutive doses of RotaTeq followed by a dose of Rotarix (RV5-RV5-RV1)

329 children received one dose of Rotarix followed by two consecutive doses of RotaTeq (RV1-RV5-RV5)

Then one month after each child received their last vaccine dose, the researchers tested antibodies levels (titers) in their blood. If they had at least 20 U/mL of IgA, a specific type of antibody, against at least one of the antigens (rotavirus pieces), they were considered seropositive (their body developed immunity against rotavirus).

Overall, 77% to 96% of the infants had sufficient levels to one or more antigens across the five groups without huge differences. The most notable difference was that the effectiveness of Rotarix alone was a fair bit lower than the other combinations. What the study was officially testing was whether mixing and matching the two brands would be “non-inferior” to solely receiving RotaTeq or solely receiving Rotarix. The study was not testing the effectiveness of RotaTeq or Rotarix alone, so for the purposes of this particular study’s research question, the lower effectiveness seen with Rotarix is not relevant for the conclusion. Since parents might want to know the particulars, however, here’s how each group stacked up:

Antigen (WC3) Antigen (89–12) Both antigens Either antigen Group 1 (RV5-RV5-RV5) 90% 77% 77% 91% Group 2 (RV5-RV1-RV1) 88% 89% 86% 91% Group 3 (RV5-RV5-RV1) 90% 85% 85% 91% Group 4 (RV1-RV1) 67% 76% 66% 77% Group 5 (RV1-RV5-RV5) 93% 91% 89% 96%

But Is It Safe?

And what about safety? The mixing and matching did not increase side effects compared to receiving just RotaTeq or just Rotarix. The rates of fever, diarrhea, and vomiting were in a similar range across all groups (see chart below). The most common adverse event reported was irritability.

During the course of the study, 70 of the babies (5%) were hospitalized for some reason, but only one of these was determined to be related to the vaccine. That case was a 2-month-old girl who spent two days in the hospital five days after her first dose for gastroenteritis. She had an E. coli urinary tract infection at the same time, and she recovered from both with no problems.

In addition, 33 total infants (2%) had bloody stools during the study, and 14 of these (1% of the total group) were determined to be related to the vaccine. One infant had intussusception three months after the last dose, but it was determined not to be related to the vaccine.

Fever Diarrhea Vomiting Any symptom Bloody stool Group 1 (RV5-RV5-RV5) 15% 9% 10% 27% 2 infants Group 2 (RV5-RV1-RV1) 15% 11% 9% 29% 1 infants Group 3 (RV5-RV5-RV1) 13% 7% 8% 24% 2 infants Group 4 (RV1-RV1) 9% 9% 5% 20% 2 infants Group 5 (RV1-RV5-RV5) 15% 10% 10% 29% 7 infants

What Else to Know?

One weakness of this study is that it only looked at titers. It did not track the children over the next several years to see how many of them ended up getting rotavirus, so it cannot tell us what the exact real-world effectiveness of the different combinations are. However, the fact that the level of immunity induced by each mix-and-match group was at least as much (or more) than the levels of the individual vaccines means that each of the different combinations probably offers a very similar amount of protection from the disease. Another weakness of the study is that the researchers could not confirm without any doubt that none of the infants got rotavirus during the course of the study. If they did, that could affect what their antibodies levels were, but it’s unlikely that very many would have had it.

The bottom line: if your doctor or several different doctors mix and match RotaTeq and Rotarix doses, your child will be just as protected as if they had received only one or another, and they won’t be at risk for any more side effects.

*The ten sites included Children’s Hospital of Oakland in California; Children’s Mercy Hospital in Kansas City, Missouri; Duke University Health System in Durham, North Carolina; Emory University School of Medicine in Atlanta; Group Health Cooperative in Seattle; St Louis University in St Louis; University of Iowa in Iowa City; University of Maryland in Baltimore; University of Texas Medical Branch at Galveston; and Vanderbilt University Medical Center in Nashville.