Mixing the RotaTeq and Rotarix rotavirus vaccines schedules resulted in noninferior immunogenicity compared with using only one vaccine schedule, found a new multicenter, open-label study. Safety profiles were also similar among mixed-vaccine and single-vaccine groups, according to Dr. Romina Libster of Vanderbilt University, Nashville, Tenn., and her associates.
“These encouraging data are supported by an earlier study involving precursors of both vaccines and natural rotavirus infections,” wrote Dr. Libster and her colleagues online (Pediatrics. 2016 Jan 28. doi: 10.1542/peds.2015-2603).
The researchers randomly assigned 1,393 healthy infants who were between 6 and 14 weeks old to receive one of five different rotavirus vaccine schedules. The children, enrolled from March 2011 through September 2013, either received all doses from one vaccine or a mixture of the two different rotavirus vaccines, concurrently with other routine immunizations, accordingly:
• 244 children received three doses of RotaTeq (RV5), a live, oral vaccine containing a combination of five human-bovine reassortant rotaviruses.
• 330 children received two doses of Rotarix (RV1), a live-attenuated human rotavirus vaccine from a single human strain.
• 250 children received one dose of RotaTeq, followed by two doses of Rotarix.
• 240 children received two consecutive doses of RotaTeq followed by a dose of Rotarix.
• 329 children received one dose of Rotarix, followed by two consecutive doses of RotaTeq.
Among the 1,236 infants remaining in the study at follow-up, 77%-96% of them across the study groups attained seropositivity defined as IgA greater than or equal to 20 U/mL against at least one vaccine antigen 1 month after the last vaccine dose. Each of the mixed schedules was noninferior to each of the single-vaccine–type schedules.
In fact, a significantly greater proportion of infants receiving one Rotarix vaccine dose followed by two RotaTeq doses achieved seropositivity against both WC3 and 89-12, compared with those receiving two Rotarix doses. Similarly, infants receiving two doses of RotaTeq and one dose of Rotarix (in either order) had higher average titers against WC3 and 89-12 than infants in either of the single-vaccine groups.
“As this study was not aimed to evaluate vaccine efficacy and there is a gap of knowledge regarding a precise correlate of protection for rotavirus vaccine, the clinical relevance of the differences in immunogenicity is unclear,” the authors wrote.
No significant differences in rates of fever, diarrhea, or vomiting occurred when comparing the RV5-RV1-RV1 and RV5-RV5-RV1 groups to the single RotaTeq (RV4) group. The RV1-RV5-RV5 group, however, showed significantly more fever and vomiting than did the single Rotarix group.
“However, when the associations between group and presence of solicited symptoms were stratified by vaccine dose, there were no statistically significant differences between the two groups for the first or second doses of rotavirus vaccine,” the authors wrote.
The most commonly reported adverse event was irritability. Of 70 infants hospitalized during the study, only one case was linked to the vaccine: a 2-month-old girl receiving two doses of Rotarix and diagnosed after the first dose with gastroenteritis concurrent with an Escherichia coli urinary tract infection. Among 33 infants with bloody stools across the groups, 14 cases were determined to have been related to the vaccine. One case of intussusception occurring 91 days after the last dose was classified as unrelated to the vaccine.
The research was funded by the National Institute of Allergy and Infectious Diseases, the National Institutes of Health, and the US Department of Health and Human Services. Dr. Libster and her colleagues all reported some kind of relationship with a variety of companies including Merck, Novartis, bioCSL, and others. Dr. Turley also holds publicly traded Abbott and Pfizer stock, and Ms. McNeal has laboratory service agreements with Merck and GSK.