Rotateq

The human rotavirus WI61 strain was first isolated from an 18-month-old child with gastroenteritis in Children’s Hospital of Philadelphia in 1983.^{68 (link)} Rotarix (RV1, GSK) and RotaTeq (RV5, Merck) are kindly shared by Dr. Kristen Ogden at Vanderbilt University. Murine rotavirus rD6/2-2 g strain was generated using an optimized, plasmid-based rotavirus reverse genetics system,^{69 (link)} and tested for its genetic stability, intestinal replication, and virulence. African Green Monkey kidney epithelial cell line MA104 (CRL-2378.1) was obtained from American Type Culture Collection (ATCC) and cultured in Medium 199 (Gibco) supplemented with 10% heat-inactivated fetal bovine serum (VWR), 100 units/ml penicillin and 100 μg/ml streptomycin. Rotavirus strains were propagated as described previously^{27 (link)} and the titers of virus concentrate were determined in MA104 cells using a standard plaque assay.^{70 (link)} Rotavirus inoculum was prepared by activating the stock with 5 μg/ml trypsin for 20 min at 37°C and diluting it into 50% CM with 10 μM Y-27632 up to the total volume of 100 μl, with 50 μg/ml soybean trypsin inhibitor.

Evidence for receipt of rotavirus vaccination was determined by using the Current Procedural Terminology codes 90680 and 90681 for the two rotavirus vaccines licensed in the U.S., Rotateq^® (RV5, Merck and Co, Whitehouse Station, NJ) and Rotarix^® (RV1, GSK Biologicals, Rixensart, Belgium), respectively. Vaccination coverage was calculated using a numerator of the number of enrollees with one or more claims for rotavirus vaccination prior to hospitalization and a denominator of the number of children who were age-eligible for rotavirus vaccine at the time of hospitalization for rotavirus or AGE. To be age-eligible, children were required to be at least 2 months old at the time of hospitalization and to be born after June 2006. We calculated the mean and 95% CI for vaccination coverage for all children under 60 months and stratified by age group. Vaccination coverage was compared during pre-vaccine, early vaccine, and post-vaccine biennial rotavirus seasons with Mantel-Haenszel chi-square or Fisher’s exact tests, using SAS.

Mice were vaccinated with the commercial, oral, pentavalent, and live rotavirus vaccine RotaTeq® (Merck & Co., Inc.). Two sets of experiments with different immunization protocols were used. In the first set of experiments, mice were vaccinated with 30 μl of rotavirus vaccine and 10⁸ bacterial cells or particles (high vaccine/low adjuvant immunization protocol). Mice that received only 30 μl of rotavirus vaccine were used as controls. In a second set of experiments, mice were vaccinated with 7.5 μl of rotavirus vaccine and 10⁹ bacterial cells or particles (low vaccine/high adjuvant immunization protocol). Mice that received only 7.5 μl of rotavirus vaccine were used as controls. In both protocols, mice were immunized orally on days 0, 14 and 28. Seven days after the last immunization (day 35), the specific humoral and cellular immune responses were evaluated as described below.

Based on ACIP's 2012 recommendations,²⁴ we defined vaccine completion as the accrual of the required number of doses by a specific age (8, 18, and 24 months) regardless of timing of vaccine administration. Detailed lists of doses required at 8, 18, and 24 months are presented elsewhere.²⁵ (link)
Completion of rotavirus vaccine and Haemophilus influenzae type b vaccine (Hib) doses was assessed based on the product administered. For example, a child's vaccination for rotavirus was considered complete if 2 doses of Rotarix (GSK Vaccines) or 3 doses of RotaTeq (Merck & Co., Inc.) were administered. These algorithms are detailed in the published vaccine schedule.²⁴
Although influenza and hepatitis A vaccines are also recommended by the ACIP, we did not assess them in the present study. The NIS data do not provide vaccination dates, thus we were not able to determine whether the seasonal influenza vaccine was administered during the influenza season, which is a criterion for administration. The second dose of hepatitis A vaccine should be administered between 6 and 18 months following the first dose at age 12 months or later; therefore, the second dose may be administered after 24 months—falling outside of our study period. As we could not capture appropriate completion and compliance of 2 doses of hepatitis A vaccine, it was not included in the present analysis.

Four vaccine scenarios were compared with a control (ie, no vaccine). First, vaccination with Rotarix, a live monovalent human attenuated oral rotavirus vaccine (RV1) manufactured by GlaxoSmithKline Biologicals (Belgium). Rotarix presentation is a liquid single-dose pack in a plastic tube. Two doses of Rotarix are required for full immunisation. Second, vaccination with Rotateq (for non-Gavi countries only), a live pentavalent, human–bovine reassortant vaccine (RV5) manufactured by Merck & Co (Kenilworth, NJ, USA). Rotateq presentation is a liquid single-dose pack in a plastic tube. Three doses of Rotateq are required for full immunisation. Rotateq was not considered as a comparator for the Gavi-eligible countries because the manufacturer has withdrawn supplies to Gavi countries.⁹ Third, vaccination with Rotavac, a live monovalent human-bovine liquid frozen oral rotavirus vaccine (RV1), manufactured by Bharat Biotech (Hyderabad, India). Rotavac presentation is a liquid (frozen), five-dose pack in a vial. Three doses of Rotavac are required for full immunisation. Fourth, vaccination with Rotasiil, a live pentavalent bovine-human reassortant oral rotavirus vaccine (RV5), manufactured by the Serum Institute (Pune, India). Rotasiil presentation is in lyophilised form, a two-dose pack in a vial. Three doses of Rotasiil are required for full immunisation.