The human rotavirus serotypes (G1, G2, G3, G4 and P1) have been selected for RotaTeq because these strains caused over 90% of rotavirus disease in North America, Europe and Australia over 88% of rotavirus disease worldwide between 1973 and 2003.
Efficacy: The efficacy of RotaTeq was evaluated in 2 studies among infants who received the vaccine (n=3484) or placebo (n=3499). The 3rd dose was administered to infants as old as 32 weeks of age. Efficacy evaluations included efficacy against any severity (mild, moderate and severe) of rotavirus gastroenteritis and efficacy against severe rotavirus gastroenteritis. The effect on healthcare contacts for rotavirus gastroenteritis, including hospitalizations and emergency department visits (n=68,038), routine visits to a physician (n=5673) and work loss (n=68,038) was also evaluated in the rotavirus safety and efficacy trial (REST). Concomitant administration of other licensed childhood vaccines except for oral poliovirus vaccine (OPV) was permitted in all phase III studies.
Efficacy against any severity of gastroenteritis caused by naturally occurring rotavirus of the composite of the G serotypes (G1-G4) included in RotaTeq was 73.8% and efficacy against severe rotavirus gastroenteritis was 98.2% through the 1st rotavirus season after completion of vaccination. RotaTeq also provided protection against non-vaccine G serotypes. Based on limited data, the efficacy against any severity of gastroenteritis caused by the non-vaccine G serotype (G9) was 74.1%. The efficacy of RotaTeq through 2 rotavirus seasons after completion of vaccination against any severity of rotavirus gastroenteritis was 71.3%.
RotaTeq reduced the rate of hospitalizations, emergency department visits, non-urgent care visits and parent/legal guardian work loss days. Hospitalizations and emergency department visits were evaluated among 68,038 infants and non-urgent care visits were evaluated among 5673 infants for a maximum of 2 years after vaccination. The rate reductions were as follows: 94.5% for hospitalizations and emergency department visits (95.8% for hospitalizations and 93.7% for emergency department visits), 86% for non-urgent care visits and 86.6% for parent/legal guardian work loss days.
Efficacy of RotaTeq against rotavirus gastroenteritis through the 1st full rotavirus season after completion of vaccination and reduction in hospitalizations/emergency department visits for rotavirus gastroenteritis for up to 2 years postvaccination by G-serotype are shown in Table 1.
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Efficacy and Safety in Pre-Term Infants:
RotaTeq or placebo was administered to 2070 pre-term infants (25-36 weeks gestational age), including 1007 recipients of RotaTeq, according to their chronological age in a placebo-controlled study. Among a subset of 308 pre-term infants who were followed for all adverse experiences, the safety profile was generally similar among those infants receiving RotaTeq as compared with those receiving placebo. The incidence of fever, vomiting, diarrhea or irritability was generally similar among vaccine and placebo recipients. Efficacy (70.3%) in a subset of 204 pre-term infants (153 evaluable) was generally similar in the overall population.
Studies with Other Vaccines:
The immunogenicity of RotaTeq, and diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccine, inactivated poliovirus vaccine (IPV), Haemophilus influenzae
type b conjugate vaccine (HIB), hepatitis B vaccine and pneumococcal conjugate vaccine was evaluated among 1358 infants. The immune responses to the specified vaccines were largely unaffected by RotaTeq. Of the 17 antigens studied, the antibody responses were similar among vaccine and placebo recipients except for a slightly diminished response to 1 of the 3 antigens tested for pertussis (pertactin). In addition, the studies demonstrated the efficacy of RotaTeq (89.5%) when administered with these vaccines.
Concomitant administration of RotaTeq and OPV did not affect the immune response to the polio antigens in a controlled study of 735 vaccinated infants. Although concomitant administration of OPV reduced some immune responses to RotaTeq, the seroconversion rates (greater than or equal to 3-fold rise from baseline) for serum IgA were >93%. There is evidence that a high level of efficacy against severe rotavirus gastroenteritis is maintained. The immune responses to RotaTeq are unaffected when OPV is administered 2 weeks after RotaTeq.
The safety profile, including the incidences of fever, vomiting, diarrhea and irritability was generally similar among subjects receiving the specified concomitant vaccines with RotaTeq and subjects receiving the specified concomitant vaccines with placebo.
In 1 study, 7367 infants received a hexavalent (DTaP, IPV, HIB and hepatitis B) vaccine concomitantly with RotaTeq. The frequency of overall serious adverse experiences (SAEs), regardless of causal relationship, was 2.9% in recipients of RotaTeq and 3.2% in placebo recipients. More detailed safety information was evaluated among a subset of 638 infants receiving RotaTeq with a hexavalent vaccine. The safety profile, including the incidences of fever, vomiting, diarrhea and irritability was generally similar among subjects receiving a hexavalent vaccine with RotaTeq and subjects receiving a hexavalent vaccine with placebo.
The immunologic mechanism by which RotaTeq protects against rotavirus gastroenteritis is unknown. A relationship between antibody responses to RotaTeq and protection against rotavirus gastroenteritis has not been established. However, RotaTeq induces antibodies that neutralize serotypes G1, G2, G3, G4 and P1. In phase III studies, 92.9-100% of recipients of RotaTeq achieved a significant rise in serum anti-rotavirus IgA after a 3-dose regimen.
Toxicology: Animal Toxicology:
A single and repeated dose oral toxicity study in mice suggests no special hazard to humans. The dose administered to mice was approximately 2.79 x 108
infectious units per kg (about 14-fold the projected infant dose).