Rotavirus vaccine efficacy: current status and areas for improvement

Carvalho, Miguel F.; Gill, Davinder

Taking into account the mortality and morbidity caused by Rotavirus infection, several vaccines were developed over the years, most of which are live attenuated variants of naturally occurring strains. These vaccines were traditionally obtained after multiple rounds of passage in cell culture such as the pioneering bovine RIT4237 that demonstrated an overall efficacy of 50% in Phase III clinical trials but was never commercialized. Later-generation vaccines included a rhesus monkeyhuman tetravalent reassortant (RRV-TV, later licensed as RotaShield and soon after removed from market due to increased risk of intussusception, a rare, painful and potentially life-threatening bowel obstruction event), a human monovalent G1P [8] (RIX4414, commercialized as Rotarix by GSK; 2 doses from 6-24 weeks), and a pentavalent bovinehuman reassortant (RV5, marketed by Merck as RotaTeq; 3 doses from 6-32 weeks 27 ). Early studies have pointed at discrepancies in vaccine efficacy while comparing results from low and high child mortality settings. [28] [29] [30] [31] [32] Overall, a metaanalysis of Rotarix and RotaTeq performance (29 and 12 trials, respectively) involving 186,263 participants in low and high child mortality settings, indicates that in low mortality regions Rotarix prevents 86% and 85% of severe RGE cases in infants under 1 and 2 years of age, respectively while RotaTeq prevents 87% and 82% of severe RGE cases in infants under 1 and 2 years of age, respectively. In high child mortality regions, Rotarix prevents 63% and 42% of severe RGE cases in infants under 1 and 2 years of age, respectively, while RotaTeq prevents 57% and 41% of severe RGE cases in infants under 1 and 2 years of age, respectively. Both vaccines are regarded as safe with no significant difference in adverse events noted between vaccine and placebo groups. Intussusception cases were 58 in 97,246 children after Rotarix and 34 in 81,459 children following RotaTeq. 5, [33] [34] [35] [36] Another example is the Lanzhou lamb Rotavirus vaccine (LLR; genotype G10P [12] ) which has been licensed in China since 2000 (one dose/year for 3 years, children 2 to 35 months old). Based on a study comprising 1,412 children immunized with at least one dose, the overall protection rate was found to be 35% (total population of 6,441 under 5 years old 37 ). Rotavin-M1 (an attenuated G1P [8] strain developed and licensed in Vietnam) was regarded as safe and had comparable seroconversion to Rotarix in clinical trials. 38 Other vaccines undergoing development, clinical trials and licensure include the naturally occurring reassortant monovalent human-bovine Rotavirus vaccine 116E (Rotavac, by Bharat Biotech International, strain G9P [11] ). In a Phase III clinical trial the vaccine was administered at 6, 10 and 14 weeks of age (4,532 vaccine and 2,267 placebo) and based on observations up to 2 years of age, efficacy against severe RGE was 55.1%. There were 8 and 3 intussusception cases for vaccine and placebo groups, respectively (p = 0.7613). 39 Another vaccine under evaluation is a pentavalent bovinehuman reassortant vaccine developed by the Serum Institute of India (BRV-PV, comprising serotypes G1, G2, G3, G4 and G9). A clinical trial taking place in Niger used a 3 dose regimen at 6, 10, 14 weeks of age for a cohort 1,780 and 1,728 infants in vaccine and placebo groups, respectively. The authors reported a 66.7% efficacy against severe RGE with no cases of intussusception. 40 It is important to