Fifteen years of experience with the oral live-attenuated human rotavirus vaccine: reflections on lessons learned

Abstract

Introduction: Rotavirus (RV) disease remains a prominent cause of disease burden in children <5 years of age worldwide. However, implementation of RV vaccination has led to significant reductions in RV mortality, compared to the pre-vaccination era. This review presents 15 years of real-world experience with the oral live-attenuated human RV vaccine (HRV; Rotarix). HRV is currently introduced in ≥80 national immunization programs (NIPs), as 2 doses starting from 6 weeks of age. Areas covered: The clinical development of HRV and post-marketing experience indicating the impact of HRV vaccination on RV disease was reviewed. Expert opinion: In clinical trials, HRV displayed an acceptable safety profile and efficacy against RVgastroenteritis, providing broad protection against heterotypic RV strains by reducing the consequences of severe RV disease in infants. Real-world evidence shows substantial, rapid reduction in the number of RV infections and associated hospitalizations following introduction of HRV in NIPs, regardless of economic setting. Indirect effects against RV disease are also observed, such as herd protection, decrease in nosocomial infections incidence, and a reduction of disease-related societal/ healthcare costs. However, not all countries have implemented RV vaccination. Coverage remains suboptimal and should be improved to maximize the benefits of RV vaccination.

Review of Over 15 Years Postmarketing Safety Surveillance Spontaneous Data for the Human Rotavirus Vaccine (Rotarix) on Intussusception

“…The benefits of RV vaccines have been well documented in prelicensure clinical efficacy studies and numerous postlicensure vaccine effectiveness and impact studies conducted in different parts of the world [ 41 ]. These benefits include impact on diarrhoea-related deaths, hospitalisations, and other health outcomes associated with RV gastroenteritis and may also go beyond reducing RV gastroenteritis-related mortality and morbidity (e.g., reduced incidence of childhood seizures [ 67 ] and improved hospital quality of care [ 68 ]).…”

“…A favourable benefit–risk balance for HRV has been suggested in various studies [ 35 , 38 – 40 ]. However, the concern of IS occurring in temporal association with immunisation subsequent to the findings in 1999, among other reasons, has led to some hesitancy in the implementation of the RV vaccines in national immunisation programmes [ 41 ]. Continuous postmarketing surveillance is important for monitoring this safety concern, especially for the newly introduced RV vaccines, to provide real-time safety data for such less frequent events that are difficult to observe in prelicensure clinical trials or postmarketing data with a small proportion of the exposed population analysed.…”

Established and new rotavirus vaccines: a comprehensive review for healthcare professionals

“… 17 , 38 , 87 HRV is currently registered worldwide in >100 countries and is WHO prequalified. 35 , 88 The vaccine is administered in 2 doses between the ages of 6 and 24 weeks. 19…”

“…This includes data in pre-term, low birth weight infants, and other at-risk populations such as human immunodeficiency-virus (HIV)-infected or malnourished children. 13 , 36 , 38 , 88 , 95 , 113–120 In contrast, to date, many of the locally marketed or recently launched vaccines have a limited record of efficacy and/or effectiveness data in global settings. Some of these vaccines with limited global experience data, namely 116E and BRV-PV (both locally manufactured), have received WHO prequalification, allowing accelerated introduction of RV vaccination in high-mortality countries (with the additional support of GAVI, PATH, and UNICEF).…”

Defining the Recipe for an Optimal Rotavirus Vaccine Introduction in a High-Income Country in Europe

“…For each percentage point increase in herd effect, the reduction in the cannibalising effect of the secondary infection sources was 1.06 percentage points. The cannibalising effect of secondary sources of infection on herd effect in RotaBIS was estimated at 35% in the second year of observation, reaching 0% when the maximum herd effect was attained [37].…”