The rotavirus vaccine story: a clinical investigator's view.

Abstract

* Abbreviations: FDA = : Food and Drug Administration • ACIP = : Advisory Committee on Immunization Practices • CDC = : Centers for Disease Control and Prevention • AAP = : American Academy of Pediatrics • VAERS = : Vaccine Adverse Events Reporting System Withdrawal of the tetravalent rhesus-human reassortant rotavirus vaccine from our arsenal of vaccines to prevent childhood diseases was a major disappointment. However, the experience demonstrated that the mechanisms established to monitor vaccine safety in the United States functioned effectively. This article reviews how the association with intussusception was discovered and evaluated, and speculates about lessons learned and how to use them. Prelicensure clinical evaluation of the rhesus-human reassortant vaccine was a process that lasted >15 years, cost hundreds of millions of dollars, involved multiple governmental agencies, industry, and dozens of clinical investigators. It was given to >10 000 infants in 27 clinical trials conducted in 9 different countries. After this large and lengthy experience the vaccine was submitted to the Food and Drug Administration (FDA) for consideration for licensure. Concurrently, a Rotavirus Working Group of the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) was established to review the safety, immunogenicity, and efficacy of the vaccine to propose recommendations for its use. This working group was composed of experts in pediatric infectious disease, vaccinology, epidemiology, and public health. As part of the review process, a member of the ACIP Working Group reviewed all serious adverse events reported in all of the industry-sponsored trials of all of the rhesus rotavirus vaccine candidates and noted 5 cases of intussusception among 10 054 vaccinees, 3 of which occurred during the week postvaccination, and 1 case among 4633 placebo recipients. None of these cases had been judged by the clinical study investigators to be attributable to the vaccine. The vaccinees with intussusception had participated in 5 different trials and had received 3 different rhesus rotavirus vaccine preparations (rhesus-human reassortant serotype 1 vaccine, tablet preparation of the tetravalent rhesus-human reassortant vaccine, and the subsequently licensed lyophilized tetravalent rhesus-human reassortant vaccine, …