New Rotavirus Vaccines

Abstract

The twin objectives of all vaccines are safety and efficacy. In the case of rotavirus vaccine for humans safety and efficacy initially was sought through oral administration of related viruses indigenous to animals but the assumption that these viruses are harmless to humans appeared to be only partly correct. Furthermore the efficacy of the animal viruses in protection against human rotavirus infection and disease was inconsistent. The double-stranded RNA genome of rotaviruses is segmented which allowed reassortment in coinfected cell cultures with dsRNA segments of human rotaviruses. The animal rotavirus backbone was supposed to guarantee attenuation whereas the genes for G and P surface proteins from human viruses were supposed to provide efficacy. In 1998 the U.S. Food and Drug Administration (FDA) licensed a quadrivalent rotavirus vaccine containing reassortants of a G serotype 3 rhesus rotavirus (RRV) and rotavirus genes for human serotypes G1 2 and 4 proteins. Unfortunately these viruses multiplied well in the gastrointestinal tract and retained the ability to cause fever and diarrhea in some infants. More important suspicions that were engendered before licensure concerning an association of the vaccine with intussusception were confirmed postlicensure by case clusters in the 2 weeks after vaccination.1 RRV was withdrawn from use in 1999. (excerpt)