Vaccine 31 (2013) 1100– 1105Contents lists available at SciVerse ScienceDirectVaccinej ourna l ho me pag e: www.elsevier.com/locate/vaccineA phase I clinical trial of a new 5-valent rotavirus vaccineExpedito J.A. Lunaa,∗, Neuza M. Frazatti-Gallinab, Maria C.S.T. Timenetskyc, Maria R.A. Cardosod,Maria A.S.M. Verase, João L. Miragliab, Ana M.U. Escobarf, Sandra J.F.E. Grisif, Isaias Rawb,Alexander R. Preciosob,faInstituto de Medicina Tropical, Universidade de São Paulo, BrazilbInstituto Butantan, Secretaria de Estado da Saúde de São Paulo, BrazilcInstituto Adolfo Lutz, Secretaria de Estado da Saúde de São Paulo, BrazildDepartamento de Epidemiologia, Faculdade de Saúde Pública, Universidade de São Paulo, BrazileFaculdade de Ciências Médicas da Santa Casa de São Paulo, BrazilfDepartamento de Pediatria, Faculdade de Medicina, Universidade de São Paulo, Brazila r t i c l e i n f oArticle history:Received 19 September 2012Received in revised form 6 December 2012Accepted 8 December 2012Available online 20 December 2012Keywords:RotavirusVaccineClinical trialSafetyImmunogenicitya b s t r a c tWe conducted a phase I, double-blind, placebo-controlled trial to evaluate a new 5-valent oral rotavirusvaccine’s safety and immunogenicity profiles. Subjects were randomly assigned to receive 3 orally admin-istered doses of a live-attenuated human-bovine (UK) reassortant rotavirus vaccine, containing five viralantigens (G1, G2, G3, G4 and G9), or a placebo. The frequency and severity of adverse events were assessed.Immunogenicity was evaluated by the titers of anti-rotavirus IgA and the presence of neutralizing anti-bodies anti-rotavirus. No severe adverse events were observed. There was no difference in the frequencyof mild adverse events between experimental and control groups. The proportion of seroconversion wasconsistently higher in the vaccine group, for all serotypes, after each one of the doses. The 5-valent vac-cine has shown a good profile of safety and immunogenicity in this small sample of adult volunteers.© 2012 Elsevier Ltd. 1. IntroductionNew generation rotavirus vaccines were licensed in thebeginning of 2006 [1]. Since then, both Merck’s pentavalent human-bovine reassortant vaccine (RotaTeq®) and GSK’s monovalentattenuated human vaccine (Rotarix®) have been widely used. Sev-eral studies have shown a reduction in rotaviral gastroenteritisor diarrhea incidence and mortality following vaccine introduc-tion [2–4]. In 2009, the World Health Organization recommendedthe introduction of rotavirus vaccines into national immunizationprograms for controlling rotavirus gastroenteritis [5]. However,vaccines prices still represent a hurdle in the expansion of theiruse [6,7].The Instituto Butantan, one of the Brazilian public vaccine man-ufacturers, is participating in an international effort to develop anew rotavirus vaccine. An agreement between Path Foundation andInstituto Butantan has made possible the technology transfer forthe production of the UK-based reassortant tetravalent rotavirusvaccine, with financial support from the Bill & Melinda Gates∗Corresponding author.E-mail addresses: eluna@usp.br, expedito luna@uol.com.br (E.J.A. Luna).Foundation. The Instituto Butantan has added an additionalserotype to the vaccine, G9, as this is one of the most prevalent inBrazil [8]. It is expected that this new vaccine, that includes the mostfrequent serotypes found in Brazil, will contribute to the reduc-tion of the burden of rotavirus disease in Brazil and elsewhere, ata reduced cost. Being a public, not for profit vaccine manufacturer,Butantan considers its mission to produce immunobiologicals forthe Brazilian National Immunization Program at lower prices thanthe market.Brazil introduced the monovalent attenuated human rotavirusvaccine (Rotarix®) in its universal vaccination program in 2007.Vaccine coverage has been above 80% in all years since the introduc-tion (CM Domingues, head of the Brazilian National ImmunizationProgram, personal communication). The persistence of detectionof some rotavirus genotypes among Brazilian infants, such as G2P[4], suggests that the vaccine currently in use might be less effica-cious against certain rotavirus serotypes [9–11]. This would be anadditional reason for the development of new vaccines.In 1999, the first rotavirus vaccine was withdrawn from the mar-ket because of an increased risk of intussusception among vaccinerecipients. As a result, the new generation vaccines were evaluatedin trials with large sample sizes powered to detect an increasedrisk for intussusception, which was not observed [11–13]. Recent0264-410X © 2012 Elsevier Ltd. http://dx.doi.org/10.1016/j.vaccine.2012.12.020Open access under the Elsevier OA license.Open access under the Elsevier OA license.
