Duration of ecacy of Ty21a, attenuated Salmonella typhi live oral vaccine Myron M. Levine a,b, *, Catterine Ferreccio c , Paulina Abrego b , Oriana San Martin b , Edith Ortiz d , Stanley Cryz e a Center for Vaccine Development, University of Maryland School of Medicine, 685 W. Baltimore St., Baltimore, MD 21201, USA b Centro para Vacunas en Desarrollo, Chile (CVD-Chile), Servicio de Salud Metropolitano Norte, Hospital Roberto del Rio, Avenida Zan Äartu 1085, Santiago, Chile c Department of Public Health, Ponti®cia Universidad Cato Âlica de Chile, Marcoleta 352, Santiago, Chile d Ministry of Health, Santiago, Chile e Swiss Serum and Vaccine Institute, P.O. Box 2707, 3001 Berne, Switzerland Abstract Currently, two dierent formulations of Ty21a live oral typhoid vaccine are commercialized. The enteric-coated capsule formulation was licensed based on results of three years of follow-up of a randomized, placebo-controlled, double-blind ®eld trial in Area Occidente, Santiago, Chile, which demonstrated that three doses of this formulation, given on an every other day immunization schedule, conferred the best protection among several options evaluated. Subsequently, a liquid formulation (lyophilized vaccine organisms reconstituted with buer and water into a vaccine cocktail) was commercialized after it was shown to provide superior protection than enteric-coated capsules over three years of follow-up in a randomized, placebo- controlled ®eld trial in Area Sur Oriente and Area Norte, Santiago. Surveillance in the Area Occidente trial was continued for four additional years (i.e., total seven years of follow-up) and in the Area Sur Oriente/Area Norte trial for two additional years (i.e., a total of ®ve years of follow-up). These additional surveillance data, which were analyzed to ascertain the longevity of protection conferred by these formulations of Ty21a, revealed that three doses of Ty21a in enteric-coated capsules (every other day schedule) conferred 67% protection over three years and 62% protection over seven years of follow-up, whereas three doses of liquid formulation (every other day schedule) elicited 77% protection over three years and 78% over ®ve years of follow-up. Based on its excellent clinical acceptability, ease of oral administration, proven practicality in school-based mass immunization, and long-term ecacy enduring at least seven years, it is proposed that school-based immunization with Ty21a be utilized as a control measure in areas where the incidence of typhoid fever is high and Salmonella typhi are antibiotic-resistant. # 1999 Elsevier Science Ltd. All rights reserved. Keywords: Typhoid fever; Vaccines; Immunization 1. Introduction Attenuated Salmonella typhi strain Ty21a, which was developed by chemical mutagenesis in the early 1970s before the recombinant DNA era [1], has earned a rightful place as a pioneer among live oral bacterial vaccines because of its remarkable track record of safety and ecacy. However, this highly attenuated live oral vaccine strain is only modestly immunogenic and controlled ®eld trials have shown that the ecacy of Ty21a is closely correlated with the speci®c formu- lation of the vaccine and the number of doses adminis- tered [2±7]. The formulation that has been most widely commercialized consists of enteric-coated (hydroxypro- phymethylcellulosephthalate-treated) capsules contain- ing 2±5 Â 10 9 colony forming units (CFU) of lyophilized vaccine organisms. These capsules are re- Vaccine 17 (1999) S22±S27 0264-410X/99/$ - see front matter # 1999 Elsevier Science Ltd. All rights reserved. PII: S0264-410X(99)00231-5 www.elsevier.com/locate/vaccine * Corresponding author.