No abstract

Typhoid is still prevalent in many parts of the world. We reviewed all published and unpublished studies of a newly licensed vaccine composed of the Vi capsular polysaccharide of Salmonella typhi, the causative agent of the disease, which had been licensed previously outside the United States. These included observational studies and double-blind randomized studies done in the United States, Europe, and the developing world in which children and adults unexposed to typhoid or those living in endemic areas were enrolled. A single dose of 25 micrograms of the purified polysaccharide was given by intramuscular injection. The vaccine was well tolerated, inducing only minor reactions in fewer than 10% of subjects. An antibody response occurred in about 90% of subjects and lasted about 3 years. Seroconversion was shown in children as young as 2 years. Protective efficacy was evaluated in two studies conducted in areas in which typhoid is endemic; the efficacy was 55% and 75%, respectively, in adults and in children older than 5 years. The Vi vaccine compares favorably with other typhoid vaccines in regard to safety, patient compliance, immunogenicity, and efficacy. Vi polysaccharide is a well-standardized antigen that is effective in a single parenteral dose, is safer than whole-cell vaccine, and may be used in children 2 years of age or older.

AbstrakDua pendekatan yang saling melengkapi pada saat ini dikembangkan untuk memperbaiki dan meningkatknn penggunakan vaksin Vi poLisakarida kapsul (CPS). Dilakuknn studi vaksin konjugat yang terdiri clari V digabung dengan toxoi1 tetanus murni (Vi-TT) pacta percobaan fase I pada 52 orang dewasa, umur I 9-3 3 tahun. Dua injeksi ( There was no sertous adverse event af'ter any of the injections. Anti-Vi antibody let,els, measurecl by raclio-immunoassay (RIA) before ancl I weeks after first injection, indicated that all subjects in the V-TT group were seroprotectecl (>-I 1t"g/ml) after vaccination, comparecl to 88'57o of those who received Vi alone. Seroconversion , defined by 4-fold increase over baseline of total serLtm anti-V, was achieved by 80.7Vo of V-TT vaccinees afier the first injection, increasing to 84.67o after the second injection, comparecl to 73.0Vo anct 69.2% with Vi olone. As anticipated, the second dose of V|-TT did not eticit a booster response. After the secontl dose of vaccine, signfficantly higher antibody titres were found in the V-TT group (GMT 6.8 St"g/ml) comparecl with the Typhim V@ group (GMT 3.0 1t g/ml). Typhoict Four weeks after injection, 90.9Vo of enrolled subject seroconverted for anti-V antibotly (4-fold increase), ancl B6.4Vo were consklerecl seroprotected (2 I 1t'g/ml). The anti-Vi antibody GMTvalue (RIA) increased from 0.15 p.g/mt before vaccination to 2.04 1tg/ml. Serological resub of initially HAV-negative subjects were satisfactory, with a anti-HAv Lntibody GMT (moclifiecl RIA) of 176.g 1t g/mt four weeks afrer injection, and all subjects being seroprotected (2 20 1tg/ml). In the coming years, we can look forward to important advances in the clevelopment of these new vaccines that wiII be of benefit to both children and aclults living in countries endemic for these iùfectious diseases.

Melanjutkan suatu penelitian klinis yang luas yang dilakukan secara randomized double-blind tentang polisakaricla kapsul. Vi ttersus plasebo pada tahun 1985, kami telah dapat meneliti 83 individu l0 tahun kemudian. Mereka berumur 15 sampai l8 tahyn, dan antibodi terhadap Vi diukur secara radtoimunoassay pada 40 orang yang sebelumnya mendapat vaksin tifuicl dan pacla 43 orang yang mendapat kontrol polisakarida kapsul meningokokus. Proporsi anak-anak dengan antibodi di atas tingkat yang dianggap protektif> I 1tg/ml adalah 58q(; di kedua kelompok. Proporsi anak-anak dengan antibodi V2 I 1tg/ml pada kelompokvaksinasi Vi mirip tlengan hasil penelitian pada anak-anak ini 3 tahun setelah imunisasi. Proporsi anak-anak dengan antibodi protektif pacla kelompok kontrol bertambah secara bermakna 7 tahun kemudian, anak-anak ini tinggal di daerah endemis. Data ini menunjukkan bahwa vaksin Vi mungkin masih protektif 10 tahun setelah vaksinasi, namun paparan yang terus menerus pada demam tifuid menimbulkan tingkat antibod.i protektif yang bermakna pada anak-anak usia 1 5-18 tahun yang tidak divaksinasi. Penelitian ini menunjukkan bahwa antibodi Vi umumnya tinggi patla orang yang tinggal di daerah endemik tifuid dan tidak berhubungan dengan infeksi baru atau karier kronis. Perlu penelitian lebih lanjut tentang imunogenitas jangka panjang vaksinasi V di daerah non-endemik.