Mitsunobu Miyazu1, Hitoshi Kikuchi2, Atsuo Hamada3, Shinji Fukushima4, Kazunobu Ouchi5, Valerie Bosch Castells6, Hanako Mihara7, Marie-Claude Bonnet8. 1. Meitetsu Hospital, Sako, Nishi-ku, Nagoya-Shi, Aichi, Japan. Electronic address: mmiyazu@meitetsu-hpt.jp. 2. Meitetsu Hospital, Sako, Nishi-ku, Nagoya-Shi, Aichi, Japan. Electronic address: hkikuchi@meitetsu-hpt.jp. 3. Tokyo Medical University Hospital, Nishi-Shinjuku, Shinjuku-Ku, Tokyo, Japan. Electronic address: a-hamada@tokyo-med.ac.jp. 4. Tokyo Medical University Hospital, Nishi-Shinjuku, Shinjuku-Ku, Tokyo, Japan. Electronic address: fuku789@tokyo-med.ac.jp. 5. Kawasaki Medical School, Matsushima 577, Kurashiki-Shi, Okayama, Japan. Electronic address: kouchi@med.kawasaki-m.ac.jp. 6. Sanofi Pasteur, Marcy l'Etoile, France. Electronic address: valerie.boschcastells@sanofipasteur.com. 7. Sanofi K.K., Tokyo, Japan. Electronic address: hanako.mihara@sanofi.com. 8. Sanofi Pasteur, Marcy l'Etoile, France. Electronic address: marieclaudebonnet38@gmail.com.
Abstract
BACKGROUND: Although typhoid fever is rare in Japan, imported cases have been reported occasionally in travelers returning from endemic areas. To achieve licensing of a typhoid Vi polysaccharide vaccine (Typhim Vi(®)) and make it widely available in Japan, this study was conducted at the request of the Japanese Ministry of Health Labor and Welfare to assess the immunogenicity and safety of this vaccine when given as a single dose (the recommended schedule of administration) in a Japanese population. METHODS: In this multi-center, open-label, non-comparative, intervention study performed in Japan, 200 healthy volunteers (188 adults [≥ 18 years of age], 7 adolescents [12-17 years of age] and 5 children [2-11 years of age]) were administered Typhim Vi(®). Immunogenicity was assessed 28 days after vaccinations using an ELISA method of anti-Vi antibody detection. A 4-fold increase in anti-Vi titer was considered as the threshold for seroconversion for anti-Vi antibodies. Safety was assessed up to 28 days following vaccination. RESULTS: Overall, 92.0% (95% confidence interval [CI]: 87.3-95.4%) of participants achieved seroconversion 28 days after a single dose of typhoid Vi polysaccharide vaccine. GMTs of Vi antibody titers increased from 6.6 (95% CI: 5.8-7.4) prior to vaccination to 157.3 (95% CI: 135.1-183.2) on Day 28 after vaccination. The geometric mean of individual anti-Vi antibody titer ratios (Day 28/Day 0) was 23.9 (95% CI: 20.3-28.3). There were no immediate adverse events and no adverse events led to the discontinuation of participants from the study. Across all age groups, pain and myalgia were the most frequently reported injection site and systemic reactions, respectively. Most of these reactions were mild in intensity and resolved within 7 days. CONCLUSIONS: A single dose of typhoid Vi polysaccharide vaccine, Typhim Vi(®), demonstrated good safety and immunogenicity profile in a Japanese population.
BACKGROUND: Although typhoid fever is rare in Japan, imported cases have been reported occasionally in travelers returning from endemic areas. To achieve licensing of a typhoid Vi polysaccharide vaccine (Typhim Vi(®)) and make it widely available in Japan, this study was conducted at the request of the Japanese Ministry of Health Labor and Welfare to assess the immunogenicity and safety of this vaccine when given as a single dose (the recommended schedule of administration) in a Japanese population. METHODS: In this multi-center, open-label, non-comparative, intervention study performed in Japan, 200 healthy volunteers (188 adults [≥ 18 years of age], 7 adolescents [12-17 years of age] and 5 children [2-11 years of age]) were administered Typhim Vi(®). Immunogenicity was assessed 28 days after vaccinations using an ELISA method of anti-Vi antibody detection. A 4-fold increase in anti-Vi titer was considered as the threshold for seroconversion for anti-Vi antibodies. Safety was assessed up to 28 days following vaccination. RESULTS: Overall, 92.0% (95% confidence interval [CI]: 87.3-95.4%) of participants achieved seroconversion 28 days after a single dose of typhoid Vi polysaccharide vaccine. GMTs of Vi antibody titers increased from 6.6 (95% CI: 5.8-7.4) prior to vaccination to 157.3 (95% CI: 135.1-183.2) on Day 28 after vaccination. The geometric mean of individual anti-Vi antibody titer ratios (Day 28/Day 0) was 23.9 (95% CI: 20.3-28.3). There were no immediate adverse events and no adverse events led to the discontinuation of participants from the study. Across all age groups, pain and myalgia were the most frequently reported injection site and systemic reactions, respectively. Most of these reactions were mild in intensity and resolved within 7 days. CONCLUSIONS: A single dose of typhoid Vi polysaccharide vaccine, Typhim Vi(®), demonstrated good safety and immunogenicity profile in a Japanese population.