One-month evaluation of safety and immunogenicity of a Vi-DT typhoid conjugate vaccine (Bio-TCV®) in Indonesian subjects 6 months to 45 years: A phase III randomized clinical trial
Bernie Endyarni Medise,
I. Gusti Ayu Trisna Windiani,
Dominicus Husada,
Rini Sekartini,
Hartono Gunardi,
Angga Wirahmadi,
Dwiyanti Puspitasari,
Leny Kartina,
I. Gusti Agung Ngurah Sugitha Adnyana,
I. Gusti Lanang Sidiartha,
I. Made Dwi Lingga Utama,
I. Ketut Agus Somia,
Iris Rengganis,
Sukamto Koesnoe,
Hindra Irawan Satari,
Soedjatmiko Soedjatmiko,
Sri Rezeki Hadinegoro,
Ismoedijanto Ismoedijanto,
Parwati Setiono Basuki,
Gatot Soegiarto,
Soetjiningsih Soetjiningsih,
Rini Mulia Sari,
Mita Puspita,
Aria Kekalih,
Sreshta Mukhi,
Vianca Samara Andhary,
Novilia Sjafri Bachtiar,
Sushant Sahastrabuddhe
Affiliations
Bernie Endyarni Medise
Department of Child Health, Faculty of Medicine University of Indonesia, Dr. Cipto Mangunkusumo General National Hospital, Jakarta, Indonesia; Corresponding author at: Child Health Department, Faculty of Medicine University of Indonesia, Jalan Diponegoro No 71, Jakarta 10340, Indonesia.
I. Gusti Ayu Trisna Windiani
Department of Child Health, Faculty of Medicine Udayana University, RSUP Prof. dr. I.G.N.G. Ngoerah Denpasar, Bali, Indonesia
Dominicus Husada
Department of Child Health, Faculty of Medicine Airlangga University, RS. Dr. Soetomo, Surabaya, Indonesia
Rini Sekartini
Department of Child Health, Faculty of Medicine University of Indonesia, Dr. Cipto Mangunkusumo General National Hospital, Jakarta, Indonesia
Hartono Gunardi
Department of Child Health, Faculty of Medicine University of Indonesia, Dr. Cipto Mangunkusumo General National Hospital, Jakarta, Indonesia
Angga Wirahmadi
Department of Child Health, Faculty of Medicine University of Indonesia, Dr. Cipto Mangunkusumo General National Hospital, Jakarta, Indonesia
Dwiyanti Puspitasari
Department of Child Health, Faculty of Medicine Airlangga University, RS. Dr. Soetomo, Surabaya, Indonesia
Leny Kartina
Department of Child Health, Faculty of Medicine Airlangga University, RS. Dr. Soetomo, Surabaya, Indonesia
I. Gusti Agung Ngurah Sugitha Adnyana
Department of Child Health, Faculty of Medicine Udayana University, RSUP Prof. dr. I.G.N.G. Ngoerah Denpasar, Bali, Indonesia
I. Gusti Lanang Sidiartha
Department of Child Health, Faculty of Medicine Udayana University, RSUP Prof. dr. I.G.N.G. Ngoerah Denpasar, Bali, Indonesia
I. Made Dwi Lingga Utama
Department of Child Health, Faculty of Medicine Udayana University, RSUP Prof. dr. I.G.N.G. Ngoerah Denpasar, Bali, Indonesia
I. Ketut Agus Somia
Department of Internal Medicine, Faculty of Medicine Udayana University, RSUP Sanglah Denpasar, Bali, Indonesia
Iris Rengganis
Department of Internal Medicine, Faculty of Medicine University of Indonesia, Dr. Cipto Mangunkusumo General National Hospital, Jakarta, Indonesia
Sukamto Koesnoe
Department of Internal Medicine, Faculty of Medicine University of Indonesia, Dr. Cipto Mangunkusumo General National Hospital, Jakarta, Indonesia
Hindra Irawan Satari
Department of Child Health, Faculty of Medicine University of Indonesia, Dr. Cipto Mangunkusumo General National Hospital, Jakarta, Indonesia
Soedjatmiko Soedjatmiko
Department of Child Health, Faculty of Medicine University of Indonesia, Dr. Cipto Mangunkusumo General National Hospital, Jakarta, Indonesia
Sri Rezeki Hadinegoro
Department of Child Health, Faculty of Medicine University of Indonesia, Dr. Cipto Mangunkusumo General National Hospital, Jakarta, Indonesia
Ismoedijanto Ismoedijanto
Department of Child Health, Faculty of Medicine Airlangga University, RS. Dr. Soetomo, Surabaya, Indonesia
Parwati Setiono Basuki
Department of Child Health, Faculty of Medicine Airlangga University, RS. Dr. Soetomo, Surabaya, Indonesia
Gatot Soegiarto
Department of Internal Medicine, Faculty of Medicine Airlangga University, RS. Dr. Soetomo, Surabaya, Indonesia
Soetjiningsih Soetjiningsih
Department of Child Health, Faculty of Medicine Udayana University, RSUP Prof. dr. I.G.N.G. Ngoerah Denpasar, Bali, Indonesia
Rini Mulia Sari
PT. Bio Farma, Bandung, Indonesia
Mita Puspita
PT. Bio Farma, Bandung, Indonesia
Aria Kekalih
Community Medicine Department, Faculty of Medicine University of Indonesia, Dr. Cipto Mangunkusumo General National Hospital, Jakarta, Indonesia
Sreshta Mukhi
Department of Child Health, Faculty of Medicine University of Indonesia, Dr. Cipto Mangunkusumo General National Hospital, Jakarta, Indonesia
Vianca Samara Andhary
Department of Child Health, Faculty of Medicine University of Indonesia, Dr. Cipto Mangunkusumo General National Hospital, Jakarta, Indonesia
Novilia Sjafri Bachtiar
PT. Bio Farma, Bandung, Indonesia
Sushant Sahastrabuddhe
International Vaccine Institute, Seoul, Republic of Korea
Background: Typhoid fever typically affects children and young adults and is a considerable cause of morbidity and mortality. Vaccination is the most effective preventive strategy to control typhoid fever in the short to medium term. However, in most endemic countries do not have a typhoid vaccine that is suitable for children below 2 years old. Methods: This is a randomized, observer blinded phase III trial using Vi-DT typhoid conjugate vaccine and an already WHO licensed prequalified (PQed) typhoid conjugate vaccine (Typbar TCV) as control. About 936 healthy subjects were recruited and divided into 3 age groups: infants group aged 6–24 months, children group aged 2–11 years, adolescents and adults group aged 12–45 years, and followed up till 28 days post vaccination. Blood sample was taken at pre-vaccination and at 28th day post vaccination to evaluate immunogenicity. Results: The most common immediate local reaction was pain in all age groups, followed by redness. The most common immediate systemic reaction in the infant group was irritability while in the adults and children group was muscle pain. The intensity of reactions was mostly mild and moderate. Severe reactions were in the form of pain and fever. Reactions mostly resolved within 48 h. Seroconversion at 28 days in the Vi-DT group was higher in both adults and children compared to the PQed typhoid conjugate vaccine, Typbar-TCV (p = 1.000; p = 0.250), respectively. The Geometric Mean Titer (GMT) in the Vi-DT group was higher in adults (p = 0134), whereas the PQed typhoid conjugate vaccine Typbar-TCV demonstrated a higher GMT in children and infants (p = 0.277; p = 0.884), respectively. Conclusion: Vi-DT typhoid conjugate vaccine (Bio-TCV®) is safe and immunogenic in subjects 6 months to 45 years old.Clinical trial registration number.NCT04051268, registration date: 09/08/2019.
