Randomized, controlled trial of the long term safety, immunogenicity and efficacy of RTS,S/AS02D malaria vaccine in infants living in a malaria-endemic region
| Autor: | Thomas Aebi, Mwanajaa Shomari, Joe Cohen, Grace Mwangoka, Marie-Claude Dubois, Amanda J. Leach, Marc Lievens, Nahya Salim, Marcel Tanner, David Schellenberg, Hassan Mshinda, Johan Vekemans, Sulende Kubhoja, Francisca Machera, Ali Mohammed, Tonya Villafana, Terrell Carter, Omar Juma, W. Ripley Ballou, Salim Abdulla, Richard Kamata |
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| Jazyk: | angličtina |
| Předmět: |
Male
HBsAg Pediatrics Endemic Diseases Antibodies Protozoan Antibodies Viral Tanzania 0302 clinical medicine Medicine Drug Interactions 030212 general & internal medicine Haemophilus Vaccines Vaccines 0303 health sciences education.field_of_study Malaria vaccine Vaccination Falciparum Immunogenicity 3. Good health Infectious Diseases Female Safety Infants medicine.drug medicine.medical_specialty Hepatitis B vaccine lcsh:Arctic medicine. Tropical medicine Efficacy lcsh:RC955-962 Population lcsh:Infectious and parasitic diseases 03 medical and health sciences Double-Blind Method RTS S/AS02 Malaria Vaccines parasitic diseases Humans lcsh:RC109-216 Hepatitis B Vaccines education Diphtheria-Tetanus-Pertussis Vaccine 030304 developmental biology business.industry Research RTS S Infant Vaccine efficacy Malaria EPI Pertussis vaccine Parasitology business |
| Zdroj: | Malaria Journal Malaria Journal, Vol 12, Iss 1, p 11 (2013) |
| ISSN: | 1475-2875 |
| DOI: | 10.1186/1475-2875-12-11 |
| Popis: | Background The RTS,S/AS malaria candidate vaccine is being developed with the intent to be delivered, if approved, through the Expanded Programme on Immunization (EPI) of the World Health Organization. Safety, immunogenicity and efficacy of the RTS,S/AS02D vaccine candidate when integrated into a standard EPI schedule for infants have been reported over a nine-month surveillance period. This paper describes results following 20 months of follow up. Methods This Phase IIb, single-centre, randomized controlled trial enrolled 340 infants in Tanzania to receive three doses of RTS,S/AS02D or hepatitis B vaccine at 8, 12, and 16 weeks of age. All infants also received DTPw/Hib (diphtheria and tetanus toxoids, whole-cell pertussis vaccine, conjugated Haemophilus influenzae type b vaccine) at the same timepoints. The study was double-blinded to month 9 and single-blinded from months 9 to 20. Results From month 0 to 20, at least one SAE was reported in 57/170 infants who received RTS,S/AS02D (33.5%; 95% confidence interval [CI]: 26.5, 41.2) and 62/170 infants who received hepatitis B vaccine (36.5%; 95% CI: 29.2, 44.2). The SAE profile was similar in both vaccine groups; none were considered to be related to vaccination. At month 20, 18 months after completion of vaccination, 71.8% of recipients of RTS,S/AS02D and 3.8% of recipients of hepatitis B vaccine had seropositive titres for anti-CS antibodies; seroprotective levels of anti-HBs antibodies remained in 100% of recipients of RTS,S/AS02D and 97.7% recipients of hepatitis B vaccine. Anti-HBs antibody GMTs were higher in the RTS,S/AS02D group at all post-vaccination time points compared to control. According to protocol population, vaccine efficacy against multiple episodes of malaria disease was 50.7% (95% CI: -6.5 to 77.1, p = 0.072) and 26.7% (95% CI: -33.1 to 59.6, p = 0.307) over 12 and 18 months post vaccination, respectively. In the Intention to Treat population, over the 20-month follow up, vaccine efficacy against multiple episodes of malaria disease was 14.4% (95% CI: -41.9 to 48.4, p = 0.545). Conclusions The acceptable safety profile and good tolerability of RTS,S/AS02D in combination with EPI vaccines previously reported from month 0 to 9 was confirmed over a 20 month surveillance period in this infant population. Antibodies against both CS and HBsAg in the RTS,S/AS02D group remained significantly higher compared to control for the study duration. Over 18 months follow up, RTS,S/AS02D prevented approximately a quarter of malaria cases in the study population. Clinical trials Gov identifier: NCT00289185 |
| Databáze: | OpenAIRE |
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