Immunogenicity and safety of the RTS, S/AS01 malaria vaccine co-administered with measles, rubella and yellow fever vaccines in Ghanaian children: A phase IIIb, multi-center, non-inferiority, randomized, open, controlled trial. Issue 18 (16th April 2020)

• Record Type: Journal Article
• Authors: Asante, Kwaku Poku; Ansong, Daniel; Kaali, Seyram; Adjei, Samuel; Lievens, Marc; Nana Badu, Lydia; Agyapong Darko, Prince; Boakye Yiadom Buabeng, Patrick; Boahen, Owusu; Maria Rettig, Theresa; Agutu, Clara; Benard Ekow Harrison, Samuel; Ntiamoah, Yaw; Adomako Anim, Japhet; Adeniji, Elisha; Agordo Dornudo, Albert; Gvozdenovic, Emilia; Dosoo, David; Sambian, David; Owusu-Boateng, Harry; Ato Wilson, Elvis; Prempeh, Frank; Vandoolaeghe, Pascale; Schuerman, Lode; Owusu-Agyei, Seth; Agbenyega, Tsiri; Ofori-Anyinam, Opokua
• Is Part Of: Vaccine. Volume 38:Issue 18(2020)
• Page Start: 3411
• Page End: 3421
• Publication Date: 2020-04-16
• Subjects: Non-inferiority -- RTS -- S/AS01 -- Co-administration -- Yellow fever -- Measles -- Rubella; AE adverse event -- CI confidence interval -- CS circumsporozoite -- ED50 endpoint dilution 50 -- ELISA enzyme-linked immunosorbent assay -- EPI Expanded Programme on Immunization -- EU ELISA units -- GMC geometric mean concentration -- GMT geometric mean titer -- HBs hepatitis B virus surface antigen -- IU international unit -- MR combined measles-rubella -- pIMD potential immune-mediated disease -- RCC reverse cumulative curve -- RTS, S/AS01 pre-erythrocytic Plasmodium falciparum malaria vaccine -- SAE serious adverse event -- UL upper limit -- WHO World Health Organization -- YF yellow fever; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2020.03.014
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: First RTS, S/AS01 dose was given with Vitamin A supplementation at 6 months of age. Third RTS, S/AS01 dose was given with yellow fever and measles-rubella vaccines at 9 months. Immune responses following co-administration met all non-inferiority criteria. The safety profile of the vaccines was clinically acceptable when co-administered. RTS, S/AS01 can be given with Vitamin A, yellow fever and measles-rubella vaccines. Abstract: Background: To optimize vaccine implementation visits for young children, it could be efficient to administer the first RTS, S/AS01 malaria vaccine dose during the Expanded Programme on Immunization (EPI) visit at 6 months of age together with Vitamin A supplementation and the third RTS, S/AS01 dose on the same day as yellow fever (YF), measles and rubella vaccines at 9 months of age. We evaluated the safety and immunogenicity of RTS, S/AS01 when co-administered with YF and combined measles-rubella (MR) vaccines. Methods: In this phase 3b, open-label, controlled study (NCT02699099), 709 Ghanaian children were randomized (1:1:1) to receive RTS, S/AS01 at 6, 7.5 and 9 months of age, and YF and MR vaccines at 9 or 10.5 months of age (RTS, S coad and RTS, S alone groups, respectively). The third group received YF and MR vaccines at 9 months of age and will receive RTS, S/AS01 at 10.5, 11.5 and 12.5 months of age (Control group). All children received Vitamin A at 6 months of age. Non-inferiority of immune responses to the vaccine antigens was evaluated 1 month following co-administration versus RTS, S/AS01 or EPI vaccines (YF and MR vaccines) alone using pre-defined non-inferiority criteria. Safety was assessed until Study month 4.5. Results: Non-inferiority of antibody responses to the anti-circumsporozoite and anti-hepatitis B virus surface antigens when RTS, S/AS01 was co-administered with YF and MR vaccines versus RTS, S/AS01 alone was demonstrated. Non-inferiority of antibody responses to the measles, rubella, and YF antigens when RTS, S/AS01 was co-administered with YF and MR vaccines versus YF and MR vaccines alone was demonstrated. The safety profile of all vaccines was clinically acceptable in all groups. Conclusions: RTS, S/AS01 can be co-administered with Vitamin A at 6 months and with YF and MR vaccines at 9 months of age during EPI visits, without immune response impairment to any vaccine antigen or negative safety effect.