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.

Japhet Adomako Anim, Opokua Ofori-Anyinam, Tsiri Agbenyega, Seth Owusu-Agyei, Lode Schuerman, Pascale Vandoolaeghe, Frank Prempeh, Elvis Ato Wilson, Harry Owusu-Boateng, David Sambian, David Dosoo, Emilia Gvozdenovic, Albert Agordo Dornudo, Elisha Adeniji, Kwaku Poku Asante, Yaw Ntiamoah, Samuel Benard Ekow Harrison, Clara Agutu, Theresa Maria Rettig, Owusu Boahen, Patrick Boakye Yiadom Buabeng, Prince Agyapong Darko, Lydia Nana Badu, Marc Lievens, Samuel Adjei, Seyram Kaali, Daniel Ansong

Journal: Vaccine 2021;38(18):3411-3421

PMID: 32192811

Free Full Text on PubMed Central View on PubMed

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.

Address: Kintampo Health Research Center, Ghana Health Service, PO Box 200, Kintampo, Ghana. Electronic address: [email protected].; Kwame Nkrumah University of Science & Technology/Agogo Presbyterian Hospital, P.O. Box 27 Agogo, Asante Akyem, Ghana.; Kintampo Health Research Center, Ghana Health Service, PO Box 200, Kintampo, Ghana. Electronic address: [email protected].; GSK Vaccines, Avenue Fleming 20, 1300 Wavre, Belgium. Electronic address: [email protected].; Kintampo Health Research Center, Ghana Health Service, PO Box 200, Kintampo, Ghana. Electronic address: [email protected].; Kintampo Health Research Center, Ghana Health Service, PO Box 200, Kintampo, Ghana. Electronic address: [email protected].; GSK Vaccines, Avenue Fleming 20, 1300 Wavre, Belgium. Electronic address: [email protected].; Kintampo Health Research Center, Ghana Health Service, PO Box 200, Kintampo, Ghana. Electronic address: [email protected].; Kintampo Health Research Center, Ghana Health Service, PO Box 200, Kintampo, Ghana. Electronic address: [email protected].; Kintampo Health Research Center, Ghana Health Service, PO Box 200, Kintampo, Ghana. Electronic address: [email protected].; GSK Vaccines, Avenue Fleming 20, 1300 Wavre, Belgium.; Kintampo Health Research Center, Ghana Health Service, PO Box 200, Kintampo, Ghana. Electronic address: [email protected].; Kintampo Health Research Center, Ghana Health Service, PO Box 200, Kintampo, Ghana. Electronic address: [email protected].; GSK Vaccines, Avenue Fleming 20, 1300 Wavre, Belgium. Electronic address: [email protected].; GSK Vaccines, Avenue Fleming 20, 1300 Wavre, Belgium. Electronic address: [email protected].; Kintampo Health Research Center, Ghana Health Service, PO Box 200, Kintampo, Ghana; London School of Hygiene and Tropical Medicine, UK; University of Health and Allied Sciences, Ho, Ghana. Electronic address: [email protected].; Kwame Nkrumah University of Science & Technology/Agogo Presbyterian Hospital, P.O. Box 27 Agogo, Asante Akyem, Ghana. Electronic address: [email protected].; GSK Vaccines, Avenue Fleming 20, 1300 Wavre, Belgium. Electronic address: [email protected].

DOI: 10.1016/j.vaccine.2020.03.014

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MeSH Terms: Child, Child, Preschool, Ghana, Humans, Infant, Malaria Vaccines, Measles, Rubella, Yellow Fever Vaccine