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.

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.

• Authors: Kwaku Poku Asante, Daniel Ansong, Seyram Kaali, Samuel Adjei, Marc Lievens, Lydia Nana Badu, Prince Agyapong Darko, Patrick Boakye Yiadom Buabeng, Owusu Boahen, Theresa Maria Rettig, Clara Agutu, Samuel Benard Ekow Harrison, Yaw Ntiamoah, Japhet Adomako Anim, Elisha Adeniji, Albert Agordo Dornudo, Emilia Gvozdenovic, David Dosoo, David Sambian, Harry Owusu-Boateng, Elvis Ato Wilson, Frank Prempeh, Pascale Vandoolaeghe, Lode Schuerman, Seth Owusu-Agyei, Tsiri Agbenyega, Opokua Ofori-Anyinam
• Journal: Vaccine (Vaccine) Vol. 38 Issue 18 Pg. 3411-3421 (04 16 2020) ISSN: 1873-2518 [Electronic] Netherlands
• PMID: 32192811 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Ltd. All rights reserved.

Chemical References

• Malaria Vaccines
• Yellow Fever Vaccine

Topics

• Child
• Child, Preschool
• Ghana
• Humans
• Infant
• Malaria Vaccines (adverse effects)
• Measles
• Rubella (prevention & control)
• Yellow Fever Vaccine (adverse effects)