A Study of Intranasal Live Attenuated Influenza Vaccine Immunogenicity and Associations With the Nasopharyngeal Microbiome Among Children in the Gambia

Summary

The live attenuated influenza vaccine (LAIV) is made up of weakened influenza viruses given into the nose and in early studies was shown to be better than the standard influenza vaccine at preventing infections in children. However, more recently, it has performed less well and it may also work less well in Sub-Saharan Africa. Not only do the investigators not know why this is, but the investigators also do not fully understand why LAIV produces stronger nasal antibody responses in some individuals but not others. Usually harmless bacteria that are present in participants noses can influence how our immune system works and variations in these may explain differences in how LAIV works. The project will recruit children given LAIV in the Gambia to gain further understanding of these issues. The investigators will measure a variety of responses to LAIV, including genes that can change their expression early after vaccination and use advanced computational techniques to identify new relationships between these genes and other LAIV responses. The investigators will also see whether nasal bacterial profiles in children who respond to LAIV are different from those who do not. In addition, the investigators will alter these bacteria in a subset of children with antibiotics and see whether this affects both nasal gene expression and later responses to LAIV.

Timeline

Start

2017-01-30

Primary completion

2018-12-19

Completion

2019-05-23

Publications

• Peno C, Jagne YJ, Clerc M, Balcazar Lopez C, Armitage EP, Sallah H, Drammeh S, Senghore E, Goderski G, van Tol S, Meijer A, Ruiz-Rodriguez A, de Steenhuijsen Piters WAA, de Koff E, Jarju S, Lindsey BB, Camara J, Bah S, Mohammed NI, Kampmann B, Clarke E, Dockrell DH, de Silva TI, Bogaert D. Interactions between live attenuated influenza vaccine and nasopharyngeal microbiota among children aged 24-59 months in The Gambia: a phase 4, open-label, randomised controlled trial. Lancet Microbe. 2025 Mar;6(3):100971. doi: 10.1016/j.lanmic.2024.100971. Epub 2025 Jan 17.
• Keeley AJ, Groves D, Armitage EP, Senghore E, Jagne YJ, Sallah HJ, Drammeh S, Angyal A, Hornsby H, de Crombrugghe G, Smeesters PR, Rossi O, Carducci M, Peno C, Bogaert D, Kampmann B, Marks M, Shaw HA, Turner CR, de Silva TI. Streptococcus pyogenes Colonization in Children Aged 24-59 Months in the Gambia: Impact of Live Attenuated Influenza Vaccine and Associated Serological Responses. J Infect Dis. 2023 Oct 3;228(7):957-965. doi: 10.1093/infdis/jiad153.
• Peno C, Armitage EP, Clerc M, Balcazar Lopez C, Jagne YJ, Drammeh S, Jarju S, Sallah H, Senghore E, Lindsey BB, Camara J, Bah S, Mohammed NI, Dockrell DH, Kampmann B, Clarke E, Bogaert D, de Silva TI. The effect of live attenuated influenza vaccine on pneumococcal colonisation densities among children aged 24-59 months in The Gambia: a phase 4, open label, randomised, controlled trial. Lancet Microbe. 2021 Dec;2(12):e656-e665. doi: 10.1016/S2666-5247(21)00179-8.
• Lindsey BB, Jagne YJ, Armitage EP, Singanayagam A, Sallah HJ, Drammeh S, Senghore E, Mohammed NI, Jeffries D, Hoschler K, Tregoning JS, Meijer A, Clarke E, Dong T, Barclay W, Kampmann B, de Silva TI. Effect of a Russian-backbone live-attenuated influenza vaccine with an updated pandemic H1N1 strain on shedding and immunogenicity among children in The Gambia: an open-label, observational, phase 4 study. Lancet Respir Med. 2019 Aug;7(8):665-676. doi: 10.1016/S2213-2600(19)30086-4. Epub 2019 Jun 21.
• Armitage EP, Camara J, Bah S, Forster AS, Clarke E, Kampmann B, de Silva TI. Acceptability of intranasal live attenuated influenza vaccine, influenza knowledge and vaccine intent in The Gambia. Vaccine. 2018 Mar 20;36(13):1772-1780. doi: 10.1016/j.vaccine.2018.02.037. Epub 2018 Feb 23.

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