Exploring the interplay between innate and adaptive immune responses to live attenuated influenza vaccine in Gambian children

Jagne, Ya Jankey (2023). Exploring the interplay between innate and adaptive immune responses to live attenuated influenza vaccine in Gambian children. PhD thesis The Open University.

DOI: https://doi.org/10.21954/ou.ro.000169f3


Influenza vaccination remains a challenge in low and middle income countries despite high rates of mortality and morbidity in children. World Health Organization and Serum Institute of India developed Nasovac-S, a single dose influenza vaccine to increase vaccine accessibility in these regions. The vaccine was trialled in some African Countries but no immunogenicity data was collected.

This thesis aimed to characterize the innate and adaptive immune responses pre and post LAIV in Gambian children and explore the relationship between the two responses post vaccination.

This study was nested within a randomised controlled trial investigating LAIV–microbiome interactions (NCT02972957) in healthy children aged 24–59 months who receive one dose of the WHO prequalified Russian-backbone trivalent LAIV containing A/17/California/2009/38 (Cal09) in 2017 and A/17/New York/15/5364 (NY15) in 2018. Cellular and humoral immune responses and phenotypes of immune cells pre and post LAIV were assessed using multi-parameter flow cytometry. Follicular helper T (Tfh) cells, were also investigated using the activation induced marker assay.

Post LAIV, decreased frequency of classical monocytes and increased frequency of intermediate monocytes in Gambian children was noted. Increased frequency of CD4+T cells but not CD8+T cells was also noted. LAIV induced bulk and influenza specific Tfh cells associated with seroconversion.

Change in the H1N1 strain of the vaccine in 2018 led to differences in viral shedding, replication and greater immunogenicity post LAIV. Further investigations determined that differences in immune responses observed between the two study vaccines were a result of a reduced replicative capacity of the pH1N1 Cal09 virus compared to pH1N1 NY15.

A single dose of LAIV in Gambian children led to perturbation of innate and adaptive immune cells post LAIV. Seroconversion post LAIV was associated with increase in frequency of intermediate monocytes and Tfh cells. Immunogenicity is also dependent on strain-selection for inclusion in influeza vaccine.

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