AUTHOR=Kapulu Melissa C. , Muthumbi Esther , Otieno Edward , Rossi Omar , Ferruzzi Pietro , Necchi Francesca , Acquaviva Alessandra , Martin Laura B. , Orindi Benedict , Mwai Kennedy , Kibet Hillary , Mwanzu Alfred , Bigogo Godfrey M. , Verani Jennifer R. , Mbae Cecilia , Nyundo Christopher , Agoti Charles N. , Nakakana Usman Nasir , Conti Valentino , Bejon Philip , Kariuki Samuel , Scott J. Anthony G. , Micoli Francesca , Podda Audino 

TITLE=Age-dependent acquisition of IgG antibodies to Shigella serotypes—a retrospective analysis of seroprevalence in Kenyan children with implications for infant vaccination

JOURNAL=Frontiers in Immunology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1340425

DOI=10.3389/fimmu.2024.1340425

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>Shigellosis mainly affects children under 5 years of age living in low- and middle-income countries, who are the target population for vaccination. There are, however, limited data available to define the appropriate timing for vaccine administration in this age group. Information on antibody responses following natural infection, proxy for exposure, could help guide vaccination strategies.</p></sec><sec><title>Methods</title><p>We undertook a retrospective analysis of antibodies to five of the most prevalent <italic>Shigella</italic> serotypes among children aged &lt;5 years in Kenya. Serum samples from a cross-sectional serosurvey in three Kenyan sites (Nairobi, Siaya, and Kilifi) were analyzed by standardized ELISA to measure IgG against <italic>Shigella sonnei</italic> and <italic>Shigella flexneri</italic> 1b, 2a, 3a, and 6. We identified factors associated with seropositivity to each <italic>Shigella</italic> serotype, including seropositivity to other <italic>Shigella</italic> serotypes.</p></sec><sec><title>Results</title><p>A total of 474 samples, one for each participant, were analyzed: Nairobi (<italic>n</italic> = 169), Siaya (<italic>n</italic> = 185), and Kilifi (<italic>n</italic> = 120). The median age of the participants was 13.4 months (IQR 7.0–35.6), and the male:female ratio was 1:1. Geometric mean concentrations (GMCs) for each serotype increased with age, mostly in the second year of life. The overall seroprevalence of IgG antibodies increased with age except for <italic>S. flexneri</italic> 6 which was high across all age subgroups. In the second year of life, there was a statistically significant increase of antibody GMCs against all five serotypes (<italic>p</italic> = 0.01–0.0001) and a significant increase of seroprevalence for <italic>S. flexneri</italic> 2a (<italic>p</italic> = 0.006), <italic>S. flexneri</italic> 3a (<italic>p</italic> = 0.006), and <italic>S. sonnei</italic> (<italic>p</italic> = 0.05) compared with the second part of the first year of life. Among all possible pairwise comparisons of antibody seropositivity, there was a significant association between <italic>S. flexneri</italic> 1b and 2a (OR = 6.75, 95% CI 3–14, <italic>p</italic> &lt; 0.001) and between <italic>S. flexneri</italic> 1b and 3a (OR = 23.85, 95% CI 11–54, <italic>p</italic> &lt; 0.001).</p></sec><sec><title>Conclusion</title><p>Children living in low- and middle-income settings such as Kenya are exposed to <italic>Shigella</italic> infection starting from the first year of life and acquire serotype-specific antibodies against multiple serotypes. The data from this study suggest that <italic>Shigella</italic> vaccination should be targeted to infants, ideally at 6 or at least 9 months of age, to ensure children are protected in the second year of life when exposure significantly increases.</p></sec>