High diversity of Escherichia coli causing invasive disease in neonates in Malawi poses challenges for O-antigen based vaccine approach

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Abstract Escherichia coli is an important cause of neonatal sepsis and the third most prevalent cause of neonatal infection in sub-Saharan Africa, often with negative outcomes. Development of maternally administered vaccines is under consideration, but to provide adequate protection, an understanding of serotypes causing invasive disease in this population is essential. We describe the genomic characteristics of a collection of neonatal E. coli isolates from a tertiary hospital in Blantyre, Malawi, with specific reference to potential protection by vaccines under development. Neonatal blood or cerebrospinal fluid cultures from 2012-2021 identified 205 E. coli isolates, and 170 could be recovered for sequencing. There was very high diversity in sequence types, LPS O-antigen-type and fimbrial H-type, which all showed temporal fluctuations and previously undescribed diversity, including ten putative novel O-types. Vaccines in clinical trials target the O-antigen but would only protect against one third (33.7%) of neonatal sepsis cases in this population (EXPEC9V, in clinical trials). An O-antigen based vaccine would require 30 different O-types to protect against 80% of infections. Vaccines against neonatal sepsis in Africa are of considerable potential value, but their development requires larger studies to establish the diversity and stability over time of relevant O-types for this population. Data summary All sequencing data is freely available under the sequencing project IDs ERP120687 (short read data; accessions in Supplementary Table 1) and PRJNA1121524 (long-read data; accessions in Supplementary Table 2), detailed per-isolate information is provided in Supplementary Table 3. Blood culture and CSF data used to show the trends and numbers of E. coli cases per year is available in Supplementary Table 4.

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