Natural immunity to Klebsiella pneumoniae in mothers and their infants in Malawi
Nathalie Karaky, Oliver Pearse, Robert Lawrence, Emma Bownes, Edward Hildebrand, Allan Zuza, Luis Gadama, David Lissauer, Samantha Lissauer, Kondwani Kawaza, Nicholas Feasey, David GoldblattAbstract
Background
Klebsiella pneumoniae is a leading cause of neonatal sepsis in low- and middle-income countries, with high associated mortality. Anti-K. pneumoniae maternal antibodies may provide early-life protection to neonates, yet data about their prevalence, transplacental transfer, and functional activity remain limited.
Methods
We conducted a study in Malawian mother-infant dyads measuring IgG to K. pneumoniae O1 serotypes, O1αβ,2α and O1αβ,2β and functional immunity. Immunity was also analysed in dyad sera from (i) culture-confirmed K. pneumoniae infection (cases) (ii) non-K. pneumoniae infections (sick controls), (iii) healthy controls.
Results
Anti O1-IgG titres were similar in all mothers and significantly greater than those seen in infants. Similarly, functional immunity was significantly higher in mothers than their infants. Transfer ratios for functional immunity between mother and infant were significantly lower (0.017) than those seen for anti-O1 IgG (0.8). While IgG to O1αβ,2α and O1αβ,2β and functional immunity were significantly correlated in healthy infants this was not the case in maternal serum. Neither Klebsiella specific maternal IgM titres nor IgG subclasses could explain this thus additional factors in addition to anti-O1 IgG are likely contributing to functional immunity.
Conclusions
Natural anti O1 antibodies are ubiquitous in healthy mothers in Malawi and IgG is efficiently transferred to neonates. Reduced functional immunity in infants compared to mothers as demonstrated in this study may underpin the susceptibility to K. pneumoniae infection in early life justifying the exploration of maternal immunisation to prevent early life infection. Further studies are needed to define the characteristics of anti-K. pneumoniae immunity that might be associated with clinical protection.