Human systemic and mucosal immune responses support further exploration of a Klebsiella pneumoniae protein-based vaccine

Background: Neonatal sepsis caused by Klebsiella pneumoniae is a major cause of under-five mortality in sub-Saharan Africa, and the rapid increase of infections caused by bacteria resistant to most or all available antimicrobials severely limits treatment options. An effective, maternally-administered vaccine could make a substantial reduction in neonatal sepsis and associated negative outcomes, as well as reduce the overall need for antimicrobials, a key driver of antimicrobial resistance. This exploratory, hypothesis-generating pilot study investigated the potential for a maternally administered protein-based vaccine to provide neonatal protection via antibodies transferred transplacentally and through breastfeeding. 

Methods: A case-control pilot study of mother and baby dyads was designed with 20 neonates developing K. pneumoniae sepsis and 95 uninfected control neonates to analyse breastmilk IgA, cord blood IgG and maternal serum IgA and IgG antibodies on a protein microarray, and case isolates were whole-genome sequenced. 

Results: Following computational analyses to identify surface-exposed candidates, we generated a protein microarray with 161 selected K. pneumoniae proteins representing 152 unique genes. The analysis of breastmilk IgA, cord blood IgG and maternal serum IgA and IgG identified a set of proteins eliciting antibody responses, some correlated with lack of K. pneumoniae sepsis which could indicate the presence of potentially protective antibodies. 

Conclusions: This is an essential first step in exploring surface protein accessibility, despite the large capsule. We highlight fimbrial structures, conjugative pili, and small lipoproteins associated with large outer membrane complexes as potential protein vaccine targets.