Invasive nontyphoidal Salmonella (NTS), including Salmonella typhimurium (STm), are major yet poorly-recognized killers of infants in sub-Saharan Africa. Death in these children is usually associated with
bacteremia, commonly in the absence of gastrointestinal symptoms. Evidence from humans and animal studies suggest that severe
infection and
bacteremia occur when specific Ab is lacking. Understanding how Ab responses to Salmonella are regulated will help develop
vaccines against these devastating
infections. STm induces atypical Ab responses characterized by prominent, accelerated, extrafollicular T-independent (TI) Ab against a range of
surface antigens. These responses develop without concomitant germinal centers, which only appear as
infection resolves. Here, we show STm rapidly induces a population of TI B220(+)CD5(-) B1b cells during
infection and TI Ab from B1b cells targets the outer
membrane protein (Omp)
porins OmpC, OmpD and OmpF but not
flagellin. When
porins are used as immunogens they can ablate
bacteremia and provide equivalent protection against STm as killed
bacterial vaccine and this is wholly B cell-dependent. Furthermore Ab from
porin-immunized chimeras, that have B1b cells, is sufficient to impair
infection. Infecting with
porin-deficient bacteria identifies OmpD, a
protein absent from Salmonella Typhi, as a key target of Ab in these
infections. This work broadens the recognized repertoire of TI
protein antigens and highlights the importance of Ab from different B cell subsets in controlling STm
infection. OmpD is a strong candidate
vaccine target and may, in part, explain the lack of cross-protection between Salmonella Typhi and STm
infections.