405. Serum Antibody Responses Against Carbapenem-Resistant Klebsiella pneumoniae in Infected Patients

BACKGROUND: Capsular polysaccharide (CPS) of Carbapenem-resistant K. pneumoniae ST258 (CR-Kp) is a potential vaccine target. CPS of these isolates generally falls within 2 homology groups named clade 1 and clade 2. We and others have made antibodies (Abs) that act against clade2 CR-Kp but failed to make therapeutic Abs against clade1 CR-Kp. Previous studies had shown that studying patient’s antibody responses could help in identifying suitable candidates for developing immunotherapies. Thus, we sought to identify potential vaccine candidates by investigating the humoral response CPS in CR-Kp-infected patients. METHODS: 24 CR-Kp isolates and corresponding serums were collected from inpatients at Stony Brook Hospital. CPS was isolated and purified by size-exclusion column chromatography from CR-Kp strains 34 (clade 2), 36 (clade 1), and 38 (clade-Other). Anti-CPS Abs in patient’s serum were detected by enzyme-linked immunosorbent assay (ELISA) and bulk Abs from positive serum were purified using an affinity column. These Abs were tested for activity against CR-Kp by serum bactericidal and agglutination assays. RESULTS: 50% of clade2 CR-Kp-infected patients had humoral responses against CPS34. 77% of clade 1-infected patients sera cross-reacted wtih CPS34, but none of them developed Abs against CPS36. Interestingly, 90% of clade1 and 60% of clade 2-infected patients, respectively, showed Abs binding to CPS38. Thus, we selectively purified Anti-CPS Abs from two clade-Other-infected patients and observed that they were cross-reactive with all three CPS. Further, these Anti-CPS Abs agglutinated all tested CR-Kp isolates (34, 36, and 38) when compared with control human IgG (P < 0.005). Additionally, these Anti-CPS Abs promoted killing of clade2 bacteria and inhibited the growth of clade1 bacteria in Ab-mediated serum bactericidal assay. These data elucidate that humoral responses developed in clade-Other CR-Kp-infected patients have therapeutic potential. CONCLUSION: With the unavailability of effective antimicrobials for CR-Kp, approaches like developing novel anti-CPS vaccine could serve as an alternate therapy. Our data suggest that developing immunotherapies targeting CPS38 could potentially provide protection across both clade1 and clade2 bacteria in clinical settings. DISCLOSURES: All authors: No reported disclosures.