Abstract
Safety and protective efficacy of recombinant multi-epitope subunit vaccine (r-AK36) was evaluated in a mouse model. Recombinant AK36 protein comprised of immunodominant antigens from outer membrane proteins (Omp’s) of Klebsiella pneumoniae namely OmpA and OmpK36. r-AK36 was highly immunogenic and the hyperimmune sera reacted strongly with native OmpA and OmpK36 proteins from different K. pneumoniae strains. Hyperimmune sera showed cross-reactivity with Omp’s of other Gram-negative organisms. Humoral responses showed a Th2-type polarized immune response with IgG1 being the predominant antibody isotype. Anti-r-AK36 antibodies showed antimicrobial effect during in vitro testing with MIC values in the range of 25–50 μg/ml on different K. pneumoniae strains. The recombinant antigen elicited three fold higher proliferation of splenocytes from immunized mice compared to those with sham-immunized mice. Anti-r-AK36 antibodies also exhibited in vitro biofilm inhibition property. Subunit vaccine r-AK36 immunization promoted induction of protective cytokines IL-2 and IFN-γ in immunized mice. When r-AK36-immunized mice were challenged with 3 × LD100 dose, ∼80% of mice survived beyond the observation period. Passive antibody administration to naive mice protected them (67%) against the lethal challenge. Since the targeted OMPs are conserved among all K. pneumoniae serovars and due to the strong nature of immune responses, r-AK36 subunit vaccine could be a cost effective candidate against klebsiellosis.
Highlights
Klebsiella pneumoniae is a Gram-negative opportunistic pathogen that belongs to family Enterobacteriaceae
K. pneumoniae is recognized as a major health threat worldwide and the treatment options of Klebsiella infections are limited owing to high incidence of multiple drug resistance and adverse antibiotic reactions (Breecher, 2007; Vieira et al, 2016)
Control of K. pneumoniae is hampered by additional mechanisms such as endotoxin production that induces septic shock, capsular polysaccharide (CPS) that inhibits phagocytosis and resistance to compliment-mediated killing (Merino et al, 1992; Podschun and Ullmann, 1998; Kim et al, 2002)
Summary
Klebsiella pneumoniae is a Gram-negative opportunistic pathogen that belongs to family Enterobacteriaceae. A novel and distinct K. pneumoniae variant called hypervirulent K. pneumoniae (hvKP) has emerged which is predicted to become a major threat in Asia and Western countries (Diago-Navarro et al, 2017) Infections caused by such strains are reported to be associated with higher morbidity and mortality even with antibiotic sensitive strains. Control of K. pneumoniae is hampered by additional mechanisms such as endotoxin production that induces septic shock, CPS that inhibits phagocytosis and resistance to compliment-mediated killing (Merino et al, 1992; Podschun and Ullmann, 1998; Kim et al, 2002) This has directed attention toward controlling K. pneumoniae infections through bacterial clearance from body employing alternate strategies to improve immune defenses such as probiotics (Vieira et al, 2016) or more specific means such as vaccination and antibody therapy (Jain et al, 2015; Lee et al, 2015)
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