Efficacy of vaccination with a Klebsiella pneumoniae siderophore receptor protein vaccine for reduction of Klebsiella mastitis in lactating cattle

Abstract

Clinical mastitis caused by Klebsiella spp. is an emerging problem in the US dairy industry and results in a high degree of financial losses to dairy workers. This study was conducted as a randomized, blinded, and placebo-controlled efficacy study of a Klebsiella pneumoniae siderophore receptor protein (SRP) vaccine (Kleb-SRP), with a total of 569 cows and heifers enrolled. The study was designed to look at vaccine effect on Klebsiella mastitis; however, the SRP in Klebsiella are highly conserved across coliform bacteria, which means that the vaccine has potential for cross-protection against all coliforms. Cows were paired based on parity, days in milk at enrollment, and somatic cell count. Within pairs, individuals were randomized to receive either Kleb-SRP or a placebo formulation. Following vaccination, the incidence of Klebsiella spp. and total coliform mastitis from natural exposure were compared to determine the efficacy of the vaccine. When analyzing all cows, the reduction of mastitis risk was not significant, though milk production increased 0.31 kg/d and somatic cell counts were reduced by 20.1%. When administered before calving, the vaccine reduced the risk of Klebsiella and total coliform mastitis by 76.9 and 47.5% respectively; however, we observed no significant effect when administered after calving. The vaccine, when administered before calving, also increased milk production by an average of 1.74 kg/d and reduced somatic cell counts by 64.8%. When administered after calving, we noted a slight decrease in daily milk production (0.39 kg) but no significant effect on somatic cell counts. All cows in the study (including vaccinates and placebo) received multiple doses of a commercially available licensed Escherichia coli bacterin. It should be noted that this herd was chosen because of the high number of clinical Klebsiella clinical mastitis cases this herd experienced before the trial and the extreme environmental challenge that was present from bedding with dried manure solids. The data from this study demonstrate efficacy of the Kleb-SRP vaccine against Klebsiella mastitis alone and coliform mastitis in general (including all coliforms) when administered before the initiation of a lactation cycle.

Negatively controlled, randomized clinical trial to evaluate intramammary treatment of nonsevere, gram-negative clinical mastitis

“…These herds used bacterin core-antigen vaccines intended to reduce mastitis due to E. coli, and the recent introduction of Klebsiella-specific mastitis vaccines in the United States suggests a need to investigate the effects of immunization on the frequency of these costly negative outcomes. Gorden et al (2018) reported that a Kleb. pneumoniae siderophore receptor protein vaccine increased milk production by 1.74 kg/d and reduced SCC by 64.8% in one herd when cows were vaccinated before calving, compared with cows that did not receive the vaccine.…”

Application of TonB-Dependent Transporters in Vaccine Development of Gram-Negative Bacteria

“…A K. pneumoniae vaccine (Kleb-SRP) was prepared by purifying siderophore receptor and porin proteins from fermentation cultures of K. pneumonia. Subcutaneous vaccination of cows with Kleb-SRP before calving decreased the risk of Klebsiella and total coliform mastitis by 76.9% and 47.5%, respectively (Gorden et al, 2018).…”

“…Administration of cows with the vaccine before calving significantly decreased the risk of Klebsiella and total coliform mastitis by 76.9% and 47.5% respectively. (Gorden et al, 2018)…”

Progress towards the development of Klebsiella vaccines

“…Their preparation of DNA vaccines expressing OmpA and OmpK36 proteins protected mice, with intradermal vaccination inducing better protection than when these vaccines were given by the intramuscular (IM) route [89]. A KP siderophore receptor protein veterinary vaccine (Kleb-SRP) reduced the incidence of KP bovine mastitis and increased milk production when administered before calving [90].…”