Selective Protective Potency of Yersinia pestis ΔnlpD Mutants

Abstract

It has recently been shown that the NlpD lipoprotein is essential to Yersinia pestis virulence and that subcutaneous administration of the nlpD mutant could protect mice against bubonic and pneumonic plague better than the EV vaccine strain [PLoS One 2009. V. 4. № 9. e7023]. In this study, similar ΔnlpD mutants were generated on the basis of other Y. pestis parent strains, including strains from the subspecies microtus, which is avirulent to guinea pigs and humans. Comparative testing confirmed that immunization of mice with ΔnlpD mutants induces immunity 105 times more potent than the one induced by the administration of the EV vaccine strain. At the same time, NlpD- bacteria failed to protect guinea pigs in the case of a subcutaneous challenge with Y. pestis, inducing a 106 times less potent protection compared with that conferred by immunization with the EV vaccine strain. The possible causes of the observed phenomena are discussed.

Plague vaccine: recent progress and prospects

“…Lipoprotein NlpD of Y. pestis is an essential virulence factor for the development of bubonic and pneumonic plague. 53,54 Subcutaneous administration of the Δ nlpD Y. pestis Kimberley53 mutant conferred protection to mice against bubonic and pneumonic plague better than the EV76 vaccine strain. 53 Dentovskaya et al generated a variety of Δ nlpD mutant strains based on three Yersinia parental strains (i.e., subsp.…”

“…In comparison to the reference vaccine strain EV NIIEG, immunization with the Δ nlpD mutant strains provided potent protective immunity against plague in BALB/c mice challenged with 200 LD 100 of virulent Y. pestis 231 strain, but failed to do so in the guinea pig model. 54 The intrinsic reasons are not clear yet, but the inconsistent protection observed in different animal models diminishes the possibility of Δ nlpD Y. pestis mutant as one of the live plague vaccine candidates.…”

“…microtus bv. aitaica) and provided potent immunity against plague in the mouse model), but failed to do so in the guinea pig model 54 Y. pestis CO92 Δ rbsA Δ lsrA 80–100% of female Swiss Webster mice surviving a challenge dose of 8- to 50-LD 50 equivalent of WT CO92NDND 55 Y. pestis CO92 Δ lpp Δ msbB Δ ail or Δ lpp Δ msbB::ailL2 >2.5 × 10 6 CFU by s.c. infection and >5 × 10 6 CFU CFU by i.n. infection female Swiss Webster micei.m.…”

Plague Vaccines: Status and Future

“…Of note, a Y. pestis ΔyopH mutant is attenuated and provides a high level of protection against bubonic and pneumonic plague in mice [133]. Studies showed that Δpcm and ΔnlpD mutants were attenuated and elicited protective immunity in mice [134, 135], but the immunization with ΔnlpD mutants failed to protect guinea pigs [136]. …”

Host Iron Nutritional Immunity Induced by a Live Yersinia pestis Vaccine Strain Is Associated with Immediate Protection against Plague

“…At the same time, Y. pestis has been recognized as a Tier 1 select biological agent due to its potential use as a bioweapon (Inglesby et al, 2000 ). The severity of the disease in combination with concerns regarding the existence of antibiotic-resistant Y. pestis strains has prompted efforts to develop safe live vaccines (Titball and Williamson, 2004 ; Feodorova et al, 2007 ; Tidhar et al, 2009 ; Feodorova and Motin, 2012 ; Dentovskaya et al, 2015 ; Derbise et al, 2015 ; Tiner et al, 2016 ; Verma and Tuteja, 2016 ).…”