<p>Animal model studies used to predict vaccine efficacy in humans present a considerable challenge, as direct extrapolation of experimental results to humans is impermissible for a number of reasons. One of the primary causes of differing responses to vaccination between humans and rodents lies in interspecies differences in pathogen recognition receptors. Additionally, there are species-specific repertoires of B and T cells, as well as HLA-mediated presentation of dominant epitopes to CD4 and CD8 T cells. Due to these limitations, candidate vaccines are tested in several species of both small and large animals, which is expected to yield data that are more applicable to humans. Objective of the study was a comparative assessment of the protective efficacy of the 231Δ<i>nlpD</i> and EVΔ<i>lpxM</i> strains of the plague bacterium, which differed in antigenic composition, in two species of laboratory animals following a single subcutaneous administration, either separately or in combination. The protective efficacy of the tested strains was evaluated by calculating the immunity index following subcutaneous challenge in mice and guinea pigs. As in previous experiments [1], administration of monocomponent vaccines based on attenuated <i>Yersinia pestis</i> strains 231Δ<i>nlpD</i> or EVΔ<i>lpxM</i> selectively induced protection in only mice or only guinea pigs, respectively. Immunization with a mixture of the attenuated strains yielded an immunity index greater than 10⁸ in both species of laboratory animals. Combined subcutaneous immunization of mice and guinea pigs with the attenuated <i>Y. pestis</i> strains 231Δ<i>nlpD</i> and EVΔ<i>lpxM</i> enhanced the intensity of immunity against plague upon subcutaneous challenge with the wild-type strain 231.</p>