Comparison of Immunological Responses of Plague Vaccines F1 + rV270 and EV76 in Chinese-Origin Rhesus Macaque, Macaca mulatta

Abstract

The subunit vaccine SV1 (20 μg F1 + 10 μg rV270) has been identified as the optimal formulation in mice, which provided a good protection against plague in mice, guinea pigs and rabbits. To compare SV1 and SV2 (200 μg F1 + 100 μg rV270) with live attenuated vaccine EV76, antibody responses, protective efficacy, cytokines (IFN‐γ, TNF‐α, IL‐2, IL‐4, IL‐10 and IL‐12) production, CD4/CD8 ratio and CD69+ T‐cell activation marker were determined in sera of the immunized Chinese‐origin rhesus macaques, Macaca mulatta. The immunized animals with SV1 or SV2 developed higher anti‐rV270 IgG titre, while those immunized with EV76 elicited a negligible IgG to V antigen, indicating that subunit vaccine (SV) had an advantage over EV76 in terms of the indispensable role of anti‐V antibody against Yersinia pestis. There was no significant antibody titre difference between SV1 and SV2, suggesting that the immune response may have been saturated at the dose level of SV1. There were no statistical changes for CD4/CD8 ratios, IL‐4 and CD69 levels between the three‐vaccine immunized groups. However, a significant higher level of IL‐12 was observed in the EV76 immunized animals, indicating that EV76 had an advantage over SV in respect of cellular immunity. Complete protection was observed for the immunized animals with SV and EV76, revealing that SV has a similar protective efficacy with EV76 against 6 × 106 CFU of Y. pestis challenge by subcutaneous route in Chinese‐origin rhesus macaques.

LcrV Delivered via Type III Secretion System of Live Attenuated Yersinia pseudotuberculosis Enhances Immunogenicity against Pneumonic Plague

“…Virulence of 10055 determined by oral administration in Swiss Webster mice demonstrated that the LD 50 of 10055 increased at least by 10 2 -fold (Ͼ4 ϫ 10 9 CFU) compared to that of the wild-type strain (LD 50 ϭ 5 ϫ 10 7 CFU). But we did not observe any changes in the virulence of 10052 (⌬msbB868) and 10053 [⌬msbB868::P msbB ::msbB (EC) ] (data not shown).…”

“…Actual numbers of CFU inoculated were determined by plating serial dilutions onto LB agar. The experiment was repeated one time, and data were combined to calculate the LD 50 .…”

“…Mice were acclimated for 1 week after arrival and deprived of food and water for 6 h before starting experiments. The median lethal dose (LD 50 ) of the Y. pseudotuberculosis strains in mice was determined according to previous procedures with certain modifications (73)(74)(75). Overnight cultures of bacteria were grown at 26°C in LB supplemented with 0.05% arabinose when needed.…”

“…Studies demonstrated that Chinese-origin rhesus macaques immunized with EV76 or mice immunized with the Y. pestis ⌬smpB-ssrA mutant primed a higher anti-F1 IgG titer but an almost undetectable titer with respect to LcrV antigen (38,50), results that are consistent with other studies of animals immunized with the EV76 or KWC vaccine (51)(52)(53)(54)(55)(56)(57). Mice vaccinated with Y. pestis KIM5 (lacking pgm) generated the CD4 and CD8 T cells that synergistically conferred protection against plague, but T cells from those vaccinated mice could not recognize LcrV (47).…”

IL-17A Produced by Neutrophils Protects against Pneumonic Plague through Orchestrating IFN-γ–Activated Macrophage Programming

“…(25), which is considered avirulent in humans but highly lethal in mice (26). Strain 141 was isolated from Marmota himalayana in the Qinghai-Tibet plateau and is highly virulent to both humans and Rhesus macaques (27)(28)(29). Y. pestis bacilli were grown overnight at 26˚C with continuous shaking in Bacto heart infusion broth.…”