A comparison of immunogenicity and protective immunity against experimental plague by intranasal and/or combined with oral immunization of mice with attenuatedSalmonellaserovar Typhimurium expressing secretedYersinia pestisF1 and V antigen

Abstract

We investigated the relative immunogenicity and protective efficacy of recombinant X85MF1 and X85V strains of ΔcyaΔcrpΔasd-attenuated Salmonella Typhimurium expressing, respectively, secreted Yersinia pestis F1 and V antigens, following intranasal (i.n.) or i.n. combined with oral immunization for a mouse model. A single i.n. dose of 10 8 CFU of X85MF1 or X85V induced appreciable serum F1- or V-specific IgG titres, although oral immunization did not. Mice i.n. immunized three times (i.n. × 3) with Salmonella achieved the most substantial F1/V-specific IgG titres, as compared with corresponding titres for an oral-primed, i.n.-boosted (twice; oral-i.n. × 2) immunization regimen. The level of V-specific IgG was significantly greater than that of F1-specific IgG ( P <0.001). Analysis of the IgG antibodies subclasses revealed comparable levels of V-specific Th-2-type IgG1 and Th-1-type IgG2a, and a predominance of F1-specific Th-1-type IgG2a antibodies. In mice immunized intranasally, X85V stimulated a greater IL-10-secreting-cell response in the lungs than did X85MF1, but impaired the induction of gamma-interferon-secreting cells. A program of i.n. × 3 and/or oral-i.n. × 2 immunization with X85V provided levels of protection against a subsequent lethal challenge with Y. pestis , of, respectively, 60% and 20%, whereas 80% protection was provided following the same immunization but with X85MF1.

Evaluation of CD4+/CD8+ T-cell expression and IFN-γ, perforin secretion for B–T constructs of F1 and V antigens of Yersinia pestis

“…Conjugates B1T1, B2T1 of F1 and ai, bf, bi, fd, fi, id and ik of V antigen showed enhanced IFN-γ levels in outbred and inbred strains of mice. The predominance of the IFN-γ response to the different conjugates also indicates that cell mediated immune mechanism may be important in plague infection and these results correlate with similar findings with other studies [56]. During the in vivo protective study four conjugates of V antigen ai, bi, fi and id showed above 90% protection till day 15 and two conjugates of F1 antigen (B1T1 and B2T1) showed in vivo protection during challenge experiments in mice [35,38].…”

Fine-Tuning Synthesis ofYersinia pestisLcrV from Runaway-Like Replication Balanced-Lethal Plasmid in aSalmonella entericaSerovar Typhimurium Vaccine Induces Protection against a LethalY. pestisChallenge in Mice

“…Low levels of anti-LcrV196 IgG were detected in sera obtained from mice immunized with vector control strain 9447(pYA4534) or in preimmune serum. Similar results were observed previously (41). These results indicate that LcrV196 delivered by 9447(pYA4535) induces systemic antibody IgG titers against LcrV196.…”

“…Despite the fact that Liu et al (41) observed that RASV 8501 (hisG ⌬crp-28 ⌬asdA16) delivering full-length flanked Bla SS -LcrV encoded on pYA3495 (AsdA ϩ pBR derivative) to mice immunized by the i.n. route three times (at 2-week intervals between each boost) elicited comparable levels of LcrV-specific IgG1 (Th2) and IgG2a (Th1) and offered 60% protection after intraperitoneal Y. pestis strain Yokohama-R challenge, they observed only 20% protection for mice immunized by a combination of oral priming with two subsequent i.n.…”

“…The induction of IL-10 by LcrV is through the interaction of Toll-like receptor 2 (TLR-2) as well as TLR-6 and cluster of differentiation 14 (CD14) (1,15,58). Immunization with full-length LcrV elicited protective immunity (41), but truncated LcrV forms were also able to elicit an immune response that was protective against a lethal challenge with Y. pestis. These variants included rV10 (lacking amino acid residues 271 to 300) (49), the major protective LcrV region (amino acid residues 135 to 275) (25), LcrV196 (amino acid residues 131 to 326) (5), and a small fragment of LcrV (amino acids 135 to 262) (64).…”

Principles of antidote pharmacology: an update on prophylaxis, post‐exposure treatment recommendations and research initiatives for biological agents

“…Oral immunizations provided >80% protection from 1000 × LD 50 bubonic plague and 100 × LD 50 of pneumonic plague in mice. Hence, this attenuated Salmonella ‐based vaccine has potential as a plague vaccine (Liu et al ., 2007; Yang et al ., 2007).…”