Mucosal IgA and IFN-γ+ CD8 T cell immunity are important in the efficacy of live Salmonella enteria serovar Choleraesuis vaccines

Zhu, Li; Zhao, Xinxin; Yin, Qianqian; Liu, Xianyong; Chen, Xiang; Huang, Chunjuan; Suo, Xun

doi:10.1038/srep46408

Cited by 14 publications

(8 citation statements)

References 39 publications

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“…Nevertheless, the presence of O-antigen may be essential for the efficacy of inactivated Salmonella vaccines, as the sera induced by inactivated rough strain immunization were not able to kill Salmonella (Rondini et al, 2013 ). Immunization with live Salmonella vaccines elicits robust humoral and T cell-mediated immune responses, both of which are required for preventing Salmonella infection (Wahid et al, 2015 ; Zhu et al, 2017 ). In addition to the protective antigen O-polysaccharide, specific immune responses stimulated by other Salmonella antigens, such as flagellin proteins and OMPs are strongly associated with protection against Salmonella infection (Mastroeni and Menager, 2003 ; Bergman et al, 2005 ).…”

Section: Discussionmentioning

confidence: 99%

Two Novel Salmonella Bivalent Vaccines Confer Dual Protection against Two Salmonella Serovars in Mice

Zhao

Dai

Jia

et al. 2017

Front. Cell. Infect. Microbiol.

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Non-typhoidal Salmonella includes thousands of serovars that are leading causes of foodborne diarrheal illness worldwide. In this study, we constructed three bivalent vaccines for preventing both Salmonella Typhimurium and Salmonella Newport infections by using the aspartate semialdehyde dehydrogenase (Asd)-based balanced-lethal vector-host system. The constructed Asd+ plasmid pCZ11 carrying a subset of the Salmonella Newport O-antigen gene cluster including the wzx-wbaR-wbaL-wbaQ-wzy-wbaW-wbaZ genes was introduced into three Salmonella Typhimurium mutants: SLT19 (Δasd) with a smooth LPS phenotype, SLT20 (Δasd ΔrfbN) with a rough LPS phenotype, and SLT22 (Δasd ΔrfbN ΔpagL::T araC PBAD rfbN) with a smooth LPS phenotype when grown with arabinose. Immunoblotting demonstrated that SLT19 harboring pCZ11 [termed SLT19 (pCZ11)] co-expressed the homologous and heterologous O-antigens; SLT20 (pCZ11) exclusively expressed the heterologous O-antigen; and when arabinose was available, SLT22 (pCZ11) expressed both types of O-antigens, while in the absence of arabinose, SLT22 (pCZ11) expressed only the heterologous O-antigen. Exclusive expression of the heterologous O-antigen in Salmonella Typhimurium decreased the swimming ability of the bacterium and its susceptibility to polymyxin B. Next, the crp gene was deleted from the three recombinant strains for attenuation purposes, generating the three bivalent vaccine strains SLT25 (pCZ11), SLT26 (pCZ11), and SLT27 (pCZ11), respectively. Groups of BALB/c mice (12 mice/group) were orally immunized with 109 CFU of each vaccine strain twice at an interval of 4 weeks. Compared with a mock immunization, immunization with all three vaccine strains induced significant serum IgG responses against both Salmonella Typhimurium and Salmonella Newport LPS. The bacterial loads in the mouse tissues were significantly lower in the three vaccine-strain-immunized groups than in the mock group after either Salmonella Typhimurium or Salmonella Newport lethal challenge. All of the mice in the three vaccine-immunized groups survived the lethal Salmonella Typhimurium challenge. In contrast, SLT26 (pCZ11) and SLT27 (pCZ11) conferred full protection against lethal Salmonella Newport challenge, but SLT25 (pCZ11) provided only 50% heterologous protection. Thus, we developed two novel Salmonella bivalent vaccines, SLT26 (pCZ11) and SLT27 (pCZ11), suggesting that the delivery of a heterologous O-antigen in attenuated Salmonella strains is a prospective approach for developing Salmonella vaccines with broad serovar coverage.

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Section: Discussionmentioning

confidence: 99%

Two Novel Salmonella Bivalent Vaccines Confer Dual Protection against Two Salmonella Serovars in Mice

Zhao

Dai

Jia

et al. 2017

Front. Cell. Infect. Microbiol.

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“…Analysis of RNA transcript levels by qPCR showed that all mutant strains induced less inflammatory cytokine production than the wild-type strain C78-3 at both 6 h (a and c) and 12 h (b and d) post-infection. &, P < 0.05, C78-3 ΔP fur88 TT araC P BAD fur compared to C78-3; #, P < 0.05, ##, P < 0.01, rSC0012(pS-SaoA) compared to rSC0011(pS-SaoA); *, P <0.05, **, P < 0.01, strains with ΔP fur88 TT araC P BAD fur mutation compared to C78-3 stimulate higher heterologous protection than a Δrfc strain without RDAS [26]. Thus, in addition to colonization level, other determining factors may exist to induce the enhanced protection achieved by regulated delayed attenuation.…”

Section: Discussionmentioning

confidence: 99%

Live-attenuated Salmonella enterica serotype Choleraesuis vaccine with regulated delayed fur mutation confer protection against Streptococcus suis in mice

Chen

et al. 2020

BMC Vet Res

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Background: Recombinant Salmonella enterica serotype Choleraesuis (S. Choleraesuis) vaccine vector could be used to deliver heterologous antigens to prevent and control pig diseases. We have previously shown that a liveattenuated S. Choleraesuis vaccine candidate strain rSC0011 (ΔP crp527 ::TT araC P BAD crp Δpmi-2426 ΔrelA199::araC P BAD lacI TT ΔasdA33, Δ, deletion, TT, terminator) delivering SaoA, a conserved surface protein in most of S. suis serotypes, provided excellent protection against S. suis challenge, but occasionally lead to morbidity (enteritidis) in vaccinated mice (approximately 1 in every 10 mice). Thus, alternated attenuation method was sought to reduce the reactogenicity of strain rSC0011. Herein, we described another recombinant attenuated S. Choleraesuis vector, rSC0012 (ΔP fur88 :: TT araC P BAD fur Δpmi-2426 ΔrelA199:: araC P BAD lacI TT ΔasdA33) with regulated delayed fur mutation to avoid inducing disease symptoms while exhibiting a high degree of immunogenicity. Results: The strain rSC0012 strain with the ΔP fur88 ::TT araC P BAD fur mutation induced less production of inflammatory cytokines than strain rSC0011 with the ΔP crp527 ::TT araC P BAD crp mutation in mice. When delivering the same pS-SaoA plasmid, the intraperitoneal LD 50 of rSC0012 was 18.2 times higher than that of rSC0011 in 3-week-old BALB/C mice. rSC0012 with either pS-SaoA or pYA3493 was cleared from spleen and liver tissues 7 days earlier than rSC0011 with same vectors after oral inoculation. The strain rSC0012 synthesizing SaoA induced high titers of anti-SaoA antibodies in both systemic (IgG in serum) and mucosal (IgA in vaginal washes) sites, as well as increased level of IL-4, the facilitator of Th2-type T cell immune response in mice. The recombinant vaccine rSC0012(pS-SaoA) conferred high percentage of protection against S. suis or S. Choleraesuis challenge in BALB/C mice. Conclusions:The live-attenuated Salmonella enterica serotype Choleraesuis vaccine rSC0012(pS-SaoA) with regulated delayed fur mutation provides a foundation for the development of a safe and effective vaccine against S. Choleraesuis and S. suis.

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“…However, there are do exist high levels of colonization but low immunogenicity. A strain with the regulated delayed rfc mutation exhibits superior colonization and yet does not stimulate higher heterologous protection than a Δrfc strain without RDAS [36]. humoral responses than rSC0011 in mice.…”

Section: Discussionmentioning

confidence: 99%

Live-attenuated Salmonella enterica serotype Choleraesuis vaccine with regulated delayed fur mutation confer protection against Streptococcus suis in mice

New

Du³

et al. 2020

Preprint

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Background: Recombinant Salmonella enterica serotype Choleraesuis (S. Choleraesuis) vaccine vector could be used to deliver heterologous antigens to prevent and control pig diseases. We have previously shown that a live-attenuated S. Choleraesuis vaccine candidate strain rSC0011 (ΔPcrp527::TT araC PBAD crp Δpmi-2426 ΔrelA199::araC PBAD lacI TT ΔasdA33, Δ, deletion, TT, terminator) delivering SaoA, a conserved surface protein in most of S. suis serotypes, provided excellent protection against S. suis challenge, but occasionally lead to morbidity (enteritidis) in vaccinated mice (approximately 1 in every 10 mice). Thus, alternated attenuation method was sought to reduce the reactogenicity of strain rSC0011. Herein, we described another recombinant attenuated S. Choleraesuis vector, rSC0012 (ΔPfur88:: TT araC PBAD fur Δpmi-2426 ΔrelA199:: araC PBAD lacI TT ΔasdA33) with regulated delayed fur mutation to avoid inducing disease symptoms while exhibiting a high degree of immunogenicity. Results: The strain rSC0012 strain with the ΔPfur88::TT araC PBAD fur mutation induced less production of inflammatory cytokines than strain rSC0011 with the ΔPcrp527::TT araC PBAD crp mutation in mice. When delivering the same pS-SaoA plasmid, the intraperitoneal LD50 of rSC0012 was 18.2 times higher than that of rSC0011 in 3-week-old BALB/C mice. rSC0012 with either pS-SaoA or pYA3493 was cleared from spleen and liver tissues 7 days earlier than rSC0011 with same vectors after oral inoculation. The strain rSC0012 synthesizing SaoA induced high titers of anti-SaoA antibodies in both systemic (IgG in serum) and mucosal (IgA in vaginal washes) sites, as well as increased level of IL-4, the facilitator of Th2-type T cell immune response in mice. The recombinant vaccine rSC0012(pS-SaoA) conferred high percentage of protection against S. suis or S. Choleraesuis challenge in BALB/C mice.Conclusions: The live-attenuated Salmonella enterica serotype Choleraesuis vaccine rSC0012(pS-SaoA) with regulated delayed fur mutation provides a foundation for the development of a safe and effective vaccine against S. Choleraesuis and S. suis.

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Mucosal IgA and IFN-γ+ CD8 T cell immunity are important in the efficacy of live Salmonella enteria serovar Choleraesuis vaccines

Cited by 14 publications

References 39 publications

Two Novel Salmonella Bivalent Vaccines Confer Dual Protection against Two Salmonella Serovars in Mice

Two Novel Salmonella Bivalent Vaccines Confer Dual Protection against Two Salmonella Serovars in Mice

Live-attenuated Salmonella enterica serotype Choleraesuis vaccine with regulated delayed fur mutation confer protection against Streptococcus suis in mice

Live-attenuated Salmonella enterica serotype Choleraesuis vaccine with regulated delayed fur mutation confer protection against Streptococcus suis in mice

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