Oral immunization of Escherichia albertii strain DM104 induces protective immunity against Shigella dysenteriae type 4 in mouse model

2021 ◽  
Author(s):  
Fatema Moni Chowdhury ◽  
Chowdhury Rafiqul Ahsan ◽  
Nils-Kåre Birkeland
Keyword(s):  
Protective Immunity ◽  
Protective Efficacy ◽  
High Titer ◽  
Lethal Dose ◽  
Oral Immunization ◽  
Shigella Dysenteriae ◽  
Effective Vaccine ◽  
Mice Model ◽  
Environmental Strain ◽  
Whole Cell Lysate

AbstractThe recent rise of antibiotic resistance and lack of an effective vaccine make the scenario of shigellosis alarming in developing countries like Bangladesh. In recent years, our group reported the vaccine efficacy of a non-pathogenic Escherichia albertii strain DM104 in different animal models, where an ocularly administered vaccine in the guinea pig eye model against Shigella dysenteriae type 4 challenge showed high protective efficacy and also induced a high titer of serum IgG against S. dysenteriae type 4 whole cell lysate (WCL) and LPS. In this study, we report further evaluation of the non-invasive and non-toxic environmental strain DM104 as a vaccine candidate against S. dysenteriae type 4 in mice model. Oral immunization of live DM104 bacterial strain demonstrated better protective immunity in mice model by showing 90% protection in mice against live S. dysenteriae type 4 lethal dose challenge and by inducing effective humoral and mucosal immune responses.

scholarly journals Oral Immunization with a Salmonella typhimurium Vaccine Vector Expressing Recombinant Enterotoxigenic Escherichia coli K99 Fimbriae Elicits Elevated Antibody Titers for Protective Immunity

1998 ◽  
Vol 66 (11) ◽  
pp. 5470-5476 ◽  
Author(s):  
Miguel A. Ascón ◽  
David M. Hone ◽  
Nancy Walters ◽  
David W. Pascual
Keyword(s):  
Escherichia Coli ◽  
Salmonella Typhimurium ◽  
Protective Immunity ◽  
Mononuclear Cells ◽  
Immunoglobulin A ◽  
Oral Immunization ◽  
Enterotoxigenic Escherichia Coli ◽  
Effective Vaccine ◽  
Antibody Titers ◽  
And Control

ABSTRACT Bovine enterotoxigenic Escherichia coli (ETEC) continues to cause mortality in piglets and newborn calves. In an effort to develop a safe and effective vaccine for the prevention of F5+ ETEC infections, a balanced lethalasd + plasmid carrying the complete K99 operon was constructed and designated pMAK99-asd +. Introduction of this plasmid into an attenuated Salmonella typhimurium Δaro Δasd strain, H683, resulted in strain AP112, which stably expresses E. coli K99 fimbriae. A single oral immunization of BALB/c and CD-1 mice with strain AP112 elicited significant mucosal immunoglobulin A (IgA) titers that remained elevated for >11 weeks. IgA and IgG responses in serum specific for K99 fimbriae were also induced, with a prominent IgG1, as well as IgG2a and IgG2b, titer. To assess the derivation of these antibodies, a K99 isotype-specific B-cell ELISPOT analysis was conducted by using mononuclear cells from the lamina propria of the small intestines (LP), Peyer’s patches (PP), and spleens of vaccinated and control BALB/c mice. This analysis revealed elevated numbers of K99 fimbria-specific IgA-producing cells in the LP, PP, and spleen, whereas elevated K99 fimbria-specific IgG-producing cells were detected only in the PP and spleen. These antibodies were important for protective immunity. One-day-old neonates from dams orally immunized with AP112 were provided passive protection against oral challenge with wild-type ETEC, in contrast to challenged neonates from unvaccinated dams or from dams vaccinated with a control Salmonella vector. These results confirm that oral Salmonella vaccine vectors effectively deliver K99 fimbriae to mucosal inductive sites for sustained elevation of IgA and IgG antibodies and for eliciting protective immunity.

scholarly journals IgY antibodies against Ebola virus possess post-exposure protection in a murine pseudovirus challenge model and excellent thermostability

2021 ◽  
Vol 15 (3) ◽  
pp. e0008403
Author(s):  
Yuan Zhang ◽  
Yanqiu Wei ◽  
Yunlong Li ◽  
Xuan Wang ◽  
Yang Liu ◽  
...  
Keyword(s):  
Thermal Stability ◽  
Ebola Virus ◽  
Protective Efficacy ◽  
High Titer ◽  
Lethal Dose ◽  
Hemorrhagic Fever ◽  
High Dose ◽  
Excellent Thermal Stability ◽  
Post Exposure

Ebola virus (EBOV) is one of the most virulent pathogens that causes hemorrhagic fever and displays high mortality rates and low prognosis rates in both humans and nonhuman primates. The post-exposure antibody therapies to prevent EBOV infection are considered effective as of yet. However, owing to the poor thermal stability of mammalian antibodies, their application in the tropics has remained limited. Therefore, a thermostable therapeutic antibody against EBOV was developed modelled on the poultry(chicken) immunoglobulin Y (IgY). The IgY antibodies retaining their neutralising activity at 25°C for one year, displayed excellent thermal stability, opposed to conventional polyclonal antibodies (pAbs) or monoclonal antibodies (mAbs). Laying hens were immunised with a variety of EBOV vaccine candidates and it was confirmed that VSVΔG/EBOVGP encoding the EBOV glycoprotein could induce high titer neutralising antibodies against EBOV. The therapeutic efficacy of immune IgY antibodies in vivo was evaluated in the newborn Balb/c mice who have been challenged with the VSVΔG/EBOVGP model. Mice that have been challenged with a lethal dose of the pseudovirus were treated 2 or 24 h post-infection with different doses of anti-EBOV IgY. The group receiving a high dose of 106 NAU/kg (neutralising antibody units/kilogram) showed complete protection with no symptoms of a disease, while the low-dose group was only partially protected. Conversely, all mice receiving naive IgY died within 10 days. In conclusion, the anti-EBOV IgY exhibits excellent thermostability and protective efficacy. Anti-EBOV IgY shows a lot of promise in entering the realm of efficient Ebola virus treatment regimens.

scholarly journals Immunization with Truncated Recombinant Protein SpaC of Erysipelothrix rhusiopathiae Strain 715 Serovar 18 Confers Protective Immunity against Challenge with Various Serovars

2010 ◽  
Vol 17 (12) ◽  
pp. 1991-1997 ◽  
Author(s):  
Ho To ◽  
Shuichi Someno ◽  
Shinya Nagai ◽  
Tomohiro Koyama ◽  
Tetsuji Nagano
Keyword(s):  
Protective Immunity ◽  
Protective Antigen ◽  
Protective Efficacy ◽  
Statistical Significance ◽  
Effective Vaccine ◽  
Erysipelothrix Rhusiopathiae ◽  
Helical Domain ◽  
First Time ◽  
Highly Virulent ◽  
Spa Proteins

ABSTRACTPreviously, we showed that surface protective antigen (Spa) proteins ofErysipelothrix rhusiopathiaecan be classified into three molecular species—SpaA, SpaB, and SpaC—and that SpaC is the most broadly cross-protective antigen among the three Spa proteins. In this study, we examined the ability of the α-helical domain, which comprises the N-terminal half of SpaC, to elicit cross-protective immunity in mice and pigs. Mice actively immunized with the full-length protein (rSpaC664) or the α-helical domain (rSpaC427), but not the C-terminal domain (rSpaC253), were protected against challenge withE. rhusiopathiaeserovars 1a, 2, 6, 19, and 18 expressing heterologous (SpaA or SpaB) and homologous (SpaC) Spas. The α-helical domain seemed to provide better protection than rSpaC664, although the differences did not reach statistical significance. Similarly, mice passively immunized with rabbit anti-rSpaC664 or anti-rSpaC427 sera, but not anti-rSpaC253 serum, were protected from challenge with various serovars. Pigs immunized with SpaC427 also developed specific antibodies against Spa proteins and were protected from challenge with the highly virulent heterologousE. rhusiopathiaestrain Fujisawa (serovar 1a). Taken together, these results demonstrate for the first time the striking protective efficacy of the α-helical domain-mediated immunization in both mice and pigs, thereby highlighting its utility as the most promising candidate for the development of a safe and effective vaccine against erysipelas.

scholarly journals Evaluation of Safety and Protective Efficacy of a waaJ and spiC Double Deletion Korean Epidemic Strain of Salmonella enterica Serovar Gallinarum

2021 ◽  
Vol 8 ◽  
Author(s):  
Jun-Feng Zhang ◽  
Ke Shang ◽  
Bai Wei ◽  
Yea-Jin Lee ◽  
Jong-Yeol Park ◽  
...  
Keyword(s):  
Vaccine Candidate ◽  
Protective Efficacy ◽  
Virulence Gene ◽  
Oral Immunization ◽  
The Body ◽  
Deletion Strain ◽  
Effective Vaccine ◽  
Epidemic Strain ◽  
Double Deletion

With an aim to develop a highly attenuated and strongly immunogenic distinguishable vaccine candidate, a waaJ (a gene involved in the synthesis of lipopolysaccharide) and spiC (a virulence gene) double deletion Korean epidemic strain of S. enterica ser. Gallinarum (SG005) was constructed. Our results showed that the growth and biochemical characteristics were not altered by this double deletion. The double deletion strain contained dual markers. One was a bacteriological marker (rough phenotype) and the other was a serological marker helping distinguish infected chickens from vaccinated chickens. The double deletion strain showed good genetic stability and reduced resistance to environmental stresses in vitro; furthermore, it was extremely safe and highly avirulent in broilers. Single intramuscular or oral immunization of 7-day-old broilers with the double deletion strain could stimulate the body to produce antibody levels similar to the conventional vaccine strain SG9R. In addition, against a lethal wild-type challenge, it conferred effective protection that was comparable to that seen in the group vaccinated with SG9R. In conclusion, this double deletion strain may be an effective vaccine candidate for controlling S. enterica ser. Gallinarum infection in broilers.

scholarly journals Mucosal Administration of Recombinant Baculovirus Displaying Toxoplasma gondii ROP4 Confers Protection Against T. gondii Challenge Infection in Mice

2021 ◽  
Vol 11 ◽  
Author(s):  
Keon-Woong Yoon ◽  
Ki-Back Chu ◽  
Hae-Ji Kang ◽  
Min-Ju Kim ◽  
Gi-Deok Eom ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Protective Efficacy ◽  
Lethal Dose ◽  
Recombinant Baculovirus ◽  
Oral Immunization ◽  
Challenge Infection ◽  
Antibody Responses ◽  
Physical Contact ◽  
Lethal Challenge ◽  
Iga Antibody

Pathogens require physical contact with the mucosal surface of the host organism to initiate infection and as such, vaccines eliciting both mucosal and systemic immune responses would be promising. Studies involving the use of recombinant baculoviruses (rBVs) as mucosal vaccines are severely lacking despite their inherently safe nature, especially against pathogens of global importance such as Toxoplasma gondii. Here, we generated rBVs displaying T. gondii rhoptry protein 4 (ROP4) and evaluated their protective efficacy in BALB/c mice following immunization via intranasal (IN) and oral routes. IN immunization with the ROP4-expressing rBVs elicited higher levels of parasite-specific IgA antibody responses compared to oral immunization. Upon challenge infection with a lethal dose of T. gondii ME49, IN immunization elicited significantly higher parasite-specific antibody responses in the mucosal tissues such as intestines, feces, vaginal samples, and brain than oral immunization. Marked increases in IgG and IgA antibody-secreting cell (ASC) responses were observed from intranasally immunized mice. IN immunization elicited significantly enhanced induction of CD4+, CD8+ T cells, and germinal center B (GC B) cell responses from secondary lymphoid organs while limiting the production of the inflammatory cytokines IFN-γ and IL-6 in the brain, all of which contributed to protecting mice against T. gondii lethal challenge infection. Our findings suggest that IN delivery of ROP4 rBVs induced better mucosal and systemic immunity against the lethal T. gondii challenge infection compared to oral immunization.

scholarly journals Comparison of Immunogenicity and Protective Efficacy of the Intranasal and Intraperitoneal Immunization Routes of Escherichia albertii Strain DM104 in Mouse Model

2020 ◽  
Vol 37 (2) ◽  
pp. 38-41
Author(s):  
Fatema Moni Chowdhury ◽  
Nils Kare Birkeland ◽  
Chowdhury Rafiqul Ahsan
Keyword(s):  
Mouse Model ◽  
Vaccine Strain ◽  
Protective Efficacy ◽  
High Titre ◽  
Shigella Dysenteriae ◽  
Control Group ◽  
Intranasal Route ◽  
Intranasal Immunization ◽  
Eye Model ◽  
Whole Cell Lysate

In recent years, our group isolated the Escherichia albertii strain DM104 and characterized it as a vaccine strain against Shigella dysenteriae type 4 in the guinea pig eye model. Protective efficacy of different routes of immunization such as intranasal, oral, and intrarectal routes were also determined and compared by challenging immunized guinea pigs against live S. dysenteriae. In the current study, we compared the intranasal and intraperitoneal routes of immunizations with the DM104 vaccine strain in mice to understand the better route of administration of the DM104 vaccine and its immunogenicity as well as protective efficacy in mouse model. The results indicate that the immune response elicited by the DM104 strain is strongly dependent on the immunization route, with the intranasal route being more effective than the intraperitoneal route following intraperitoneal live S. dysenteriae challenge. Intranasal immunization yielded 80% protective efficacy in immunized mice whereas, intraperitoneal immunization could not provide any protection. Protection generated by intranasal immunization was accompanied by high titre of anti-whole cell lysate IgG and IgA in DM104 immunized sera compared to sera collected from mice of control group. All these data demonstrate the intranasal route of the vaccine DM104 strain in mouse model to be a better immunization route to protect the animals against live S. dysenteriae challenge. Bangladesh J Microbiol, Volume 37 Number 2 December 2020, pp 38-41

scholarly journals Virus-Like Particle Vaccine Induces Protective Immunity against Homologous and Heterologous Strains of Influenza Virus

2007 ◽  
Vol 81 (7) ◽  
pp. 3514-3524 ◽  
Author(s):  
Fu-Shi Quan ◽  
Chunzi Huang ◽  
Richard W. Compans ◽  
Sang-Moo Kang
Keyword(s):  
Influenza Virus ◽  
Immune Responses ◽  
Protective Immunity ◽  
Protective Efficacy ◽  
High Serum ◽  
Influenza Viruses ◽  
Effective Vaccine ◽  
Lethal Challenge ◽  
Virus Challenge ◽  
Vaccine Approach

ABSTRACT Recurrent outbreaks of highly pathogenic avian influenza virus pose the threat of pandemic spread of lethal disease and make it a priority to develop safe and effective vaccines. Influenza virus-like particles (VLPs) have been suggested to be a promising vaccine approach. However, VLP-induced immune responses, and their roles in inducing memory immune responses and cross-protective immunity have not been investigated. In this study, we developed VLPs containing influenza virus A/PR8/34 (H1N1) hemagglutinin (HA) and matrix (M1) proteins and investigated their immunogenicity, long-term cross-protective efficacy, and effects on lung proinflammatory cytokines in mice. Intranasal immunization with VLPs containing HA induced high serum and mucosal antibody titers and neutralizing activity against PR8 and A/WSN/33 (H1N1) viruses. Mice immunized with VLPs containing HA showed little or no proinflammatory lung cytokines and were protected from a lethal challenge with mouse-adapted PR8 or WSN viruses even 5 months postimmunization. Influenza VLPs induced mucosal immunoglobulin G and cellular immune responses, which were reactivated rapidly upon virus challenge. Long-lived antibody-secreting cells were detected in the bone marrow of immunized mice. Immune sera administered intranasally were able to confer 100% protection from a lethal challenge with PR8 or WSN, which provides further evidence that anti-HA antibodies are primarily responsible for preventing infection. Taken together, these results indicate that nonreplicating influenza VLPs represent a promising strategy for the development of a safe and effective vaccine to control the spread of lethal influenza viruses.

scholarly journals Induction of Immune Responses in Mice after Oral Immunization with Recombinant Lactobacillus casei Strains Expressing Enterotoxigenic Escherichia coli F41 Fimbrial Protein

2009 ◽  
Vol 75 (13) ◽  
pp. 4491-4497 ◽  
Author(s):  
Jian-Kui Liu ◽  
Xi-Lin Hou ◽  
Chun-Hua Wei ◽  
Li-Yun Yu ◽  
Xiao-Jie He ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Lactobacillus Casei ◽  
Vaccine Development ◽  
Lethal Dose ◽  
Oral Immunization ◽  
Enterotoxigenic Escherichia Coli ◽  
Interleukin 4 ◽  
Effective Vaccine ◽  
Standard Type ◽  
Fimbrial Protein

ABSTRACT In an effort to develop a safe and effective vaccine for the prevention of enterotoxigenic Escherichia coli (ETEC) F41 infections, we have developed a surface antigen display system using poly-γ-glutamate synthetase A (PgsA) as an anchoring matrix. The recombinant fusion proteins comprised of PgsA and fimbrial protein of F41 were stably expressed in Lactobacillus casei 525. Surface localization of the fusion protein was verified by immunoblotting, immunofluorescence microscopy, and flow cytometry. Oral inoculation of recombinant L. casei 525 into specific-pathogen-free BALB/c mice resulted in significant mucosal immunoglobulin A (IgA) titers that remained elevated for >16 weeks. High levels of IgG responses in sera specific for F41 fimbriae were also induced, with prominent IgG1 titers as well as IgG2a and IgG2b titers. The helper T-cell (Th) response was Th2-cell dominant, as evidenced by increased mucosal and systemic interleukin-4-producing T cells and a concomitant elevation of serum IgG1 antibody responses. More than 80% of the mice were protected against challenge with a 2 × 104-fold 50% lethal dose of standard-type F41 (C83919). The induced antibodies were important for eliciting a protective immune response against F41 infection. These results indicated that the use of recombinant L. casei 525 could be a valuable strategy for future vaccine development for ETEC.

scholarly journals Vaccination with DNA Encoding the Immunodominant LACK Parasite Antigen Confers Protective Immunity to Mice Infected with Leishmania major

1997 ◽  
Vol 186 (7) ◽  
pp. 1137-1147 ◽  
Author(s):  
Sanjay Gurunathan ◽  
David L. Sacks ◽  
Daniel R. Brown ◽  
Steven L. Reiner ◽  
Hughes Charest ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Protective Immunity ◽  
Leishmania Major ◽  
Protective Efficacy ◽  
Dna Vaccination ◽  
Attractive Alternative ◽  
Dna Immunization ◽  
Dna Encoding ◽  
Ifn Γ

To determine whether DNA immunization could elicit protective immunity to Leishmania major in susceptible BALB/c mice, cDNA for the cloned Leishmania antigen LACK was inserted into a euykaryotic expression vector downstream to the cytomegalovirus promoter. Susceptible BALB/c mice were then vaccinated subcutaneously with LACK DNA and challenged with L. major promastigotes. We compared the protective efficacy of LACK DNA vaccination with that of recombinant LACK protein in the presence or absence of recombinant interleukin (rIL)-12 protein. Protection induced by LACK DNA was similar to that achieved by LACK protein and rIL-12, but superior to LACK protein without rIL-12. The immunity conferred by LACK DNA was durable insofar as mice challenged 5 wk after vaccination were still protected, and the infection was controlled for at least 20 wk after challenge. In addition, the ability of mice to control infection at sites distant to the site of vaccination suggests that systemic protection was achieved by LACK DNA vaccination. The control of disease progression and parasitic burden in mice vaccinated with LACK DNA was associated with enhancement of antigen-specific interferon-γ (IFN-γ) production. Moreover, both the enhancement of IFN-γ production and the protective immune response induced by LACK DNA vaccination was IL-12 dependent. Unexpectedly, depletion of CD8+ T cells at the time of vaccination or infection also abolished the protective response induced by LACK DNA vaccination, suggesting a role for CD8+ T cells in DNA vaccine induced protection to L. major. Thus, DNA immunization may offer an attractive alternative vaccination strategy against intracellular pathogens, as compared with conventional vaccination with antigens combined with adjuvants.

scholarly journals Inhibition of the oxygen sensor PHD2 in the liver improves survival in lactic acidosis by activating the Cori cycle

2015 ◽  
Vol 112 (37) ◽  
pp. 11642-11647 ◽  
Author(s):  
Tomohiro Suhara ◽  
Takako Hishiki ◽  
Masataka Kasahara ◽  
Noriyo Hayakawa ◽  
Tomoko Oyaizu ◽  
...  
Keyword(s):  
Lactic Acidosis ◽  
Oxygen Sensor ◽  
Lethal Dose ◽  
Hypoxia Inducible Factor ◽  
Tolerance Test ◽  
Null Mouse ◽  
Mice Model ◽  
Hypoxic Response ◽  
Cori Cycle

Loss of prolyl hydroxylase 2 (PHD2) activates the hypoxia-inducible factor-dependent hypoxic response, including anaerobic glycolysis, which causes large amounts of lactate to be released from cells into the circulation. We found that Phd2-null mouse embryonic fibroblasts (MEFs) produced more lactate than wild-type MEFs, as expected, whereas systemic inactivation of PHD2 in mice did not cause hyperlacticacidemia. This unexpected observation led us to hypothesize that the hypoxic response activated in the liver enhances the Cori cycle, a lactate–glucose carbon recycling system between muscle and liver, and thereby decreases circulating lactate. Consistent with this hypothesis, blood lactate levels measured after a treadmill or lactate tolerance test were significantly lower in Phd2-liver-specific knockout (Phd2-LKO) mice than in control mice. An in vivo 13C-labeled lactate incorporation assay revealed that the livers of Phd2-LKO mice produce significantly more glucose derived from 13C-labeled lactate than control mice, suggesting that blockade of PHD2 in the liver ameliorates lactic acidosis by activating gluconeogenesis from lactate. Phd2-LKO mice were resistant to lactic acidosis induced by injection of a lethal dose of lactate, displaying a significant elongation of survival. Moreover, oral administration of a PHD inhibitor improved survival in an endotoxin shock mice model. These data suggest that PHD2 is a potentially novel drug target for the treatment of lactic acidosis, which is a serious and often fatal complication observed in some critically ill patients.

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