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 Efficacy of a Vaccine Based on Protective Antigen and Killed Spores against Experimental Inhalational Anthrax

2008 ◽  
Vol 77 (3) ◽  
pp. 1197-1207 ◽  
Author(s):  
Yves P. Gauthier ◽  
Jean-Nicolas Tournier ◽  
Jean-Charles Paucod ◽  
Jean-Philippe Corre ◽  
Michèle Mock ◽  
...  
Keyword(s):  
Guinea Pigs ◽  
Protective Immunity ◽  
Protective Antigen ◽  
Virulent Strain ◽  
Neutralizing Antibody ◽  
Cutaneous Anthrax ◽  
Anthrax Vaccines ◽  
Mucosal Secretions ◽  
Highly Virulent ◽  
Lethal Doses

ABSTRACTProtective antigen (PA)-based anthrax vaccines acting on toxins are less effective than live attenuated vaccines, suggesting that additional antigens may contribute to protective immunity. Several reports indicate that capsule or spore-associated antigens may enhance the protection afforded by PA. Addition of formaldehyde-inactivated spores (FIS) to PA (PA-FIS) elicits total protection against cutaneous anthrax. Nevertheless, vaccines that are effective against cutaneous anthrax may not be so against inhalational anthrax. The aim of this work was to optimize immunization with PA-FIS and to assess vaccine efficacy against inhalational anthrax. We assessed the immune response to recombinant anthrax PA fromBacillus anthracis(rPA)-FIS administered by various immunization protocols and the protection provided to mice and guinea pigs infected through the respiratory route with spores of a virulent strain ofB. anthracis. Combined subcutaneous plus intranasal immunization of mice yielded a mucosal immunoglobulin G response to rPA that was more than 20 times higher than that in lung mucosal secretions after subcutaneous vaccination. The titers of toxin-neutralizing antibody and antispore antibody were also significantly higher: nine and eight times higher, respectively. The optimized immunization elicited total protection of mice intranasally infected with the virulentB. anthracisstrain 17JB. Guinea pigs were fully protected, both against an intranasal challenge with 100 50% lethal doses (LD50) and against an aerosol with 75 LD50of spores of the highly virulent strain 9602. Conversely, immunization with PA alone did not elicit protection. These results demonstrate that the association of PA and spores is very much more effective than PA alone against experimental inhalational anthrax.

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 Genetic and Antigenic Diversity of the Surface Protective Antigen Proteins of Erysipelothrix rhusiopathiae

2007 ◽  
Vol 14 (7) ◽  
pp. 813-820 ◽  
Author(s):  
Ho To ◽  
Shinya Nagai
Keyword(s):  
Protective Antigen ◽  
Sequence Similarity ◽  
Immunoblot Analysis ◽  
Amino Acid Sequence Similarity ◽  
Potential Candidate ◽  
Erysipelothrix Rhusiopathiae ◽  
Antigenic Diversity ◽  
Reference Strains ◽  
Spa Types ◽  
Spa Proteins

ABSTRACTThe surface protective antigen (Spa) protein ofErysipelothrix rhusiopathiaehas been shown to be highly immunogenic and is a potential candidate for a new vaccine against erysipelas. In this study, we cloned and sequencedspagenes from allE. rhusiopathiaeserovar reference strains as well as from a serovar 18 strain which was not classified as any species in the genusErysipelothrix.Sequence analysis revealed that the Spa proteins could be classified into three molecular species, including SpaA, which was previously found in serovars 1a and 2, and the newly designated SpaB and SpaC proteins. The SpaA protein is produced byE. rhusiopathiaeserovars 1a, 1b, 2, 5, 8, 9, 12, 15, 16, 17, and N, the SpaB protein is produced byE. rhusiopathiaeserovars 4, 6, 11, 19, and 21, and the SpaC protein is produced only by serovar 18. The amino acid sequence similarity was high among members of each Spa type (96 to 99%) but low between different Spa types (∼60%). The greatest diversity in Spa proteins was found in the N-terminal half of the molecule (50 to 57% similarity), which was shown to be involved in immunoprotection. Coinciding with this, immunoblot analysis revealed that rabbit antisera specific to each Spa reacted strongly with the homologous Spa protein but weakly with heterologous Spa proteins. A mouse cross-protection study showed that the three recombinant Spa (rSpa) proteins elicited complete protection against challenge with homologous strains but that the level of protection against challenge with heterologous strains varied depending on the rSpa protein used for immunization. Our study is the first to demonstrate sequence and antigenic diversity in Spa proteins and to indicate that rSpaC may be the most promising antigen for use as a vaccine component because of its broad cross-protectiveness.

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 Protective Immunity to Anthrax Lethal Toxin with a Nonhuman Primate Adenovirus-Based Vaccine in the Presence of Preexisting Anti-Human Adenovirus Immunity

2005 ◽  
Vol 73 (10) ◽  
pp. 6885-6891 ◽  
Author(s):  
Masahiko Hashimoto ◽  
Julie L. Boyer ◽  
Neil R. Hackett ◽  
James M. Wilson ◽  
Ronald G. Crystal
Keyword(s):  
Nonhuman Primate ◽  
Neutralizing Antibodies ◽  
Protective Immunity ◽  
Protective Antigen ◽  
Recombinant Adenovirus ◽  
Lethal Toxin ◽  
Effective Vaccine ◽  
Anthrax Lethal Toxin ◽  
Adenovirus Vaccine

ABSTRACT Prevention or therapy for bioterrorism-associated anthrax infections requires rapidly acting effective vaccines. We recently demonstrated (Y. Tan, N. R. Hackett, J. L. Boyer, and R. G. Crystal, Hum. Gene Ther. 14:1673-1682, 2003) that a single administration of a recombinant serotype 5 adenovirus (Ad) vector expressing anthrax protective antigen (PA) provides rapid protection against anthrax lethal toxin challenge. However, approximately 35 to 50% of humans have preexisting neutralizing antibodies against Ad5. This study assesses the hypothesis that a recombinant adenovirus vaccine based on the nonhuman primate-derived serotype AdC7, against which humans do not have immunity, expressing PA (AdC7PA) will protect against anthrax lethal toxin even in the presence of preexisting anti-Ad5 immunity. Naive and Ad5-immunized BALB/c mice received (intramuscularly) 108 to 1011 particle units (PU) of AdC7PA, Ad5PA (a human serotype Ad5-based vector expressing a secreted form of PA), or AdNull (an Ad5 vector with no transgene). Robust anti-PA immunoglobulin G and neutralizing antibodies were detected by 2 to 4 weeks following administration of AdC7PA to naive or Ad5 preimmunized mice, whereas low anti-PA titers were detected in Ad5-preimmunized mice following administration of Ad5PA. To assess protection in vivo, naive or mice previously immunized against Ad5 were immunized with AdC7PA or Ad5PA and then challenged with a lethal intravenous dose of Bacillus anthracis lethal toxin. Whereas Ad5PA protected naive mice against challenge with B. anthracis lethal toxin, Ad5PA was ineffective in mice that were previously immunized against Ad5. In contrast, AdC7PA functioned effectively not only to protect naive mice but also to protect Ad5-preimmunized mice, with 100% survival after lethal toxin challenge. These data suggest the nonhuman-based vector AdC7PA is an effective vaccine for the development of protective immunity against B. anthracis and importantly functions as a “sero-switch” base for an adenovirus vaccine to function in the context of preexisting anti-Ad immunity.

scholarly journals Encapsulation of Recombinant MOMP in Extended-Releasing PLGA 85:15 Nanoparticles Confer Protective Immunity Against a Chlamydia muridarum Genital Challenge and Re-Challenge

2021 ◽  
Vol 12 ◽  
Author(s):  
Rajnish Sahu ◽  
Saurabh Dixit ◽  
Richa Verma ◽  
Skyla A. Duncan ◽  
Lula Smith ◽  
...  
Keyword(s):  
T Cells ◽  
Protective Immunity ◽  
Protective Efficacy ◽  
Immune Effector ◽  
Chlamydia Muridarum ◽  
Humoral Immune ◽  
Iga Antibodies ◽  
Ifn Γ ◽  
First Time

Recently we reported the immune-potentiating capacity of a Chlamydia nanovaccine (PLGA-rMOMP) comprising rMOMP (recombinant major outer membrane protein) encapsulated in extended-releasing PLGA [poly (D, L-lactide-co-glycolide) (85:15)] nanoparticles. Here we hypothesized that PLGA-rMOMP would bolster immune-effector mechanisms to confer protective efficacy in mice against a Chlamydia muridarum genital challenge and re-challenge. Female BALB/c mice received three immunizations, either subcutaneously (SC) or intranasally (IN), before receiving an intravaginal challenge with C. muridarum on day 49 and a re-challenge on day 170. Both the SC and IN immunization routes protected mice against genital challenge with enhanced protection after a re-challenge, especially in the SC mice. The nanovaccine induced robust antigen-specific Th1 (IFN-γ, IL-2) and IL-17 cytokines plus CD4+ proliferating T-cells and memory (CD44high CD62Lhigh) and effector (CD44high CD62Llow) phenotypes in immunized mice. Parallel induction of antigen-specific systemic and mucosal Th1 (IgG2a, IgG2b), Th2 (IgG1), and IgA antibodies were also noted. Importantly, immunized mice produced highly functional Th1 avidity and serum antibodies that neutralized C. muridarum infectivity of McCoy fibroblasts in-vitro that correlated with their respective protection levels. The SC, rather than the IN immunization route, triggered higher cellular and humoral immune effectors that improved mice protection against genital C. muridarum. We report for the first time that the extended-releasing PLGA 85:15 encapsulated rMOMP nanovaccine confers protective immunity in mice against genital Chlamydia and advances the potential towards acquiring a nano-based Chlamydia vaccine.

Changes in alcohol history taking by psychiatric junior doctors: an audit

1995 ◽  
Vol 12 (1) ◽  
pp. 37-39 ◽  
Author(s):  
Simon J Taylor
Keyword(s):  
Illicit Drug ◽  
Statistical Significance ◽  
Inpatient Admission ◽  
Junior Doctors ◽  
History Taking ◽  
Drug Usage ◽  
Acute Psychiatric Wards ◽  
First Time

AbstractObjective: In recent years a number of articles have highlighted deficiencies in drinking histories taken by junior doctors. This study examines whether standards have improved as a result. It also examines for the first time: 1. the quality of drinking histories taken from patients following parasuicide; and 2. the quality of illicit drug usage histories.Method: An audit of case notes was undertaken of 114 patients admitted to a district hospital's acute psychiatric wards or assessed following overdose. Two periods were considered; one preceding many of the articles, and the second four years later.Results: There was an overall improvement from 58% of histories in 1988 having no mention of alcohol usage to 25% in 1992. (X2MH=10.57, p<0.01). There was, however, insufficient improvement of quantitative histories to reach statistical significance. Histories taken as part of an overdose assessment were not significantly different from those taken for inpatient admission. In 1992, 27% of patients had any illicit drug usage history recorded which represented a statistically significant improvement (X2MH=5.91, p<0.02) compared with four years earlier.Conclusions: Although improvements have been noted, alcohol and drug histories remain inadequate.

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.

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