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Immunization with an autotransporter protein of Orientia tsutsugamushi provides protective immunity against scrub typhus.

Ha NY, Sharma P, Kim G, Kim Y, Min CK, Choi MS, Kim IS, Cho NH - PLoS Negl Trop Dis (2015)

Bottom Line: Despite the wide range of preventative approaches that have been attempted in the past 70 years, all have failed to develop an effective prophylactic vaccine.Currently, the selection of the proper antigens is one of the critical barriers to generating cross-protective immunity against antigenically-variable strains of O. tsutsugamushi.Our findings demonstrate that ScaA functions as a bacterial adhesion factor, and anti-ScaA antibody significantly neutralizes bacterial infection of host cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.

ABSTRACT

Background: Scrub typhus is an acute febrile disease caused by Orientia tsutsugamushi infection. Recently, the rapid increase of scrub typhus incidence in several countries within the endemic region has become a serious public health issue. Despite the wide range of preventative approaches that have been attempted in the past 70 years, all have failed to develop an effective prophylactic vaccine. Currently, the selection of the proper antigens is one of the critical barriers to generating cross-protective immunity against antigenically-variable strains of O. tsutsugamushi.

Methodology/principal findings: We examined the potential role of ScaA protein, an autotransporter protein of O. tsutsugamushi, in bacterial pathogenesis and evaluated the protective attributes of ScaA immunization in lethal O. tsutsugamushi infection in mice. Our findings demonstrate that ScaA functions as a bacterial adhesion factor, and anti-ScaA antibody significantly neutralizes bacterial infection of host cells. In addition, immunization with ScaA not only provides protective immunity against lethal challenges with the homologous strain, but also confers significant protection against heterologous strains when combined with TSA56, a major outer membrane protein of O. tsutsugamushi.

Conclusions/significance: Immunization of ScaA proteins provides protective immunity in mice when challenged with the homologous strain and significantly enhanced protective immunity against infection with heterologous strains. To our knowledge, this is the most promising result of scrub typhus vaccination trials against infection of heterologous strains in mouse models thus far.

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Related in: MedlinePlus

Protective role of anti-ScaA immunity.(A) Anti-ScaA antibody inhibited O. tsutsugamushi infection into host cells. HeLa cells were infected with the pathogen in the presence of the indicated anti-Sca antibodies or nonimmune serum. At 4 h after infection, bacterial infection was examined using confocal microscopy after differential immunoflourescent staining (see materials and methods). (B) The O. tsutsugamushi per host cell ratio was determined from three independent experiments in (A). **, p < 0.01. (C) Survival curves of immunized mice following lethal challenge with O. tsutsugamushi. Mice (n = 5/group) were immunized with the indicated antigen from the Boryong strain and challenged intraperitoneally with 100 x LD50 of O. tsutsugamushi Boryong strain. Their survival was monitored until all the surviving mice recovered from the disease. This graph is a representative survival curve of two experiments. **, p < 0.01 when compared with non-immunized group (PBS).
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pntd.0003585.g003: Protective role of anti-ScaA immunity.(A) Anti-ScaA antibody inhibited O. tsutsugamushi infection into host cells. HeLa cells were infected with the pathogen in the presence of the indicated anti-Sca antibodies or nonimmune serum. At 4 h after infection, bacterial infection was examined using confocal microscopy after differential immunoflourescent staining (see materials and methods). (B) The O. tsutsugamushi per host cell ratio was determined from three independent experiments in (A). **, p < 0.01. (C) Survival curves of immunized mice following lethal challenge with O. tsutsugamushi. Mice (n = 5/group) were immunized with the indicated antigen from the Boryong strain and challenged intraperitoneally with 100 x LD50 of O. tsutsugamushi Boryong strain. Their survival was monitored until all the surviving mice recovered from the disease. This graph is a representative survival curve of two experiments. **, p < 0.01 when compared with non-immunized group (PBS).

Mentions: In order to confirm the neutralizing effect of anti-ScaA antibody on O. tsutsugamushi infection, HeLa cells were infected with the pathogen in the presence of various anti-Sca antibodies or nonimmune serum. At 4 h after infection, bacterial infection was examined by confocal microscopy after differential immunoflourescent staining and the O. tsutsugamushi/host cell ratio was determined (Fig. 3A and 3B). Presence of anti-ScaA antibody in the infection media significantly inhibited O. tsutsugamushi infection of host cells. The number of bacteria per cell was reduced by approximately 50% compared with the control group treated with nonimmune serum, whereas other anti-Sca antibodies failed to significantly inhibit bacterial infection, indicating that the anti-ScaA antibody could provide specific protective effect against bacterial infection.


Immunization with an autotransporter protein of Orientia tsutsugamushi provides protective immunity against scrub typhus.

Ha NY, Sharma P, Kim G, Kim Y, Min CK, Choi MS, Kim IS, Cho NH - PLoS Negl Trop Dis (2015)

Protective role of anti-ScaA immunity.(A) Anti-ScaA antibody inhibited O. tsutsugamushi infection into host cells. HeLa cells were infected with the pathogen in the presence of the indicated anti-Sca antibodies or nonimmune serum. At 4 h after infection, bacterial infection was examined using confocal microscopy after differential immunoflourescent staining (see materials and methods). (B) The O. tsutsugamushi per host cell ratio was determined from three independent experiments in (A). **, p < 0.01. (C) Survival curves of immunized mice following lethal challenge with O. tsutsugamushi. Mice (n = 5/group) were immunized with the indicated antigen from the Boryong strain and challenged intraperitoneally with 100 x LD50 of O. tsutsugamushi Boryong strain. Their survival was monitored until all the surviving mice recovered from the disease. This graph is a representative survival curve of two experiments. **, p < 0.01 when compared with non-immunized group (PBS).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4359152&req=5

pntd.0003585.g003: Protective role of anti-ScaA immunity.(A) Anti-ScaA antibody inhibited O. tsutsugamushi infection into host cells. HeLa cells were infected with the pathogen in the presence of the indicated anti-Sca antibodies or nonimmune serum. At 4 h after infection, bacterial infection was examined using confocal microscopy after differential immunoflourescent staining (see materials and methods). (B) The O. tsutsugamushi per host cell ratio was determined from three independent experiments in (A). **, p < 0.01. (C) Survival curves of immunized mice following lethal challenge with O. tsutsugamushi. Mice (n = 5/group) were immunized with the indicated antigen from the Boryong strain and challenged intraperitoneally with 100 x LD50 of O. tsutsugamushi Boryong strain. Their survival was monitored until all the surviving mice recovered from the disease. This graph is a representative survival curve of two experiments. **, p < 0.01 when compared with non-immunized group (PBS).
Mentions: In order to confirm the neutralizing effect of anti-ScaA antibody on O. tsutsugamushi infection, HeLa cells were infected with the pathogen in the presence of various anti-Sca antibodies or nonimmune serum. At 4 h after infection, bacterial infection was examined by confocal microscopy after differential immunoflourescent staining and the O. tsutsugamushi/host cell ratio was determined (Fig. 3A and 3B). Presence of anti-ScaA antibody in the infection media significantly inhibited O. tsutsugamushi infection of host cells. The number of bacteria per cell was reduced by approximately 50% compared with the control group treated with nonimmune serum, whereas other anti-Sca antibodies failed to significantly inhibit bacterial infection, indicating that the anti-ScaA antibody could provide specific protective effect against bacterial infection.

Bottom Line: Despite the wide range of preventative approaches that have been attempted in the past 70 years, all have failed to develop an effective prophylactic vaccine.Currently, the selection of the proper antigens is one of the critical barriers to generating cross-protective immunity against antigenically-variable strains of O. tsutsugamushi.Our findings demonstrate that ScaA functions as a bacterial adhesion factor, and anti-ScaA antibody significantly neutralizes bacterial infection of host cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.

ABSTRACT

Background: Scrub typhus is an acute febrile disease caused by Orientia tsutsugamushi infection. Recently, the rapid increase of scrub typhus incidence in several countries within the endemic region has become a serious public health issue. Despite the wide range of preventative approaches that have been attempted in the past 70 years, all have failed to develop an effective prophylactic vaccine. Currently, the selection of the proper antigens is one of the critical barriers to generating cross-protective immunity against antigenically-variable strains of O. tsutsugamushi.

Methodology/principal findings: We examined the potential role of ScaA protein, an autotransporter protein of O. tsutsugamushi, in bacterial pathogenesis and evaluated the protective attributes of ScaA immunization in lethal O. tsutsugamushi infection in mice. Our findings demonstrate that ScaA functions as a bacterial adhesion factor, and anti-ScaA antibody significantly neutralizes bacterial infection of host cells. In addition, immunization with ScaA not only provides protective immunity against lethal challenges with the homologous strain, but also confers significant protection against heterologous strains when combined with TSA56, a major outer membrane protein of O. tsutsugamushi.

Conclusions/significance: Immunization of ScaA proteins provides protective immunity in mice when challenged with the homologous strain and significantly enhanced protective immunity against infection with heterologous strains. To our knowledge, this is the most promising result of scrub typhus vaccination trials against infection of heterologous strains in mouse models thus far.

Show MeSH
Related in: MedlinePlus