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Active Immunization with Extracellular Vesicles Derived from Staphylococcus aureus Effectively Protects against Staphylococcal Lung Infections, Mainly via Th1 Cell-Mediated Immunity.

Choi SJ, Kim MH, Jeon J, Kim OY, Choi Y, Seo J, Hong SW, Lee WH, Jeon SG, Gho YS, Jee YK, Kim YK - PLoS ONE (2015)

Bottom Line: In addition, these EVs have the vaccine adjuvant ability to induce protective immunity such as the up-regulation of co-stimulatory molecules and the expression of T cell polarizing cytokines in antigen-presenting cells.These protective effects were also found in mice that were adoptively transferred with splenic T cells isolated from S. aureus EV-immunized mice, but not in serum transferred mice.Furthermore, this protective effect of S. aureus EVs was significantly reduced by the absence of interferon-gamma, but not by the absence of interleukin-17.

View Article: PubMed Central - PubMed

Affiliation: Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.

ABSTRACT
Staphylococcus aureus is an important pathogenic bacterium that causes various infectious diseases. Extracellular vesicles (EVs) released from S. aureus contain bacterial proteins, nucleic acids, and lipids. These EVs can induce immune responses leading to similar symptoms as during staphylococcal infection condition and have the potential as vaccination agent. Here, we show that active immunization (vaccination) with S. aureus-derived EVs induce adaptive immunity of antibody and T cell responses. In addition, these EVs have the vaccine adjuvant ability to induce protective immunity such as the up-regulation of co-stimulatory molecules and the expression of T cell polarizing cytokines in antigen-presenting cells. Moreover, vaccination with S. aureus EVs conferred protection against lethality induced by airway challenge with lethal dose of S. aureus and also pneumonia induced by the administration of sub-lethal dose of S. aureus. These protective effects were also found in mice that were adoptively transferred with splenic T cells isolated from S. aureus EV-immunized mice, but not in serum transferred mice. Furthermore, this protective effect of S. aureus EVs was significantly reduced by the absence of interferon-gamma, but not by the absence of interleukin-17. Together, the study herein suggests that S. aureus EVs are a novel vaccine candidate against S. aureus infections, mainly via Th1 cellular response.

No MeSH data available.


Related in: MedlinePlus

Toxicity of SEV vaccine.Mice were intramuscularly administered with 5 μg or 50 μg of SEV and monitored for 14 days. (n = 10) (A) The survival rate, body temperature, and body weight of mice measured at indicated times. (B) The levels of IL-1β, IL-6 and TNF-α in serum of SEV- and sham (PBS)-immunized mice 24 h after the SEV administration. n.s. indicates not significant.
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pone.0136021.g008: Toxicity of SEV vaccine.Mice were intramuscularly administered with 5 μg or 50 μg of SEV and monitored for 14 days. (n = 10) (A) The survival rate, body temperature, and body weight of mice measured at indicated times. (B) The levels of IL-1β, IL-6 and TNF-α in serum of SEV- and sham (PBS)-immunized mice 24 h after the SEV administration. n.s. indicates not significant.

Mentions: Safety is the one of the important requirement to be considered when developing and controlling vaccine. Therefore, in order for the SEV vaccine to be developed for use clinically, toxicity is a critical issue that must be assured. To test the toxicity of SEVs immunization, mice were injected intramuscularly with SEVs of the dose used for immunization experiments and of 10 times higher. The survival rate, body temperature, and body weight were monitored for 14 days for examination of any inflammatory responses (Fig 8A). All of the mice survived after SEV administration. Moreover, all the mice injected with SEVs did not show any phenotypical difference compared to the sham-injected mice. In addition, we measured the blood serum cytokines after the SEV administration to evaluate the evidence of systemic inflammation (Fig 8B). As a result, there was no difference in the blood serum cytokine levels between the sham and SEVs administration groups. These results indicate that the administration of SEVs does not cause notable toxic effect on mice.


Active Immunization with Extracellular Vesicles Derived from Staphylococcus aureus Effectively Protects against Staphylococcal Lung Infections, Mainly via Th1 Cell-Mediated Immunity.

Choi SJ, Kim MH, Jeon J, Kim OY, Choi Y, Seo J, Hong SW, Lee WH, Jeon SG, Gho YS, Jee YK, Kim YK - PLoS ONE (2015)

Toxicity of SEV vaccine.Mice were intramuscularly administered with 5 μg or 50 μg of SEV and monitored for 14 days. (n = 10) (A) The survival rate, body temperature, and body weight of mice measured at indicated times. (B) The levels of IL-1β, IL-6 and TNF-α in serum of SEV- and sham (PBS)-immunized mice 24 h after the SEV administration. n.s. indicates not significant.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4558092&req=5

pone.0136021.g008: Toxicity of SEV vaccine.Mice were intramuscularly administered with 5 μg or 50 μg of SEV and monitored for 14 days. (n = 10) (A) The survival rate, body temperature, and body weight of mice measured at indicated times. (B) The levels of IL-1β, IL-6 and TNF-α in serum of SEV- and sham (PBS)-immunized mice 24 h after the SEV administration. n.s. indicates not significant.
Mentions: Safety is the one of the important requirement to be considered when developing and controlling vaccine. Therefore, in order for the SEV vaccine to be developed for use clinically, toxicity is a critical issue that must be assured. To test the toxicity of SEVs immunization, mice were injected intramuscularly with SEVs of the dose used for immunization experiments and of 10 times higher. The survival rate, body temperature, and body weight were monitored for 14 days for examination of any inflammatory responses (Fig 8A). All of the mice survived after SEV administration. Moreover, all the mice injected with SEVs did not show any phenotypical difference compared to the sham-injected mice. In addition, we measured the blood serum cytokines after the SEV administration to evaluate the evidence of systemic inflammation (Fig 8B). As a result, there was no difference in the blood serum cytokine levels between the sham and SEVs administration groups. These results indicate that the administration of SEVs does not cause notable toxic effect on mice.

Bottom Line: In addition, these EVs have the vaccine adjuvant ability to induce protective immunity such as the up-regulation of co-stimulatory molecules and the expression of T cell polarizing cytokines in antigen-presenting cells.These protective effects were also found in mice that were adoptively transferred with splenic T cells isolated from S. aureus EV-immunized mice, but not in serum transferred mice.Furthermore, this protective effect of S. aureus EVs was significantly reduced by the absence of interferon-gamma, but not by the absence of interleukin-17.

View Article: PubMed Central - PubMed

Affiliation: Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.

ABSTRACT
Staphylococcus aureus is an important pathogenic bacterium that causes various infectious diseases. Extracellular vesicles (EVs) released from S. aureus contain bacterial proteins, nucleic acids, and lipids. These EVs can induce immune responses leading to similar symptoms as during staphylococcal infection condition and have the potential as vaccination agent. Here, we show that active immunization (vaccination) with S. aureus-derived EVs induce adaptive immunity of antibody and T cell responses. In addition, these EVs have the vaccine adjuvant ability to induce protective immunity such as the up-regulation of co-stimulatory molecules and the expression of T cell polarizing cytokines in antigen-presenting cells. Moreover, vaccination with S. aureus EVs conferred protection against lethality induced by airway challenge with lethal dose of S. aureus and also pneumonia induced by the administration of sub-lethal dose of S. aureus. These protective effects were also found in mice that were adoptively transferred with splenic T cells isolated from S. aureus EV-immunized mice, but not in serum transferred mice. Furthermore, this protective effect of S. aureus EVs was significantly reduced by the absence of interferon-gamma, but not by the absence of interleukin-17. Together, the study herein suggests that S. aureus EVs are a novel vaccine candidate against S. aureus infections, mainly via Th1 cellular response.

No MeSH data available.


Related in: MedlinePlus