Limits...
Complete Protection against Pneumonic and Bubonic Plague after a Single Oral Vaccination.

Derbise A, Hanada Y, Khalifé M, Carniel E, Demeure CE - PLoS Negl Trop Dis (2015)

Bottom Line: This candidate vaccine however failed to confer full protection against bubonic plague and did not produce F1 stably.It involved cells with a Th1-Th17 effector profile, producing IFNγ, IL-17, and IL-10.To our knowledge, VTnF1 is the only plague vaccine ever reported that could provide high and durable protection against the two forms of plague after a single oral administration.

View Article: PubMed Central - PubMed

Affiliation: Unité de recherche Yersinia, Institut Pasteur, Paris, France.

ABSTRACT

Background: No efficient vaccine against plague is currently available. We previously showed that a genetically attenuated Yersinia pseudotuberculosis producing the Yersinia pestis F1 antigen was an efficient live oral vaccine against pneumonic plague. This candidate vaccine however failed to confer full protection against bubonic plague and did not produce F1 stably.

Methodology/principal findings: The caf operon encoding F1 was inserted into the chromosome of a genetically attenuated Y. pseudotuberculosis, yielding the VTnF1 strain, which stably produced the F1 capsule. Given orally to mice, VTnF1 persisted two weeks in the mouse gut and induced a high humoral response targeting both F1 and other Y. pestis antigens. The strong cellular response elicited was directed mostly against targets other than F1, but also against F1. It involved cells with a Th1-Th17 effector profile, producing IFNγ, IL-17, and IL-10. A single oral dose (108 CFU) of VTnF1 conferred 100% protection against pneumonic plague using a high-dose challenge (3,300 LD50) caused by the fully virulent Y. pestis CO92. Moreover, vaccination protected 100% of mice from bubonic plague caused by a challenge with 100 LD50 Y. pestis and 93% against a high-dose infection (10,000 LD50). Protection involved fast-acting mechanisms controlling Y. pestis spread out of the injection site, and the protection provided was long-lasting, with 93% and 50% of mice surviving bubonic and pneumonic plague respectively, six months after vaccination. Vaccinated mice also survived bubonic and pneumonic plague caused by a high-dose of non-encapsulated (F1-) Y. pestis.

Significance: VTnF1 is an easy-to-produce, genetically stable plague vaccine candidate, providing a highly efficient and long-lasting protection against both bubonic and pneumonic plague caused by wild type or un-encapsulated (F1-negative) Y. pestis. To our knowledge, VTnF1 is the only plague vaccine ever reported that could provide high and durable protection against the two forms of plague after a single oral administration.

No MeSH data available.


Related in: MedlinePlus

Humoral immune response induced by vaccination.(A) The antibody production induced by VTnF1 vaccination (108 CFU) was quantified at various days post vaccination using an ELISA measuring IgG directed against purified F1 antigen. Shown are the means ± sem of titers observed in two experiments performed during the first month post-vaccination (Exp.1, 7 mice) and during the six-months post-vaccination period (Exp.2, 14 mice). Mean IgG titers at each time point were compared statistically to that on day zero using the Mann-Whitney test, and all were significantly higher (p<0.001), except those on day 1. (B) The different Ig mouse isotypes present in sera were analyzed at sequential times. (C) The IgG response against antigens other than F1 was analyzed by ELISA against a Y. pestis CO92Δcaf sonicate, and (D) by western blotting. The Y. pestis CO92 wild type or CO92Δcaf (noted F1-) were used as source of blotted antigens and sera pooled either from naive mice or mice vaccinated 30 days earlier (noted VTnF1). The Caf1 band is indicated by an asterisk and the Caf1M band by a triangle. (E) The response against purified Yops was also analyzed by ELISA. Shown are results from 14 individual animals (dots), and group medians (horizontal line). The Mann-Whitney test was used for statistical analysis: ***: p<0.001.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4608741&req=5

pntd.0004162.g003: Humoral immune response induced by vaccination.(A) The antibody production induced by VTnF1 vaccination (108 CFU) was quantified at various days post vaccination using an ELISA measuring IgG directed against purified F1 antigen. Shown are the means ± sem of titers observed in two experiments performed during the first month post-vaccination (Exp.1, 7 mice) and during the six-months post-vaccination period (Exp.2, 14 mice). Mean IgG titers at each time point were compared statistically to that on day zero using the Mann-Whitney test, and all were significantly higher (p<0.001), except those on day 1. (B) The different Ig mouse isotypes present in sera were analyzed at sequential times. (C) The IgG response against antigens other than F1 was analyzed by ELISA against a Y. pestis CO92Δcaf sonicate, and (D) by western blotting. The Y. pestis CO92 wild type or CO92Δcaf (noted F1-) were used as source of blotted antigens and sera pooled either from naive mice or mice vaccinated 30 days earlier (noted VTnF1). The Caf1 band is indicated by an asterisk and the Caf1M band by a triangle. (E) The response against purified Yops was also analyzed by ELISA. Shown are results from 14 individual animals (dots), and group medians (horizontal line). The Mann-Whitney test was used for statistical analysis: ***: p<0.001.

Mentions: The humoral immune response elicited by vaccination with VTnF1 (108 CFU orally) was first evaluated by quantifying serum antibodies against purified F1 at different times post-vaccination over a period of six months. Anti-F1 IgG were detectable as early as four days after vaccination, and reached plateau values after 7 days (Fig 3A). They then maintained at high levels without significant evolution, as shown by the fact that titers observed after six months (d180) were not significantly different from those at d30 (p = 0.08, 14 mice per group). Analysis of the immunoglobulin isotypes revealed that both IgG1, IgG2a, IgG2b and IgG3 contributed to this humoral response, whereas IgM peaked rapidly after vaccination and then fell to low levels (Fig 3B).


Complete Protection against Pneumonic and Bubonic Plague after a Single Oral Vaccination.

Derbise A, Hanada Y, Khalifé M, Carniel E, Demeure CE - PLoS Negl Trop Dis (2015)

Humoral immune response induced by vaccination.(A) The antibody production induced by VTnF1 vaccination (108 CFU) was quantified at various days post vaccination using an ELISA measuring IgG directed against purified F1 antigen. Shown are the means ± sem of titers observed in two experiments performed during the first month post-vaccination (Exp.1, 7 mice) and during the six-months post-vaccination period (Exp.2, 14 mice). Mean IgG titers at each time point were compared statistically to that on day zero using the Mann-Whitney test, and all were significantly higher (p<0.001), except those on day 1. (B) The different Ig mouse isotypes present in sera were analyzed at sequential times. (C) The IgG response against antigens other than F1 was analyzed by ELISA against a Y. pestis CO92Δcaf sonicate, and (D) by western blotting. The Y. pestis CO92 wild type or CO92Δcaf (noted F1-) were used as source of blotted antigens and sera pooled either from naive mice or mice vaccinated 30 days earlier (noted VTnF1). The Caf1 band is indicated by an asterisk and the Caf1M band by a triangle. (E) The response against purified Yops was also analyzed by ELISA. Shown are results from 14 individual animals (dots), and group medians (horizontal line). The Mann-Whitney test was used for statistical analysis: ***: p<0.001.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4608741&req=5

pntd.0004162.g003: Humoral immune response induced by vaccination.(A) The antibody production induced by VTnF1 vaccination (108 CFU) was quantified at various days post vaccination using an ELISA measuring IgG directed against purified F1 antigen. Shown are the means ± sem of titers observed in two experiments performed during the first month post-vaccination (Exp.1, 7 mice) and during the six-months post-vaccination period (Exp.2, 14 mice). Mean IgG titers at each time point were compared statistically to that on day zero using the Mann-Whitney test, and all were significantly higher (p<0.001), except those on day 1. (B) The different Ig mouse isotypes present in sera were analyzed at sequential times. (C) The IgG response against antigens other than F1 was analyzed by ELISA against a Y. pestis CO92Δcaf sonicate, and (D) by western blotting. The Y. pestis CO92 wild type or CO92Δcaf (noted F1-) were used as source of blotted antigens and sera pooled either from naive mice or mice vaccinated 30 days earlier (noted VTnF1). The Caf1 band is indicated by an asterisk and the Caf1M band by a triangle. (E) The response against purified Yops was also analyzed by ELISA. Shown are results from 14 individual animals (dots), and group medians (horizontal line). The Mann-Whitney test was used for statistical analysis: ***: p<0.001.
Mentions: The humoral immune response elicited by vaccination with VTnF1 (108 CFU orally) was first evaluated by quantifying serum antibodies against purified F1 at different times post-vaccination over a period of six months. Anti-F1 IgG were detectable as early as four days after vaccination, and reached plateau values after 7 days (Fig 3A). They then maintained at high levels without significant evolution, as shown by the fact that titers observed after six months (d180) were not significantly different from those at d30 (p = 0.08, 14 mice per group). Analysis of the immunoglobulin isotypes revealed that both IgG1, IgG2a, IgG2b and IgG3 contributed to this humoral response, whereas IgM peaked rapidly after vaccination and then fell to low levels (Fig 3B).

Bottom Line: This candidate vaccine however failed to confer full protection against bubonic plague and did not produce F1 stably.It involved cells with a Th1-Th17 effector profile, producing IFNγ, IL-17, and IL-10.To our knowledge, VTnF1 is the only plague vaccine ever reported that could provide high and durable protection against the two forms of plague after a single oral administration.

View Article: PubMed Central - PubMed

Affiliation: Unité de recherche Yersinia, Institut Pasteur, Paris, France.

ABSTRACT

Background: No efficient vaccine against plague is currently available. We previously showed that a genetically attenuated Yersinia pseudotuberculosis producing the Yersinia pestis F1 antigen was an efficient live oral vaccine against pneumonic plague. This candidate vaccine however failed to confer full protection against bubonic plague and did not produce F1 stably.

Methodology/principal findings: The caf operon encoding F1 was inserted into the chromosome of a genetically attenuated Y. pseudotuberculosis, yielding the VTnF1 strain, which stably produced the F1 capsule. Given orally to mice, VTnF1 persisted two weeks in the mouse gut and induced a high humoral response targeting both F1 and other Y. pestis antigens. The strong cellular response elicited was directed mostly against targets other than F1, but also against F1. It involved cells with a Th1-Th17 effector profile, producing IFNγ, IL-17, and IL-10. A single oral dose (108 CFU) of VTnF1 conferred 100% protection against pneumonic plague using a high-dose challenge (3,300 LD50) caused by the fully virulent Y. pestis CO92. Moreover, vaccination protected 100% of mice from bubonic plague caused by a challenge with 100 LD50 Y. pestis and 93% against a high-dose infection (10,000 LD50). Protection involved fast-acting mechanisms controlling Y. pestis spread out of the injection site, and the protection provided was long-lasting, with 93% and 50% of mice surviving bubonic and pneumonic plague respectively, six months after vaccination. Vaccinated mice also survived bubonic and pneumonic plague caused by a high-dose of non-encapsulated (F1-) Y. pestis.

Significance: VTnF1 is an easy-to-produce, genetically stable plague vaccine candidate, providing a highly efficient and long-lasting protection against both bubonic and pneumonic plague caused by wild type or un-encapsulated (F1-negative) Y. pestis. To our knowledge, VTnF1 is the only plague vaccine ever reported that could provide high and durable protection against the two forms of plague after a single oral administration.

No MeSH data available.


Related in: MedlinePlus