Effect of homologous and heterologous prime–boost on the immune response to recombinant plague antigens

Glynn, Audrey; Freytag, Lucy C.; Clements, John D.

doi:10.1016/j.vaccine.2004.10.025

Cited by 45 publications

(35 citation statements)

References 49 publications

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“…Glynn et al recently reported that using a "heterologous" boosting regimen (i.n. prime and subcutaneous or transcutaneous boost of rF1-V in combination with LTR192G) elicited high titers to the rF1-V fusion protein in both sera and lung lavage of mice [6]. However, separate titers to F1 and V were only assessed in sera but not the lung and protection against challenge with Y. pestis was not reported.…”

Section: Resultsmentioning

confidence: 98%

“…Live, attenuated vaccines protect well against bubonic and pneumonic plague, but there have been adverse events associated with their use [2]. Subunit vaccines, developed from antigenic components of Y. pestis, in contrast, can successfully protect against both bubonic and pneumonic plague, and these vaccine products appear to be safe in animal models [6][7][8][9][10][11][12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Respiratory immunity is an important component of protection elicited by subunit vaccination against pneumonic plague

Reed

Martinez

2006

Vaccine

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Section: Resultsmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Respiratory immunity is an important component of protection elicited by subunit vaccination against pneumonic plague

Reed

Martinez

2006

Vaccine

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“…Although this self-association is due mainly to the F1 subcomponent, the fusion architecture actually reduces polydispersity compared to the individual F1 protein, which is even more aggregative [6]. Thus, the F1-V fusion based plague antigen is at the forefront of plague vaccine development [23][24][25][26]. As demonstrated by the findings reported herein, we propose that use of the described F1-V C424S protein form should facilitate the enhanced production and stability of F1-V-based plague vaccines.…”

Section: Discussionmentioning

confidence: 99%

Purification and protective efficacy of monomeric and modified Yersinia pestis capsular F1-V antigen fusion proteins for vaccination against plague

Goodin

Nellis

Powell

et al. 2007

Protein Expression and Purification

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The F1-V vaccine antigen, protective against Yersinia pestis, exhibits a strong tendency to multimerize that affects larger-scale manufacture and characterization. In this work, the sole F1-V cysteine was replaced with serine by site-directed mutagenesis for characterization of F1-V noncovalent multimer interactions and protective potency without participation by disulfide-linkages. F1-V and F1-V C424S proteins were over-expressed in Escherichia coli, recovered using mechanical lysis/pH-modulation and purified from urea-solubilized soft inclusion bodies, using successive ionexchange, ceramic hydroxyapatite, and size-exclusion chromatography. This purification method resulted in up to 2 mg per gram of cell paste of 95% pure, mono-disperse protein having ≤ 0.5 endotoxin units per mg by a kinetic chromogenic limulus amoebocyte lysate reactivity assay. Both F1-V and F1-V C424S were monomeric at pH 10.0 and progressively self-associated as pH conditions decreased to pH 6.0. Solution additives were screened for their ability to inhibit F1-V self-association at pH 6.5. An L-arginine buffer provided the greatest stabilizing effect. Conversion to >500-kDa multimers occurred between pH 6.0 and 5.0. Conditions for efficient F1-V adsorption to the cGMPcompatible Alhydrogel® adjuvant were optimized. Side-by-side evaluation for protective potency against subcutaneous plague infection in mice was conducted for F1-V C424S monomer; cysteinecapped F1-V monomer; cysteine-capped F1-V multimer; and a F1-V standard reported previously. After a two-dose vaccination with 2 × 20 µg of F1-V, respectively, 100, 80, 80, and 70% of injected mice survived a subcutaneous lethal plague challenge with 10 8 LD 50 Y. pestis CO92. Thus, vaccination with F1-V monomer and multimeric forms resulted in significant, and essentially equivalent, protection.

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“…Individual serum and BAL samples were examined for anti-F1-V total IgG, IgG1, and IgG2a antibodies using a quantitative ELISA as described previously [10]. For quantitative analysis, concentrations of IgG, IgG1, and IgG2a were determined by non-linear regression from a standard curve of mouse myeloma IgG1 or IgG2a (Sigma) serially diluted as a standard on each ELISA plate.…”

Section: Measurement Of Serum and Bal Antibodymentioning

confidence: 99%

“…In a recent study, we evaluated different prime -boost regimens, including parenteral, mucosal, and transcutaneous delivery, in order to explore the effect of changing the route of prime and boost on the ability of the recombinant Yersinia pestis-derived fusion protein (F1-V) to promote the development of long-lasting, high titer antibodies [10]. F1-V has been shown to provide protection against flea-borne, subcutaneous and aerosol challenge and has the potential to provide protective immunity against pneumonic as well as bubonic plague due to either wild type F1 + Y. pestis or to naturally occurring F1 -variants [11,12].…”

Section: Introductionmentioning

confidence: 99%

Effect of adjuvants and route of immunizations on the immune response to recombinant plague antigens

Uddowla

Freytag

Clements

2007

Vaccine

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In this study, we compare four different adjuvants, LT(R192G), CpG ODN, MPL ® TDM and alum, for their ability to affect the magnitude, distribution, and duration of antibody responses against F1-V, the lead-candidate antigen for the next generation vaccine against plague, in a murine model. In addition, three different routes of immunization -intranasal (IN), transcutaneous (TC), and subcutaneous (SC), were compared with each adjuvant. Since aerosol exposure to biological warfare agents is of primary concern, both serum and bronchioalveolar lavage (BAL) were analyzed for antigen-specific antibody responses. The most significant findings of the study reported here are that 1) the adjuvant influences the Type 1/Type 2 balance of the antibody response in both the serum and BAL, 2) mucosal immunization is not necessary to obtain F1-V-specific BAL responses, 3) nontraditional adjuvants such as LT(R192G) work when delivered SC, 4) the route of immunization affects the magnitude of the immune response, and 5) F1-V is highly immunogenic by some routes even in the absence of an exogenously applied adjuvant. These studies provide important insights into the influence of different classes of adjuvants on the immune outcome in biodefense vaccines and for development of new generation vaccines against other pathogens as well.

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Effect of homologous and heterologous prime–boost on the immune response to recombinant plague antigens

Cited by 45 publications

References 49 publications

Respiratory immunity is an important component of protection elicited by subunit vaccination against pneumonic plague

Respiratory immunity is an important component of protection elicited by subunit vaccination against pneumonic plague

Purification and protective efficacy of monomeric and modified Yersinia pestis capsular F1-V antigen fusion proteins for vaccination against plague

Effect of adjuvants and route of immunizations on the immune response to recombinant plague antigens

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