A bivalent vaccine to protect against Streptococcus pneumoniae and Salmonella typhi

Lu, Ying‐Jie; Zhang, Fan; Sayeed, Sabina; Thompson, Claudette M.; Szu, Shousun C.; Anderson, Patrick L.; Malley, Richard

doi:10.1016/j.vaccine.2012.03.039

Cited by 15 publications

(12 citation statements)

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“…As an immunogen, Dpr has been tested in different pneumococcal animal models and shown to confer protection against pneumococcal colonization and invasive diseases (45)(46)(47). This study thus provides additional evidence for an important role of Dpr in pneumococcal pathogenesis.…”

Section: Discussionmentioning

confidence: 74%

Effect of Nonheme Iron-Containing Ferritin Dpr in the Stress Response and Virulence of Pneumococci

et al. 2014

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bStreptococcus pneumoniae (pneumococcus) produces hydrogen peroxide as a by-product of metabolism and provides a competitive advantage against cocolonizing bacteria. As pneumococci do not produce catalase or an inducible regulator of hydrogen peroxide, the mechanism of resistance to hydrogen peroxide is unclear. A gene responsible for resistance to hydrogen peroxide and iron in other streptococci is that encoding nonheme iron-containing ferritin, dpr, but previous attempts to study this gene in pneumococcus by generating a dpr mutant were unsuccessful. In the current study, we found that dpr is in an operon with the downstream genes dhfr and clpX. We generated a dpr deletion mutant which displayed normal early-log-phase and mid-logphase growth in bacteriologic medium but survived less well at stationary phase; the addition of catalase partially rescued the growth defect. We showed that the dpr mutant is significantly more sensitive to pH, heat, iron concentration, and oxidative stress due to hydrogen peroxide. Using a mouse model of colonization, we also showed that the dpr mutant displays a reduced ability to colonize and is more rapidly cleared from the nasopharynx. Our results thus suggest that Dpr is important for pneumococcal resistance to stress and for nasopharyngeal colonization.

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Section: Discussionmentioning

confidence: 74%

Effect of Nonheme Iron-Containing Ferritin Dpr in the Stress Response and Virulence of Pneumococci

et al. 2014

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“…The absence of an adjuvant should facilitate licensure by simplifying the regulatory pathway. Other investigators have conjugated pneumococcal protein antigens to Vi [28], however, conjugation to Vi did not improve the IgG antibody response to the carrier proteins. The reason for the improved immunogenicity of the carrier protein in our study is not known but may be related to the Vi produced at IVI or to conjugation methodology used at IVI.…”

Section: Discussionmentioning

confidence: 89%

Preparation and testing of a Vi conjugate vaccine using pneumococcal surface protein A (PspA) from Streptococcus pneumoniae as the carrier protein

Kothari

Genschmer

Kothari

et al. 2014

Vaccine

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“…It is conceivable that development of a pneumococcal protein subunit vaccine would contain several antigens and/or be formulated with different or novel adjuvants, or perhaps as a fusion-conjugate [21] to improve immunogenicity and facilitate parenteral administration. Fusion conjugates comprised of the proteins identified here with either pneumococcal cell wall polysaccharide or Salmonella typhi Vi polysaccharide to provide protection against pneumococcal and/or S. typhi diseases are currently under investigation within our laboratory [22] .…”

Section: Discussionmentioning

confidence: 99%

Identification of Protective Pneumococcal TH17 Antigens from the Soluble Fraction of a Killed Whole Cell Vaccine

Moffitt

Malley

2012

PLoS ONE

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Mucosal or parenteral immunization with a killed unencapsulated pneumococcal whole cell antigen (WCA) with an adjuvant protects mice from colonization by a TH17 CD4+ cell-mediated mechanism. Using preparative SDS gels, we separated the soluble proteins that compose the WCA in order to identify fractions that were immunogenic and protective. We screened these fractions for their ability to stimulate IL-17A secretion from splenocytes obtained from mice immunized with WCA and adjuvant. We identified 12 proteins within the stimulatory fractions by mass spectrometry; these proteins were then cloned, recombinantly expressed and purified using an Escherichia coli expression system. The ability of these proteins to induce IL-17A secretion was then evaluated by stimulation of mouse splenocytes. Of the four most stimulatory proteins, three were protective in a mouse pneumococcal serotype 6B colonization model. This work thus describes a method for identifying immunogenic proteins from the soluble fraction of pneumococcus and shows that several of the proteins identified protect mice from colonization when used as mucosal vaccines. We propose that, by providing protection against pneumococcal colonization, one or more of these proteins may serve as components of a multivalent pneumococcal vaccine.

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A bivalent vaccine to protect against Streptococcus pneumoniae and Salmonella typhi

Cited by 15 publications

References 50 publications

Effect of Nonheme Iron-Containing Ferritin Dpr in the Stress Response and Virulence of Pneumococci

Effect of Nonheme Iron-Containing Ferritin Dpr in the Stress Response and Virulence of Pneumococci

Preparation and testing of a Vi conjugate vaccine using pneumococcal surface protein A (PspA) from Streptococcus pneumoniae as the carrier protein

Identification of Protective Pneumococcal TH17 Antigens from the Soluble Fraction of a Killed Whole Cell Vaccine

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