Safety and immunogenicity of a trivalent recombinant PcpA, PhtD, and PlyD1 pneumococcal protein vaccine in adults, toddlers, and infants: A phase I randomized controlled study

Brooks, W. Abdullah; Chang, Lee-Jah; Sheng, Xinjun; Hopfer, Robert

doi:10.1016/j.vaccine.2015.06.078

Cited by 54 publications

(40 citation statements)

References 15 publications

(28 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Another trivalent recombinant candidate vaccine that comprised PhtD, Ply and PcpA was reported by Brooks and colleagues [43]. The vaccine formulations increased antibodies concentrations in adults, toddlers, and infants to all vaccine antigens.…”

Section: Clinical Studiesmentioning

confidence: 96%

Next-Generation Whole-Cell Pneumococcal Vaccine

2019

View full text Add to dashboard Cite

Streptococcus pneumoniae remains a major public health hazard. Although Pneumococcal Conjugate Vaccines (PCVs) are available and have significantly reduced the rate of invasive pneumococcal diseases, there is still a need for new vaccines with unlimited serotype coverage, long-lasting protection, and lower cost to be developed. One of the most promising candidates is the Whole-Cell Pneumococcal Vaccine (WCV). The new generation of whole-cell vaccines is based on an unencapsulated serotype that allows the expression of many bacterial antigens at a lower cost than a recombinant vaccine. These vaccines have been extensively studied, are currently in human trial phase 1/2, and seem to be the best treatment choice for pneumococcal diseases, especially for developing countries.

show abstract

Section: Clinical Studiesmentioning

confidence: 96%

Next-Generation Whole-Cell Pneumococcal Vaccine

2019

View full text Add to dashboard Cite

show abstract

“…[69] Adults (18–50 yrs) and toddlers (12–13 mos.) received a single high dose injection of aluminum-adjuvanted PPrV.…”

Section: Pneumococcal Protein Vaccinesmentioning

confidence: 99%

“…The vaccine was safe and well tolerated and 75% or more of all PPrV + adjuvanted subjects had a ≥2-fold increase in serum antibody to all three antigens. [69]…”

Section: Pneumococcal Protein Vaccinesmentioning

confidence: 99%

Pneumococcal whole-cell and protein-based vaccines: changing the paradigm

Pichichero

2017

Expert Review of Vaccines

View full text Add to dashboard Cite

Introduction. Epidemiologic evaluations of Streptococcus pneumoniae nasopharyngeal (NP) colonization and pneumococcal disease suggest that newer serotypes in future formulations of pneumococcal conjugate vaccines (PCVs) are needed and there may need to be continued reformulations because there are many new emerging serotypes expressed by pneumococci. Areas Covered: Mechanisms of protection by next-generation whole-cell vaccine (WCV) and/or multi-component pneumococcal purified protein vaccines (PPVs) in development for prevention of pneumococcal infections. Expert Commentary: A long-term strategy for prevention of pneumococcal disease will likely include WCV and PPVs. However these vaccines will impact disease pathogenesis in a different manner than PCVs. Prevention of pneumococcal NP colonization should not be expected, nor is it desirable because risks for NP colonization by other replacement organisms into the ecological niche vacated by all pneumococci may have consequences. The expression biology of capsule and surface protein antigens are phase dependent. Therefore, the immune response will be different and the mechanism of protection divergent. WCVs and PPVs may be alternative strategies in low income developing countries to protect against invasive disease and reduce NP carriage load.

show abstract

“…Although the role of capsule and other pneumococcal virulence factors in the host response during infection has been investigated, little is known about the role of PcpA during pneumonia and invasive pneumococcal disease (IPD). PcpA [6-9], a choline binding protein, is considered an excellent candidate for inclusion into a pneumococcal protein vaccine [10]. This surface antigen is not produced under the high Mn2+ concentrations present in the nasopharynx [8] and antibody to PcpA does not protect against colonization [9].…”

Section: Introductionmentioning

confidence: 99%

PcpA Promotes Higher Levels of Infection and Modulates Recruitment of Myeloid-Derived Suppressor Cells during Pneumococcal Pneumonia

Walker

Novak

Widener

et al. 2016

The Journal of Immunology

View full text Add to dashboard Cite

We used two different infection models to investigate the kinetics of the PcpA-dependent pneumococcal disease in mice. In a bacteremic pneumonia model, we observed a PcpA-dependent increase in bacterial burden in the lungs, blood, liver, BAL and spleens of mice at 24-hrs post infection. This PcpA-dependent effect on bacterial burden appeared earlier (within 12-hrs) in the focal-pneumonia model, which lacks bacteremia or sepsis. Histological changes show that the ability of pneumococci to make PcpA was associated with unresolved inflammation in both models of infection. Using our bacteremic pneumonia model we further investigated the effects of PcpA on recruitment of innate immune regulatory cells. The presence of PcpA was associated with increased IL-6 levels, suppressed production of TNF-related apoptosis - inducing ligand (TRAIL) and reduced infiltration of polymorphonuclear cells. The ability of pneumococci to make PcpA negatively modulated both the infiltration and apoptosis of macrophages and the recruitment of myeloid-derived suppressor-like cells (MDSCs). The latter have been shown to facilitate clearance and control of bacterial pneumonia. Taken together, the ability to make PcpA was strongly associated with increased bacterial burden, inflammation and negative regulation of innate immune cell recruitment to the lung tissue during bacteremic pneumonia.

show abstract

Safety and immunogenicity of a trivalent recombinant PcpA, PhtD, and PlyD1 pneumococcal protein vaccine in adults, toddlers, and infants: A phase I randomized controlled study

Cited by 54 publications

References 15 publications

Next-Generation Whole-Cell Pneumococcal Vaccine

Next-Generation Whole-Cell Pneumococcal Vaccine

Pneumococcal whole-cell and protein-based vaccines: changing the paradigm

PcpA Promotes Higher Levels of Infection and Modulates Recruitment of Myeloid-Derived Suppressor Cells during Pneumococcal Pneumonia

Contact Info

Product

Resources

About