Safety and immunogenicity of pneumococcal protein vaccine candidates: Monovalent choline-binding protein A (PcpA) vaccine and bivalent PcpA–pneumococcal histidine triad protein D vaccine

Bologa, Monica; Kamtchoua, Thierry; Hopfer, Robert; Sheng, Xinjun; Hicks, Bryony; Bixler, Garvin S.; Hou, Victor C.; Pehlic, Vildana; Yuan, Tao; Gurunathan, Sanjay

doi:10.1016/j.vaccine.2012.10.076

Cited by 67 publications

(63 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We investigated a range of antigen dosages around those previously determined to be optimal in CB mice (personal communication from Sanofi Pasteur) and found the optimal doses (maximal IgG titers) to be similar, but not identical, in infant and adult mice for all three proteins. Alum was included as an adjuvant in all experiments described here because it is approved for use in humans and clinical trials and is included in current clinical trials with these proteins (19,24).…”

Section: Vaccination Dosage Optimizationmentioning

confidence: 99%

See 1 more Smart Citation

Contributions to Protection from Streptococcus pneumoniae Infection Using the Monovalent Recombinant Protein Vaccine Candidates PcpA, PhtD, and PlyD1 in an Infant Murine Model during Challenge

Verhoeven

Perry

Pichichero

2014

Clin. Vaccine Immunol.

View full text Add to dashboard Cite

A vaccine consisting of several conserved proteins with different functions directing the pathogenesis of pneumonia and sepsis would be preferred for protection against infection by Streptococcus pneumoniae. Infants will be the major population targeted for nextgeneration pneumococcal vaccines. Here, we investigated the potential efficacy provided by three recombinant pneumococcal vaccine candidate proteins-pneumococcal histidine triad D (PhtD), detoxified pneumolysin derivative (PlyD1), and pneumococcal choline-binding protein A (PcpA)-for reducing pneumonia and sepsis in an infant mouse vaccine model. We found vaccination with PhtD and PcpA provided high IgG antibody titers after vaccination in infant mice, similar to adult mice comparators. PlyD1-specific total IgG was significantly lower in infant mice, with minimal boosting with the second and third vaccinations. Similar isotypes of IgG for PhtD and PlyD1 were generated in infant compared to adult mice. Although lower total specific IgG to all three proteins was elicited in infant than in adult mice, the infant mice were protected from bacteremic pneumonia and sepsis mortality (PlyD1) and had lower lung bacterial burdens (PcpA and PhtD) after challenge. The observed immune responses coupled with bacterial reductions elicited by each of the monovalent proteins support further testing in human infant clinical trials.

show abstract

Section: Vaccination Dosage Optimizationmentioning

confidence: 99%

“…The mechanism of this protection may be antibody mediated, as interference with adhesion by antibodies derived from colonized human hosts can block binding to lungderived cell lines (12). A phase I study of PcpA in combination with PhtD showed that the bivalent vaccine was safe and immunogenic in human adults (24).…”

mentioning

confidence: 99%

Contributions to Protection from Streptococcus pneumoniae Infection Using the Monovalent Recombinant Protein Vaccine Candidates PcpA, PhtD, and PlyD1 in an Infant Murine Model during Challenge

Verhoeven

Perry

Pichichero

2014

Clin. Vaccine Immunol.

View full text Add to dashboard Cite

show abstract

“…Pneumococcal histidine triad protein D (PhtD) [13][14][15][16][17][18], pneumococcal choline binding protein A (PcpA) [15,17,19,20], and pneumolysin (Ply) [17,[21][22][23][24][25] are highly conserved, immunogenic and elicit protection against pneumococcal disease in animal models. PhtD is an especially attractive vaccine candidate due to its strong immunogenicity, efficacy in protection against nasopharyngeal colonization, and among the other pneumococcal histidine triad proteins in Spn, PhtD is the most highly conserved across pneumococcal serotypes [26,27].…”

Section: Introductionmentioning

confidence: 99%

Trivalent pneumococcal protein recombinant vaccine protects against lethal Streptococcus pneumoniae pneumonia and correlates with phagocytosis by neutrophils during early pathogenesis

Surendran

Verhoeven

et al. 2015

Vaccine

View full text Add to dashboard Cite

“…As a vaccine, we used S. pneumoniae histidine triad protein D (PhtD), a highly conserved, surface-exposed adhesin protein that facilitates attachment to the NP and lung epithelium cells (10)(11)(12). PhtD as a vaccine component has been shown to be protective in a number of mouse S. pneumoniae infection models (11,13,14) and is included in vaccines currently in human trials (15)(16)(17). In our current mouse study, the outcome of PhtD vaccinemediated prevention of invasive S. pneumoniae pathogenesis proved comparable to that achieved with PCV13 vaccination.…”

mentioning

confidence: 99%

Protection against Streptococcus pneumoniae Invasive Pathogenesis by a Protein-Based Vaccine Is Achieved by Suppression of Nasopharyngeal Bacterial Density during Influenza A Virus Coinfection

Khan

Pichichero

2017

Infect Immun

View full text Add to dashboard Cite

An increase in Streptococcus pneumoniae nasopharynx (NP) colonization density during a viral coinfection initiates pathogenesis. To mimic natural S. pneumoniae pathogenesis, we commensally colonized the NPs of adult C57BL/6 mice with S. pneumoniae serotype (ST) 6A or 8 and then coinfected them with mouseadapted H1N1 influenza A virus (PR/8/34). S. pneumoniae established effective commensal colonization, and influenza virus coinfection caused S. pneumoniae NP density to increase, resulting in bacteremia and mortality. We then studied histidine triad protein D (PhtD), an S. pneumoniae adhesin vaccine candidate, for its ability to prevent invasive S. pneumoniae disease in adult and infant mice. In adult mice, the efficacy of PhtD vaccination was compared with that of PCV13. Vaccination with PCV13 led to a greater reduction of S. pneumoniae NP density (Ͼ2.5 log units) than PhtD vaccination (ϳ1-log-unit reduction). However, no significant difference was observed with regard to the prevention of S. pneumoniae bacteremia, and there was no difference in mortality. Depletion of CD4 ϩ T cells in PhtD-vaccinated adult mice, but not PCV13-vaccinated mice, caused a loss of vaccine-induced protection. In infant mice, passive transfer of antisera or CD4 ϩ T cells from PhtD-vaccinated adult mice led to a nonsignificant reduction in NP colonization density, whereas passive transfer of antisera and CD4 ϩ T cells was needed to cause a significant reduction in NP colonization density. For the first time, these data show an outcome with regard to prevention of invasive S. pneumoniae pathogenesis with a protein vaccine similar to that which occurs with a glycoconjugate vaccine despite a less robust reduction in NP bacterial density.

show abstract

Safety and immunogenicity of pneumococcal protein vaccine candidates: Monovalent choline-binding protein A (PcpA) vaccine and bivalent PcpA–pneumococcal histidine triad protein D vaccine

Cited by 67 publications

References 25 publications

Contributions to Protection from Streptococcus pneumoniae Infection Using the Monovalent Recombinant Protein Vaccine Candidates PcpA, PhtD, and PlyD1 in an Infant Murine Model during Challenge

Contributions to Protection from Streptococcus pneumoniae Infection Using the Monovalent Recombinant Protein Vaccine Candidates PcpA, PhtD, and PlyD1 in an Infant Murine Model during Challenge

Trivalent pneumococcal protein recombinant vaccine protects against lethal Streptococcus pneumoniae pneumonia and correlates with phagocytosis by neutrophils during early pathogenesis

Protection against Streptococcus pneumoniae Invasive Pathogenesis by a Protein-Based Vaccine Is Achieved by Suppression of Nasopharyngeal Bacterial Density during Influenza A Virus Coinfection

Contact Info

Product

Resources

About