Development of lactococcal GEM-based pneumococcal vaccines

Audouy, Sandrine; Selm, Saskia van; Roosmalen, Maarten L. van; Post, Eduard; Kanninga, Rolf; Neef, Jolanda; Estevão, Silvia; Nieuwenhuis, Edward E. S.; Adrian, Peter V.; Leenhouts, Kees; Hermans, Peter W. M.

doi:10.1016/j.vaccine.2006.09.026

Cited by 92 publications

(68 citation statements)

References 51 publications

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“…The dominant antigens identified from the xMAP bead assay may correspond to the dominant antigens seen on the immunoblots of whole-cell lysates, as PsaA has an estimated molecular mass of 33.7 kDa, and PpmA, CbpD, Ply, and PspA have estimated molecular masses of 35, 50.3, 52.5, and 62 kDa, respectively. The antigens included in the xMAP bead assays were largely pneumococcal surface proteins, many of which are conserved between strains and known to protect against invasive S. pneumoniae infections in animal models when used as protein vaccines (1,2,4,7,21,24). However, although vaccination with ⌬pab strains induced strong protection against subsequent infection with the homologous wild-type S. pneumoniae strain, vaccination with the ⌬pab strain failed, surprisingly, to induce biologically significantly protection against infection with heterologous strains, even after a two-dose vaccination schedule.…”

Section: Discussionmentioning

confidence: 99%

Infection with Conditionally Virulent Streptococcus pneumoniae Δ pab Strains Induces Antibody to Conserved Protein Antigens but Does Not Protect against Systemic Infection with Heterologous Strains

et al. 2011

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Avirulent strains of a bacterial pathogen could be useful tools for investigating immunological responses to infection and potentially effective vaccines. We have therefore constructed an auxotrophic TIGR4 ⌬pab strain of Streptococcus pneumoniae by deleting the pabB gene Sp_0665. The TIGR4 ⌬pab strain grew well in complete medium but was unable to grow in serum unless it was supplemented with para-aminobenzoic acid (PABA). The TIGR4 ⌬pab strain was markedly attenuated in virulence in mouse models of S. pneumoniae nasopharyngeal colonization, pneumonia, and sepsis. Supplementing mouse drinking water with PABA largely restored the virulence of TIGR4 ⌬pab. An additional ⌬pab strain constructed in the D39 capsular serotype 2 background was also avirulent in a sepsis model. Systemic inoculation of mice with TIGR4 ⌬pab induced antibody responses to S. pneumoniae protein antigens, including PpmA, PsaA, pneumolysin, and CbpD, but not capsular polysaccharide. Flow cytometry demonstrated that IgG in sera from TIGR4 ⌬pab-vaccinated mice bound to the surface of TIGR4 and D39 bacteria but not to a capsular serotype 3 strain, strain 0100993. Mice vaccinated with the TIGR4 ⌬pab or D39 ⌬pab strain by intraperitoneal inoculation were protected from developing septicemia when challenged with the homologous S. pneumoniae strain. Vaccination with the TIGR4 ⌬pab strain provided only weak or no protection against heterologous challenge with the D39 or 0100993 strain but did strongly protect against a TIGR4 capsular-switch strain expressing a serotype 2 capsule. The failure of cross-protection after systemic vaccination with ⌬pab bacteria suggests that parenteral administration of a live attenuated vaccine is not an attractive approach for preventing S. pneumoniae infection.

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Section: Discussionmentioning

confidence: 99%

Infection with Conditionally Virulent Streptococcus pneumoniae Δ pab Strains Induces Antibody to Conserved Protein Antigens but Does Not Protect against Systemic Infection with Heterologous Strains

et al. 2011

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“…S. pneumoniae has two to four zinc metalloproteinases depending on the strains. The best characterized of them is IgA1 protease, which is involved in pneumococcal adherence and colonization, and it could elicit significant protection against fatal pneumococcal pneumonia in mice (2,37). ZmpC has the capacity to cleave human matrix metalloproteinase-9 (MMP-9) and to stimulate syndecan-1 shedding (12,30), while the role of ZmpD in pneumococcal infection still is unknown.…”

Section: Discussionmentioning

confidence: 99%

Immunization with a ZmpB-Based Protein Vaccine Could Protect against Pneumococcal Diseases in Mice

Gong

Cui

et al. 2011

Infect Immun

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“…The development of immunity to one or more of these agents has the potential to protect against all of the pneumococcal serotypes that cause disease in humans. Trials of these vaccines in animal models, with vaccines administered orally, intranasally, and by injection, have shown them to be immunogenic and to be protective against IPD (3,4,15,36,44,73,111,114). One of the vaccines, IC47, which is a novel protein-based pneumococcal vaccine that contains 3 highly conserved proteins, has started phase I trials in 32 healthy adults.…”

Section: Vaccines In Developmentmentioning

confidence: 99%

Pediatric Invasive Pneumococcal Disease in the United States in the Era of Pneumococcal Conjugate Vaccines

2012

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SUMMARY Invasive infections caused by Streptococcus pneumoniae continue to be a major cause of morbidity and mortality worldwide, especially in children under 5 years of age. In the United States, 90% of invasive pneumococcal infections in children are caused by 13 serotypes of S. pneumoniae . The licensure (in 2000) and subsequent widespread use of a heptavalent pneumococcal conjugate vaccine (PCV7) have had a significant impact on decreasing the incidence of serious invasive pneumococcal disease (IPD) in all age groups, especially in children under 2 years of age. However, the emergence of replacement non-PCV7 serotypes, especially serotype 19A, has resulted in an increase in the incidence of serious and invasive infections. In 2010, a 13-valent PCV was licensed in the United States. However, the impact that this vaccine will have on IPD remains to be seen. The objectives of this review are to discuss the epidemiology of serious and invasive pneumococcal infections in the United States in the PCV era and to review some of the pneumococcal vaccines that are in development.

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Development of lactococcal GEM-based pneumococcal vaccines

Cited by 92 publications

References 51 publications

Infection with Conditionally Virulent Streptococcus pneumoniae Δ pab Strains Induces Antibody to Conserved Protein Antigens but Does Not Protect against Systemic Infection with Heterologous Strains

Infection with Conditionally Virulent Streptococcus pneumoniae Δ pab Strains Induces Antibody to Conserved Protein Antigens but Does Not Protect against Systemic Infection with Heterologous Strains

Immunization with a ZmpB-Based Protein Vaccine Could Protect against Pneumococcal Diseases in Mice

Pediatric Invasive Pneumococcal Disease in the United States in the Era of Pneumococcal Conjugate Vaccines

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