Paraskevi Basdeki (Greece)
National and Kapodistrian University of Athens, Medical School Immunobiology and Vaccinology Research Laboratory, First Department of Paediatrics, ''Aghia Sophia'' Children's HospitalAuthor Of 1 Presentation
EVALUATION OF PROTECTIVE EFFICACY AND IMMUNOGENICITY OF EPITOPE-BASED PNEUMOCOCCAL VACCINE CANDIDATES USING SYNTHETIC VIRUS-LIKE PARTICLES (SVLPS) IN AN INTRAPERITONEAL SEPSIS MURINE MODEL
Abstract
Backgrounds:
We have previously identified 4 immunoreactive, linear B-cell epitopes within pneumococcal surface proteins (CbpD, PhtD, PhtE & ZmpB) that are highly conserved among different serotypes. These epitopes, emulsified in Freund’s Adjuvant, showed high immunogenicity and offered prolonged survival against murine pneumococcal sepsis. Herein, they were incorporated in SVLPs to improve survival rates and induce robust humoral immune responses without the need for external adjuvants.
Methods
Female BALB/c mice were subcutaneously immunized thrice at three-week intervals with synthetic 20mer peptides displayed on the surface of SVLPs. Positive controls received PCV13, while negative controls received the SVLP-carrier alone. Pneumococcal lethal sepsis was induced by 106 CFUs of an intraperitoneally administered serotype 3 clinical strain and survival was monitored. Sera were collected one day prior the second and third immunization and before the pneumococcal challenge. Antibody responses were assessed using ELISA.
Results:
Mice actively immunized with SVLP-conjugated synthetic peptides demonstrated enhanced survival against pneumococcal sepsis, compared to controls (p=0.005-0.04, Wilcoxon test). Five days after infection the survival rate was 100% for the positive control (PCV13), 66.7% for PhtE, 33.3% for CbpD, 16.7% for ZmpB and 0% for PhtD and the negative control (SVLPs), respectively. All immunized mice produced high levels of peptide-specific IgG antibodies. The difference in the endpoint titers, compared to controls, was statistically significant (p=0.0001-0.03, unpaired t-test). All immunized mice elicited gradually higher antibody titers upon receiving the booster immunizations.
Conclusions/Learning Points:
SVLP-conjugated synthetic epitopes are able to confer prolonged survival, compared to controls, associated with robust humoral immune responses. Further experiments are needed to assess the protective efficacy of the epitopes with the most promising characteristics in order for them to be considered as candidate antigens for novel pneumococcal vaccine formulations.
Presenter of 1 Presentation
EVALUATION OF PROTECTIVE EFFICACY AND IMMUNOGENICITY OF EPITOPE-BASED PNEUMOCOCCAL VACCINE CANDIDATES USING SYNTHETIC VIRUS-LIKE PARTICLES (SVLPS) IN AN INTRAPERITONEAL SEPSIS MURINE MODEL
Abstract
Backgrounds:
We have previously identified 4 immunoreactive, linear B-cell epitopes within pneumococcal surface proteins (CbpD, PhtD, PhtE & ZmpB) that are highly conserved among different serotypes. These epitopes, emulsified in Freund’s Adjuvant, showed high immunogenicity and offered prolonged survival against murine pneumococcal sepsis. Herein, they were incorporated in SVLPs to improve survival rates and induce robust humoral immune responses without the need for external adjuvants.
Methods
Female BALB/c mice were subcutaneously immunized thrice at three-week intervals with synthetic 20mer peptides displayed on the surface of SVLPs. Positive controls received PCV13, while negative controls received the SVLP-carrier alone. Pneumococcal lethal sepsis was induced by 106 CFUs of an intraperitoneally administered serotype 3 clinical strain and survival was monitored. Sera were collected one day prior the second and third immunization and before the pneumococcal challenge. Antibody responses were assessed using ELISA.
Results:
Mice actively immunized with SVLP-conjugated synthetic peptides demonstrated enhanced survival against pneumococcal sepsis, compared to controls (p=0.005-0.04, Wilcoxon test). Five days after infection the survival rate was 100% for the positive control (PCV13), 66.7% for PhtE, 33.3% for CbpD, 16.7% for ZmpB and 0% for PhtD and the negative control (SVLPs), respectively. All immunized mice produced high levels of peptide-specific IgG antibodies. The difference in the endpoint titers, compared to controls, was statistically significant (p=0.0001-0.03, unpaired t-test). All immunized mice elicited gradually higher antibody titers upon receiving the booster immunizations.
Conclusions/Learning Points:
SVLP-conjugated synthetic epitopes are able to confer prolonged survival, compared to controls, associated with robust humoral immune responses. Further experiments are needed to assess the protective efficacy of the epitopes with the most promising characteristics in order for them to be considered as candidate antigens for novel pneumococcal vaccine formulations.