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Safety, reactogenicity and immunogenicity of two investigational pneumococcal protein-based vaccines: Results from a
Roman Prymula1, Leszek Szenborn2, Sven-Arne Silfverdal3
1Department of Social Medicine, Faculty of Medicine in Hradec Králové, Charles University in Prague, Šimkova 870, 500 38 Hradec Králové, Czech Republic.
Insights
New pneumococcal vaccines containing pneumolysin toxoid (dPly) and histidine-triad protein D (PhtD) were well-tolerated and immunogenic in infants. These investigational vaccines showed comparable safety and immune responses to existing vaccines.
Area of Science:
- Immunology
- Vaccinology
- Pediatrics
Background:
- Pneumococcal conjugate vaccines (PCVs) protect against Streptococcus pneumoniae.
- Protein-based antigens like pneumolysin toxoid (dPly) and histidine-triad protein D (PhtD) may enhance vaccine efficacy.
- Evaluating novel vaccine formulations is crucial for improving serotype-related protection.
Purpose of the Study:
- To assess the safety and immunogenicity of two investigational vaccines (PHiD-CV/dPly/PhtD-10 and PHiD-CV/dPly/PhtD-30) compared to a control vaccine (PHiD-CV) and a licensed vaccine (PCV13).
- To evaluate fever occurrences and serious adverse events following vaccination.
- To compare antibody levels against pneumococcal antigens (dPly, PhtD) and serotype-specific polysaccharides.
Main Methods:
- A phase II, multi-center, observer-blind trial (NCT01204658) involving infants.
- Infants were randomized to receive one of four vaccine groups: PHiD-CV/dPly/PhtD-10, PHiD-CV/dPly/PhtD-30, PHiD-CV, or PCV13.
- Vaccines were co-administered with DTPa-HBV-IPV/Hib at approximately 2, 3, 4, and 12-15 months of age.
Main Results:
- The non-inferiority objective for fever >40.0°C was met, with no vaccine-related cases reported during primary vaccination.
- Adverse event incidence was similar across PHiD-CV groups; serious adverse events varied by group but were generally low.
- PHiD-CV/dPly/PhtD-30 demonstrated superior anti-Ply and anti-PhtD antibody levels compared to PHiD-CV/dPly/PhtD-10 after dose 3.
- High antibody concentrations against most PHiD-CV serotypes were achieved in PHiD-CV/dPly/PhtD groups, with notable exceptions for serotypes 6B and 23F post-primary vaccination.
Conclusions:
- Investigational PHiD-CV/dPly/PhtD vaccines were well-tolerated and immunogenic in infants when co-administered with DTPa-HBV-IPV/Hib.
- Immune responses to serotype-specific, protein D, and co-administered antigens were not adversely affected compared to the PHiD-CV control group.
- These findings support the potential of incorporating pneumococcal protein antigens into conjugate vaccines to broaden protection.
Introduction:
Vaccination with formulations containing pneumococcal protein antigens such as pneumolysin toxoid (dPly) and histidine-triad protein D (PhtD) may extend serotype-related protection of pneumococcal conjugate vaccines (PCVs) against Streptococcus pneumoniae.
Methods:
This phase II, multi-center, observer-blind trial conducted in Europe (NCT01204658) assessed 2 investigational vaccines containing 10 serotype-specific polysaccharide conjugates of PHiD-CV and either 10 or 30µg of dPly and PhtD each. Infants randomized 1:1:1:1 received 4 doses of PHiD-CV/dPly/PhtD-10, PHiD-CV/dPly/PhtD-30, PHiD-CV, or 13-valent PCV (PCV13), co-administered with DTPa-HBV-IPV/Hib, at ages ∼2, 3, 4 and 12-15months. Occurrences of fever >40.0°C following primary vaccination with PHiD-CV/dPly/PhtD vaccines compared to PHiD-CV (non-inferiority objective), dose superiority, safety and immunogenicity were assessed.
Results:
575 children received primary vaccination, and 564 booster vaccination. The non-inferiority objective was met; no fever >40.0°C causally related to vaccination was reported during primary vaccination. Incidence of adverse events appeared similar between the 3 PHiD-CV groups. Serious adverse events were reported in 13, 9, 21 (1 related to vaccination), and 17 children in the PHiD-CV/dPly/PhtD-10, PHiD-CV/dPly/PhtD-30, PHiD-CV, and PCV13 groups, respectively. PHiD-CV/dPly/PhtD-30 was superior to PHiD-CV/dPly/PhtD-10 in terms of post-dose 3 anti-Ply and Anti-PhtD antibody levels. Anti-Ply and anti-PhtD antibody levels were higher in both PHiD-CV/dPly/PhtD groups than in controls and increased from post-primary to post-booster timepoint. Post-primary and booster vaccination, for each PHiD-CV serotype, ≥98.5% of participants in PHiD-CV/dPly/PhtD groups had antibody concentrations ≥ 0.2μg/mL, except for 6B (≥72.3%) and 23F (≥82.7%) post-primary vaccination. Similar results were observed in the PHiD-CV group. Immune responses to protein D and DTPa-HBV-IPV/Hib were within similar ranges for the 3 PHiD-CV groups.
Conclusion:
Both PHiD-CV/dPly/PhtD formulations co-administered with DTPa-HBV-IPV/Hib in infants were well-tolerated and immunogenic for dPly and PhtD antigens, while immune responses to serotype-specific, protein D and co-administered antigens did not appear altered in comparison to PHiD-CV group.
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