Objectives: This study aimed to evaluate the immunogenicity and safety of a 13-valent pneumococcal polysaccharide conjugate vaccine (CRM197/TT) (PCV13i) in infants. Methods: A total of 1200 infants were randomly assigned to either the experimental PCV13i group or the control PCV13 group in a 1:1 ratio. Each group received a three-dose series of the vaccine at 2, 4, and 6 months of age, followed by a booster dose at 12–15 months. Blood samples were collected before and 30 days after both primary and booster vaccinations. The primary immunogenicity endpoints were the seropositive rate and the geometric mean concentration (GMC) of IgG antibodies against the 13 pneumococcal serotypes. The primary safety endpoint was the incidence of adverse reactions within 0–7 days and 0–30 days after vaccination. Results: Results showed that the experimental PCV13i was well tolerated, with a safety profile comparable to that of the control vaccine. Following primary vaccination, the GMCs of IgG responses against serotypes 1, 5, 6A, 6B, 14, and 18C in the experimental group were lower than those in the control group, while responses against serotypes 3, 4, 7F, 9V, 19A, 19F, and 23F were higher. The experimental group exhibited higher opsonophagocytic killing assay (OPA) geometric mean titers (GMTs) for serotypes 3, 7F, 19A, and 19F compared to the control group, while GMTs for serotypes 1, 5, 6A, and 18C were lower. Following booster vaccination, OPA GMTs of the experimental group remained higher than those of the control group for serotypes 3, 7F, and 19F, while GMTs for serotype 5 were lower. Both vaccines induced robust immune responses, with high seropositive rates and significant increases in antibody levels following vaccination. Conclusions: The experimental PCV13i demonstrated non-inferiority to the control PCV13 in terms of immunogenicity.

Background: Pneumococcal diseases remain a global threat due to the serotype-specific limitations of polysaccharide vaccines. This study evaluated a recombinant protein-based pneumococcal vaccine (PBPV) combining three PspA variants (PRX1/Family1Clade2, P3296/Family2/Clade3, P5668/Family2/Clade4) and detoxified pneumolysin (PlyLD). PspA targets conserved surface epitopes to block immune evasion and achieve broad coverage, while PlyLD neutralizes pore-forming toxins and enhances adaptive immunity. Methods: We evaluated the safety and immunogenicity of the PBPV in animal models. Acute toxicity studies were conducted by administering a single intramuscular injection to ICR mice, whereas chronic toxicity and immunogenicity studies were performed in cynomolgus monkeys via repeated intramuscular injections, with an equal number of male and female animals in both groups. Immune responses were assessed using ELISA, multiplexed opsonophagocytic killing assays (MOPAs), and neutralizing antibody assays. Results: Acute toxicity studies in ICR mice showed no signs of abnormal toxicity or irritation at one-dose levels. In the chronic toxicity study, cynomolgus monkeys received repeated intramuscular injections once every 3 weeks for a total of four administrations, at doses of one dose/monkey and five doses/monkey, followed by a 4-week recovery period. No significant systemic toxic reactions were observed, and the safe dose was determined to be five doses/monkey. In the immunogenicity study of monkey serum, both low-dose and high-dose groups demonstrated significant increases in antigen-specific IgG titers against each component; opsonophagocytic killing activity against pneumococcal strains from Clades 2, 3, and 4 from PspA Families 1 and 2; and neutralization antibody titers against pneumolysin post-vaccination. Conclusions: The recombinant protein-based pneumococcal vaccine exhibited a favorable safety profile and potent immunogenicity in animal models, indicating promise for broad protection against pneumococcal disease. These findings support the further development of PBPVs as a viable alternative to conventional polysaccharide-based vaccines.

Background: Streptococcus pneumoniae (Spn) is a leading bacterial pathogen responsible for severe invasive diseases, including meningitis, sepsis, and pneumonia. Current pneumococcal vaccines, which are all based on capsular polysaccharide antigens, provide limited protection and are further compromised by post-vaccination serotype replacement. Pneumococcal surface protein A (PspA), a highly conserved virulence factor expressed across diverse serotypes, has emerged as a promising candidate antigen for novel protein-based vaccines. However, progress in this field has been hindered by the absence of standardized in vitro functional antibody assays. Methods: This study established a robust functional antibody detection method for PspA-based protein vaccines by modifying the conventional multiplex opsonophagocytic killing assay (MOPA), originally designed for polysaccharide-based vaccines. Using polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) typing, a target strain panel was selected and developed to include representative strains from PspA Family 1-Clade 2 and Family 2-Clades 3 and 4. The MOPA protocol was optimized by extending the phagocytic reaction time to enhance sensitivity. Specificity was confirmed through recombinant PspA competitive inhibition assays. Results: The assay demonstrated high linearity (R² ≥ 0.98) between opsonophagocytic index (OI) and serum dilution, along with acceptable repeatability (CV ≤ 30%) and intermediate precision (CV ≤ 50%). Both preclinical and clinical serum samples exhibited potent bactericidal activity against diverse PspA families, independent of capsule type. Conclusions: This study provided a standardized framework to support the development and regulatory assessment of protein-based pneumococcal vaccines.

BackgroundPneumococcal disease (PD) remains a significant pediatric health burden. While current vaccines protect against most targeted serotypes, infections from non-vaccine serotypes persist, and timely completion of immunization schedules is not universal. The 15-valent pneumococcal conjugate vaccines (PCV), developed by LvZhu & Co. Ltd., covers all 13 serotypes in PCV13 (Prevnar 13™) and additional serotypes (2 and 12F). This pivotal Phase III trial systematically compares the safety and immunogenicity of PCV15 versus PCV13 (Prevnar 13™).Methods1,300 at 2 months of age randomized 1:1 to receive PCV15 or PCV13, and 650 at 3 months assigned to PCV15, all on a four-dose schedule. Safety was assessed as the proportion of participants with adverse events (AEs) after each dose. Immunogenicity was evaluated by serotype-specific anti-pneumococcal IgG levels, seropositivity rates, geometric mean concentrations (GMCs), opsonophagocytic activity (OPA), and geometric mean titers (GMTs) based on blood samples collected pre-dose 1, at 1-month post-dose 3 (PD3), pre-dose 4 and at 1-month post-dose 4 (PD4).Results Safety profiles, including AE and serious AE (SAEs) rates, were comparable across groups with no vaccine-related SAEs. For shared serotypes, IgG seropositivity and GMCs in both PCV15 age groups (2- and 3-month) were non-inferior to the PCV13 group. The new serotypes (2 and 12F) achieved >70% seropositivity and were non-inferior to the lowest PCV13 serotype (serotype 3). The 3-month PCV15 group was non-inferior to the 2-month PCV15 group for all serotypes. Assessment of OPA functional antibody responses indicates that antibodies induced by PCV15 possess bactericidal activity.Conclusions PCV15 demonstrated favorable safety in healthy infants. Its immunogenicity for the 13 shared serotypes was non-inferior to PCV13, and it also induced robust antibody responses against the two new serotypes (2 and 12F). These data support the inclusion of PCV15 in routine infant immunization programs for PD prevention.