Background: Protein-based pneumococcal vaccines (PBPVs) may offer expanded protection against Streptococcus pneumoniae and tackle the antimicrobial resistance crisis in pneumococcal infections. This study examined the safety and immunogenicity in healthy adults vaccinated with three doses of a protein-based pneumococcal vaccine containing pneumococcal surface protein A (PspA) (PRX1, P3296 and P5668) and in combination with a recombinant detoxified pneumolysin protein (PlyLD). Methods: This phase Ia randomized, double blind, placebo-controlled clinical study enrolled healthy adults aged 18–49 years. The participants were randomized into experimental (low-dose, medium-dose, high-dose) and placebo groups in a ratio of 3:1. Three doses of investigational vaccine were given to the participants with an interval of two months. Safety endpoints included the occurrence of total adverse reactions, solicited local and systemic adverse reactions, unsolicited adverse reactions, serious adverse events (SAEs), and several laboratory parameters. Immunogenicity endpoints included geometric mean titers (GMT) of anti-PspA (PRX1, P3296 and P5668) and anti-PlyLD antibodies level as determined by ELISA, seropositivity rates of PspA and PlyLD antibodies (>4-fold increase) and neutralization activity of anti-Ply antibody in serum. Results: A total of 118 participants completed the study of three doses. The candidate PBPV was safe and well-tolerated in all experimental groups. No vaccine-related SAEs were observed in this study. Most solicited adverse reactions were mild and transient. The most frequently reported solicited adverse reactions in the medium- and high-dose groups was pain at the injection site, while in the low-dose group it was elevated blood pressure. The immunogenicity data showed a sharp increase in the GMT level of anti-PspA-RX1, anti-PspA-3296, anti-PspA-5668, and anti-PlyLD antibodies in serum. The results also showed that the elicited antibodies were dosage-dependent. The high-dose group showed a higher immune response against PspA-RX1, PspA-3296, PspA-5668, and PlyLD antigens. However, repeat vaccination did not increase the level of anti-PspA antibodies but the level of anti-PlyLD antibody. High seropositivity rates were also observed for anti-PspA-RX1, anti-PspA-3296, anti-PspA-5668, and anti-PlyLD antibodies. In addition, a significant difference in the GMT levels of anti-Ply antibody between the high-, medium-, and low-dose groups post each vaccination were indicated by neutralization activity tests. Conclusions: The PBPV showed a safe and immunogenic profile in this clinical trial. Taking into consideration both safety and immunogenicity data, we propose a single dose of 50 µg (medium dose) of PBPV as the optimum approach in providing expanded protection against Streptococcus pneumoniae.

Objectives: This randomized, double-blind, active-controlled non-inferiority phase 4 clinical trial was conducted to evaluate the immunogenicity and safety of a 23-valent pneumococcal polysaccharide vaccine (PPSV23) compared to an active comparator vaccine. Methods: Pneumococcal vaccine-naïve participants aged ≥2 years were randomly assigned in a 2:1 ratio to receive a single dose of either the investigational vaccine (n = 1199) or the comparator vaccine (n = 600). Immunogenicity was evaluated at baseline and 30 days post-vaccination by measuring serotype-specific IgG antibodies against all 23 pneumococcal serotypes using enzyme-linked immunosorbent assay. The primary outcome was seroconversion, defined as a ≥two-fold increase in serotype-specific IgG antibody titers at day 30 compared to baseline. Results: At one month post-vaccination, seroconversion rates for each of the 23 serotypes ranged from 59.22% to 95.67% in the treatment group, compared to 59.66% to 94.07% in the control group. Non-inferiority was demonstrated for all serotypes, with the lower bounds of the 95% confidence intervals (95%CI) for rate differences exceeding the predefined −10% margin. Moreover, superiority was observed for 12 serotypes (6B, 23F, 1, 2, 4, 8, 9N, 9V, 11A, 15B, 17F and 18C), as the lower bounds of their 95%CI for rate differences were above 0. Adverse reactions were reported in 236 (19.68%) participants of the investigational group and 118 (19.67%) of the control group within 30 days post-vaccination, with no significant differences between groups. Conclusions: The PPSV23 vaccine administered among individual aged ≥2 years was safe, well tolerated and immunogenic, eliciting an immune response either comparable to or higher than control vaccine. These findings support its use as a safe and effective option for pneumococcal immunization.

Background/Objectives: The immunogenicity of Streptococcus pneumoniae vaccines is commonly evaluated by assessing the fold increase or proportions exceeding 0.35 μg/mL in serotype-specific IgG antibody levels post-vaccination. Establishing baseline antibody levels in unvaccinated populations is therefore essential for defining serological thresholds and understanding naturally acquired immunity. This study aimed to assess the seroprevalence and baseline levels of IgG antibodies specific to 13 pneumococcal capsular polysaccharide serotypes in healthy infants and young children across multiple regions of China from 2016 to 2023, supporting evidence-based PCV13 vaccination strategies. Methods: IgG concentrations for 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were measured in unvaccinated individuals using the WHO-recommended ELISA. Univariate and multivariate analyses were applied to evaluate regional, age, and gender effects on baseline antibody levels. Results: GMCs for serotypes 6B, 14, 19A, and 19F exceeded 0.35 μg/mL, with 14 being the highest (1.64 μg/mL) and serotypes 3 and 4 the lowest. Significant regional variation (p < 0.001) and a U-shaped age trend were observed, with the lowest being at 7–11 months (p = 0.003). Conclusions: Baseline IgG levels varied by region and age. No significant gender differences were observed, and overall antibody levels were higher in the southern region.