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.

Background: Influenza is a serious contagious disease caused by influenza virus. It is particularly dangerous for children, potentially leading to severe and even fatal complications. The aim of this study was to evaluate the safety and immunogenicity of two candidate quadrivalent influenza subunit vaccines in children aged 6–35 months. Methods: The subjects were randomly divided into three groups at a 1:1:1 ratio and received the corresponding vaccines: QIV-Sub-HD (Quadrivalent Influenza Subunit Vaccine, High Dose), QIV-Sub-LD (Quadrivalent Influenza Subunit Vaccine, Low Dose) and QIV-Split-LD (Quadrivalent Influenza Split-Virion Vaccine, Low Dose). Adverse events were recorded at 30 min, 0–7 days and 8–28 and 30 days after each dose of immunization. Serious adverse events (SAEs) were collected and reported within 6 months after the full vaccination. Blood samples were collected before the first dose and on 28 days, 3 months and 6 months after full vaccination for antibody detection to evaluate the immunogenicity and duration of immune responses. Results: The results showed that the relative and absolute criteria met the goals set by the clinical trial protocol, indicating that both vaccines are immunogenic. From the first dose to 30 days after full vaccination, the total incidence of adverse reactions in the QIV-Sub-HD, QIV-Sub-LD and QIV-Split-LD groups was 29.64%, 33.33% and 29.64%, respectively. The main symptoms were fever, cough, diarrhea and vomiting. No new safety concerns were identified. Conclusions: The quadrivalent influenza subunit vaccines candidate, manufactured by Ab&B Bio-tech Co., Ltd. JS., are safe and immunogenic in children aged 6–35 months.

Background: In recent years, breakthrough varicella cases among individuals who have received a single dose of varicella vaccine (VarV) have increased notably, suggesting that the long-term protection following a one-dose VarV regimen requires further investigation. This study aims to evaluate the immune persistence following a single dose of Sinovac VarV at 5 and 8 years post-vaccination. Methods: In this Phase 4, open-label, observational follow-up study, participants aged 1 to 12 years (referring to the age of vaccination) who had received a single dose of either Sinovac VarV or placebo in the previous phase 3 trial were enrolled in a 1:1 ratio. Blood samples were collected 5 years and 8 years post-vaccination to measure antibody levels against varicella using the fluorescent antibody to membrane antigen (FAMA) method. A total of 487 and 422 participants were included in the 5-year and 8-year immune persistence analyses, respectively. The endpoints comprised the seropositive rates (≥1:4 and ≥1:8) and the geometric mean titers (GMTs) of varicella antibodies at both 5 and 8 years following vaccination. Results: Varicella antibody levels declined from 30 days post vaccination but remained stable from 5 to 8 years. Five years after vaccination, the seropositive rates (≥1:4) of varicella antibody were 100% in the VarV group and 80.83% in the placebo group; for ≥1:8, the rates were 89.07% and 64.17%, respectively. The corresponding GMTs were 1:13.67 and 1:7.71, respectively. Eight years after vaccination, the seropositive rates (≥1:4) were 99.54% in the VarV group and 90.69% in the placebo group; for ≥1:8, they were 88.53% and 74.51%, with GMTs of 1:13.52 and 1:9.91, respectively. Eight years post-vaccination, the seropositive rates and antibody levels in the VarV group remained nearly the same as by 5 years. Conclusions: Sinovac VarV can confer good immune persistence for up to 8 years following a single dose of vaccination in children aged 1 to 12 years. However, given the declining trend in antibody levels over time, revaccination may be needed to maintain protective immunity.

Background: The multidose Sabin-strain inactivated poliovirus vaccine (sIPV) has the potential to significantly aid in the eradication of poliomyelitis, particularly in low- and middle-income countries. As part of a phase III clinical trial in which infants were given three doses of primary immunization at 2, 3, and 4 months of age, this study aimed to evaluate immune persistence following primary immunization, as well as the safety and immunogenicity of a booster of the 5-dose sIPV in infants aged 18 months. Methods: Infants aged 18 months were given one booster dose of 5-dose sIPV in stage one, which was open-label. Unblinding was performed for stage two after completing primary immunization, which was randomized, blinded, and controlled; infants aged 18 months in the test group I–III, IPV group, and single-dose sIPV group were given one booster dose of 5-dose sIPV, conventional IPV, and single-dose sIPV, respectively, in stage two. Results: This study included 1438 infants in the immune persistence and safety set and 1387 infants in the booster per-protocol set. Fourteen months after primary immunization, the seropositivity rates (≥1:8) for types 1–3 were 100%, 99.88%, and 99.53% in the 5-dose sIPV groups; 100%, 98.97%, and 97.23% in the IPV group; and 99.66%, 100%, and 99.66% in the single-dose sIPV group. A total of 30 days after booster immunization, the seropositivity rates (≥1:8) of 3 serotypes in all the groups reached 100%. The geometric mean titers of neutralizing antibodies for types 1–3 in the 5-dose sIPV group were 9962.89, 10273, and 7870.21, with geometric mean increases of 15.76, 33.15, and 24.5, compared to the pre-booster level. The overall incidence of adverse reactions was 8.97%, with fever being the most common, observed at rates of 7.1%, 5.52%, and 7.96% in the 5-dose sIPV, IPV, and single-dose groups, respectively (p = 0.4845). Conclusions: The 5-dose sIPV has shown promising immune persistence and robust immune response following a booster immunization, coupled with an acceptable safety profile.

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.