The lncRNA FENDRR inhibits colorectal cancer progression via interacting with and triggering GSTP1 ubiquitination by FBX8.

Background: Colorectal cancer (CRC) is characterized by its aggressiveness and high fatality rate. Long noncoding RNAs (lncRNAs) as molecular scaffolding in CRC have received little attention. Methods: The TCGA database was used to find putative anti-oncogenic lncRNAs in CRC. The effect of FENDRR on CRC was evaluated using the colony formation assay, transwell assays, and wound healing assays, and FENDRR expression was validated by qRT-PCR. The location of the FENDRR binding proteins was determined by an RNA pull-down experiment, and the retrieved proteins were recognized by mass spectrometry. RNA immunoprecipitation (RIP) studies were used to demonstrate the interaction of GSTP1, FBX8, and FENDRR. Co-IP and immunofluorescence were utilized to confirm the connection between GSTP1 and FBX8. To determine the precise signaling pathways implicated in the action of FENDRR in CRC, we performed next-generation sequencing (NGS) on CRC cells transfected with a vector overexpressing FENDRR. Results: The expression of FENDRR was significantly downregulated in CRC tissue and cells. The results of the function experiments showed that overexpression of FENDRR reduced CRC cells' ability to proliferation, invasion, migration and tube formation. In terms of mechanism, FENDRR could bind both GSTP1 and FBX8, act as a molecular scaffold, and utilize FBX8 to regulate the stability of GSTP1's protein. Additionally, the outcomes of NGS and qRT-PCR demonstrated that the expression of genes linked to the HIF-1 pathway was down-regulated following FENDRR overexpression. Lastly, rescue tests demonstrated that overexpression of GSTP1 in CRC cells could completely restore the inhibition induced by FENDRR. Conclusion: In this study, we found that the molecular scaffolding protein FENDRR regulates the ubiquitination of GSTP1 and the suppression of the HIF-1 signaling pathway in the development of CRC. Our research provides more evidence of FENDRR's crucial role in the emergence of CRC and identifies it as a potential therapeutic target for CRC patients.

Immunogenicity and safety of an Escherichia coli-produced human papillomavirus (types 6/11/16/18/31/33/45/52/58) L1 virus-like-particle vaccine: a phase 2 double-blind, randomized, controlled trial.

The Escherichia coli-produced human papillomavirus (HPV) 16/18 bivalent vaccine (Cecolin) has received prequalification by the World Health Organization based on its high efficacy and good safety profile. We aimed to evaluate the immunogenicity and safety of the second-generation nonavalent HPV 6/11/16/18/31/33/45/52/58 vaccine (Cecolin 9) through the randomized, blinded phase 2 clinical trial. Eligible healthy women aged 18-45 years were randomly (1:1) allocated to receive three doses of 1.0 mL (270 µg) of Cecolin 9 or placebo with a 0-1-6-month schedule. The primary endpoint was the seroconversion rate and geometric mean titer of neutralizing antibodies (nAbs) one month after the full vaccination course (month 7). The secondary endpoint was the safety profile including solicited adverse reactions occurring within 7 d, adverse events (AEs) occurring within 30 d after each dose, and serious adverse events (SAEs) occurring during the 7-month follow-up period. In total, 627 volunteers were enrolled and randomly assigned to Cecolin 9 (n = 313) or placebo (n = 314) group in Jiangsu Province, China. Almost all participants in the per-protocol set for immunogenicity (PPS-I) seroconverted for nAbs against all the nine HPV types at month 7, while two failed to seroconvert for HPV 11 and one did not seroconvert for HPV 52. The incidence rates of total AEs in the Cecolin 9 and placebo groups were 80.8% and 72.9%, respectively, with the majority of them being mild and recovering shortly. None of the SAEs were considered related to vaccination. In conclusion, the E. coli-produced 9-valent HPV (9vHPV) vaccine candidate was well tolerated and immunogenic, which warrants further efficacy studies in larger populations.

A randomized, open-label, phase 3 study evaluating safety and immunogenicity of 13-valent pneumococcal conjugate vaccine in Chinese infants and children under 6 years of age.

Streptococcus pneumoniae causes a considerable disease burden among children in China. Many isolates exhibit antimicrobial resistance but are often serotypes covered by the 13-valent pneumococcal conjugate vaccine (PCV13). Because the approved infant immunization schedule in China allows PCV13 vaccination only for those 6 weeks to 15 months of age, this phase 3 study was conducted to evaluate PCV13 immunogenicity and safety in unvaccinated older infants and children. Eligible participants were stratified by age into four cohorts: Cohort 1 (n = 125), 6 weeks-2 months; Cohort 2 (n = 354), 7-<12 months; Cohort 3 (n = 250), 1 -<2 years; Cohort 4 (n = 207), 2-<6 years. Cohort 1 received PCV13 at ages 2, 4, and 6 months; older cohorts were randomized 2:1 to PCV13 or Haemophilus influenzae type b (Hib) vaccine using age-appropriate schedules. Within-group immune responses were assessed by immunoglobulin G (IgG) concentrations and opsonophagocytic activity (OPA) titers. Safety evaluations included solicited reactogenicity events and adverse events (AEs). IgG geometric mean concentrations and OPA geometric mean titers for all 13 PCV13 serotypes increased for all participants vaccinated with PCV13, but not those vaccinated with Hib. Immune responses in Cohorts 2-4 were generally comparable with those in Cohort 1 (the infant series) for most serotypes. PCV13 was well tolerated across cohorts, with reported AEs consistent with expectations in these age groups; no new safety signals were identified. These results suggest that PCV13 administered as a catch-up regimen to infants and children 7 months-<6 years of age in China will effectively reduce vaccine-type pneumococcal disease in this population. NCT03574389.

Safety and immunogenicity of an Escherichia coli-produced 9-valent human papillomavirus L1 virus-like particle vaccine (types 6/11/16/18/31/33/45/52/58) in healthy adults: an open-label, dose-escalation phase 1 clinical trial.

Background: A safe and highly efficacious Escherichia coli (E. coli)-produced HPV 16/18 bivalent vaccine has been prequalified by the World Health Organization. Here, we conducted a single-center, open-label, dose-escalation phase 1 clinical trial to evaluate the safety and immunogenicity of the second-generation nonavalent HPV 6/11/16/18/31/33/45/52/58 vaccine. Method: Twenty-four eligible volunteers aged 18-45 years were enrolled in January 2019 in Dongtai, China and received 0.5 mL (135 µg) or 1.0 mL (270 µg) of the candidate vaccine with a 0/1/6-month dose-escalation schedule. Local and systemic adverse events (AEs) occurring within 30 days after each vaccination and serious adverse events (SAEs) occurring within 7 months were recorded. Blood samples from each participant were collected before and 2 days after the first and third vaccinations to determine changes in laboratory parameters. Serum IgG and neutralizing antibody (nAb) levels against each HPV type at month 7 were analyzed (ClinicalTrials.gov: NCT03813940). Findings: The incidences of total AEs in the 135 µg and 270 µg groups were 66.7% and 83.3%, respectively. All AEs were mild or moderate, and no SAEs were reported. No clinically significant changes were found in paired blood indices before or after any of the vaccinations. All the participants in the per-protocol set except for two who failed to seroconvert for HPV 11 or 58 in the 135 µg group seroconverted at month 7 for both IgG and nAbs. Interpretation: The candidate E. coli-produced 9vHPV vaccine has been preliminarily proven to be well tolerated and immunogenic, which encourages further studies in large cohorts with a wider age range. Funding: This study was supported by the National Natural Science Foundation of China, Fujian Provincial Natural Science Foundation, Fujian Province Health and Education Joint Research Program, Xiamen Science and Technology Plan Project, Fundamental Research Funds for the Central Universities, CAMS Innovation Fund for Medical Sciences of China, and Xiamen Innovax Biotechnology Co., Ltd.

Safety of AS04-HPV-16/18 vaccine in Chinese women aged 26 years and older and long-term protective effect in women vaccinated at age 18-25 years: A 10-year follow-up study.

INTRODUCTION: The pivotal efficacy study assessed efficacy and safety of GSK's AS04-HPV-16/18 vaccine in Chinese women aged 18-25 years up to 6 years. The present extension study, performed 4 years later, offered AS04-HPV-16/18 vaccination to placebo recipients. Vaccine safety and its long-term protective effect were assessed at Year 10. METHODS: All 6051 women who received AS04-HPV-16/18 or the placebo during the initial study (NCT00779766) were invited to phase III/IV, open-label, partially controlled extension Year 10 study (NCT03629886). Placebo recipients were offered three-dose AS04-HPV-16/18 vaccination and followed up over 12 months to assess the safety. Cervical samples from all women were examined. Vaccine efficacy (VE) against incident infections and cytological lesions associated with HPV-16/18 and other oncogenic types was assessed as exploratory objective. RESULTS: Among 3537 women (out of 6051) enrolled in the extension study, 1791 women (mean age 32.7 years; standard deviation 1.8 years) received AS04-HPV-16/18 and reported no serious adverse events, potential immune-mediated diseases, or adverse pregnancy outcomes related to vaccination. Among 6051 women, VE against incident HPV-16, -18, and -16/18 infections up to Year 10 was 82.8% (95% confidence interval: 72.5-89.7), 79.8% (64.5-89.2), and 80.8% (72.4-87.0), respectively. VE against HPV-16/18 ASC-US+, CIN1+, and CIN2+ was 92.7% (82.2-97.7), 94.8% (67.4-99.9), and 90.5% (34.6-99.8), respectively. CONCLUSION: AS04-HPV-16/18 vaccine showed an acceptable safety profile in Chinese women vaccinated at age 26 years or above, and a long-term protection similar to other efficacy trials worldwide.

Efficacy, safety, and immunogenicity of an Escherichia coli-produced Human Papillomavirus (16 and 18) L1 virus-like-particle vaccine: end-of-study analysis of a phase 3, double-blind, randomised, controlled trial.

BACKGROUND: This Escherichia coli-produced bivalent HPV 16 and 18 vaccine was well tolerated and effective against HPV 16 and 18 associated high-grade genital lesions and persistent infection in interim analysis of this phase 3 trial. We now report data on long-term efficacy and safety after 66 months of follow-up. METHODS: This phase 3, double-blind, randomised, controlled trial was done in five study sites in China. Eligible participants were women aged 18-45 years, with intact cervix and 1-4 lifetime sexual partners. Women who were pregnant or breastfeeding, had chronic disease or immunodeficiency, or had HPV vaccination history were excluded. Women were stratified by age (18-26 and 27-45 years) and randomly (1:1) allocated by software (block randomisation with 12 codes to a block) to receive three doses of the E coli-produced HPV 16 and 18 vaccine or hepatitis E vaccine (control) and followed-up for 66 months. The primary outcomes were high-grade genital lesions and persistent infection (longer than 6 months) associated with HPV 16 or 18 in the per-protocol susceptible population. This trial was registered with ClinicalTrials.gov, NCT01735006. FINDINGS: Between Nov 22, 2012, and April 1, 2013, 8827 women were assessed for eligibility. 1455 women were excluded, and 7372 women were enrolled and randomly assigned to receive the HPV vaccine (n=3689) or control (n=3683). Vaccine efficacy was 100·0% (95% CI 67·2-100·0) against high-grade genital lesions (0 [0%] of 3310 participants in the vaccine group and 13 [0·4%] of 3302 participants in the control group) and 97·3% (89·9-99·7) against persistent infection (2 [0·1%] of 3262 participants in the vaccine group and 73 [2·2%] of 3271 participants in the control group) in the per-protocol population. Serious adverse events occurred at a similar rate between vaccine (267 [7·2%] of 3691 participants) and control groups (290 [7·9%] of 3681); none were considered related to vaccination. INTERPRETATION: The E coli-produced HPV 16 and 18 vaccine was well tolerated and highly efficacious against HPV 16 and 18 associated high-grade genital lesions and persistent infection and would supplement the global HPV vaccine availability and accessibility for cervical cancer prevention. FUNDING: National Natural Science Foundation of China, National Key R&D Program of China, Fujian Provincial Project, Fundamental Funds for the Central Universities, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, and Xiamen Innovax.

Comparison of HPV neutralizing and IgG antibodies in unvaccinated female adolescents.

Aims: To analyze the consistency between HPV-neutralizing antibodies and specific total IgG antibodies in unvaccinated females. Materials & methods: Serum samples from 978 unvaccinated Chinese females aged 9-26 years were measured for antibodies against HPV-16 and HPV-18 using simultaneous pseudovirus-based neutralization assay and ELISA. Results: There was a moderate level of consistency between HPV-neutralizing antibodies and specific IgG in females aged 18-26 years (Cohen's κ coefficient for HPV-16 and HPV-18: 0.52 and 0.38) and poor consistency in those aged 9-17 years (Cohen's κ coefficient <0.05). However, Cohen's κ coefficient remained almost unchanged in sensitivity analysis when the IgG antibody cutoff value was raised. Conclusion: HPV-neutralizing antibodies are a more specific indicator for the evaluation of HPV natural humoral immunity.

Safety and immunogenicity of a live-attenuated influenza virus vector-based intranasal SARS-CoV-2 vaccine in adults: randomised, double-blind, placebo-controlled, phase 1 and 2 trials.

BACKGROUND: All currently available SARS-CoV-2 vaccines are administered by intramuscular injection. We aimed to evaluate the safety and immunogenicity of a live-attenuated influenza virus vector-based SARS-CoV-2 vaccine (dNS1-RBD) administered by intranasal spray in healthy adults. METHODS: We did double-blind, randomised, placebo-controlled phase 1 and 2 trials, followed by a phase 2 extension trial, at a single centre in Jiangsu, China. Healthy adults (≥18 years) who had negative serum or fingertip blood total antibody tests for SARS-CoV-2 (in phases 1 and 2), with no prevalent SARS-CoV-2 infection or history of infection and no SARS-CoV-2 vaccination history (in all three trials reported here), were enrolled. Participants were randomly allocated (4:1 in phase 1, 2:1 in phase 2, and 1:1 in the extension trial) to receive two intranasal doses of the dNS1-RBD vaccine or placebo on days 0 and 14 or, for half of the participants in phase 2, on days 0 and 21. To avoid cross-contamination during administration, vaccine and placebo recipients were vaccinated in separate rooms in the extension trial. The phase 1 primary outcome was safety (adverse events recorded on days 0-44; serious adverse events recorded from day 0 until 12 months after the second dose). In the phase 2 and extension trials, the primary immunogenicity outcomes were SARS-CoV-2-specific T-cell response in peripheral blood (measured by IFN-γ ELISpot), proportion of participants with positive conversion for SARS-CoV-2 receptor-binding domain (RBD)-specific IgG and secretory IgA (s-IgA) antibodies, and concentration of SARS-CoV-2 RBD IgG in serum and SARS-CoV-2 RBD s-IgA in the nasopharynx (measured by ELISA) at 1 month after the second dose in the per-protocol set for immunogenicity. χ2 test and Fisher's exact test were used to analyse categorical data, and t test and Wilcoxon rank sum test to compare the measurement data between groups. These trials were registered with the Chinese Clinical Trial Registry (ChiCTR2000037782, ChiCTR2000039715, and ChiCTR2100048316). FINDINGS: Between Sept 1, 2020, and July 4, 2021, 63, 724, and 297 participants without a history of SARS-CoV-2 vaccination were enrolled in the phase 1, phase 2, and extension trials, respectively. At least one adverse reaction after vaccination was reported in 133 (19%) of 684 participants in the vaccine groups. Most adverse reactions were mild. No vaccine-related serious adverse event was noted. Specific T-cell immune responses were observed in 211 (46% [95% CI 42-51]) of 455 vaccine recipients in the phase 2 trial, and in 48 (40% [31-49]) of 120 vaccine recipients compared with one (1% [0-5]) of 111 placebo recipients (p<0·0001) in the extension trial. Seroconversion for RBD-specific IgG was observed in 48 (10% [95% CI 8-13]) of 466 vaccine recipients in the phase 2 trial (geometric mean titre [GMT] 3·8 [95% CI 3·4-4·3] in responders), and in 31 (22% [15-29]) of 143 vaccine recipients (GMT 4·4 [3·3-5·8]) and zero (0% [0-2]) of 147 placebo recipients (p<0·0001) in the extension trial. 57 (12% [95% CI 9-16]) of 466 vaccine recipients had positive conversion for RBD-specific s-IgA (GMT 3·8 [95% CI 3·5-4·1] in responders) in the phase 2 trial, as did 18 (13% [8-19]) of 143 vaccine recipients (GMT 5·2 [4·0-6·8]) and zero (0% [0-2]) of 147 placebo recipients (p<0·0001) in the extension trial. INTERPRETATION: dNS1-RBD was well tolerated in adults. Weak T-cell immunity in peripheral blood, as well as weak humoral and mucosal immune responses against SARS-CoV-2, were detected in vaccine recipients. Further studies are warranted to verify the safety and efficacy of intranasal vaccines as a potential supplement to current intramuscular SARS-CoV-2 vaccine pools. Steps should be taken in future studies to reduce the potential for cross-contamination caused by the vaccine strain aerosol during administration. FUNDING: National Key Research and Development Program of China, National Science, Fujian Provincial Science, CAMS Innovation Fund for Medical Sciences, and Beijing Wantai Biological Pharmacy Enterprise.

Long-Term immunopersistence and safety of the Escherichia coli-produced HPV-16/18 bivalent vaccine in Chinese adolescent girls.

The study assessed long-term immunopersistence and safety of the Escherichia coli (E. coli)-produced HPV-16/18 bivalent vaccine. In total, 979 participants in the initial immunogenicity noninferiority study, including girls aged 9-14 years who were randomized in a 1:1 ratio to receive 2 doses at months 0 and 6 (n = 301) or 3 doses at months 0, 1 and 6 (n = 304); girls aged 15-17 years (n = 149) and women aged 18-26 years (n = 225) who received 3 doses of the vaccine, were invited to participate in follow-up to 30 months post vaccination (NCT03206255). Serum samples were collected at months 18 and 30, and anti-HPV-16/18 IgG antibodies were measured by enzyme-linked immunosorbent assay. Serious adverse events (SAEs) occurred from month 7 through month 30 were recorded. At month 30, in the per-protocol set, all participants remained seropositive, except for one girl in the 9-14 years (2 doses) group who seroconverted to negative for HPV-18. HPV-16 and HPV-18 antibody levels were higher in girls aged 9-17 years who received 3 doses (125.3 and 60.2 IU/ml) than in women aged 18-26 years who received 3 doses (72.6 and 28.3 IU/ml), and those in girls aged 9-14 years who received 2 doses (73.2 and 24.9 IU/ml) were comparable to those in women aged 18-26 years who received 3 doses. No SAEs were reported to be causally related to vaccination. The E. coli-produced bivalent HPV-16/18 vaccine is safe and induces persistent protective antibodies for up to 30 months after vaccination in girls aged 9-17 years receiving 2 or 3 doses.

Evaluation of a recombinant five-antigen Staphylococcus aureus vaccine: The randomized, single-centre phase 1a/1b clinical trials.

BACKGROUND: Staphylococcus aureus is an important pathogen that causes hospital and community infections. To control Staphylococcus aureus infection and reduce the usage of antibiotics, we evaluated the safety and immunogenicity of a recombinant five-antigen Staphylococcus aureus vaccine (rFSAV) in healthy adults. METHODS: We conducted a randomized, double-blind, placebo-controlled phase 1a study and a randomized, open-label phase 1b study. In phase 1a, we randomly allocated 144 healthy participants in a ratio of 1:1:1:1 to receive the low-(60 µg), middle-(120 µg), and high-dose (240 µg) vaccine or placebo at day 0, 3, 7 and 14. In phase 1b, 144 healthy participants were randomly allocated at a ratio of 1:1:1:1 to receive 0-3-7, 0/0-7, 0/0-3-7, 0/0-7-14 regimens to estimate the optimal strategy. The primary study endpoint was the incidence of solicited adverse events post-vaccination. The immunogenicity endpoints included the level of specific antibodies to five antigens after vaccination, as well as the cellular immune responses and functional antibodies. RESULTS: There were 31 (86%), 30 (83%), and 32 (89%) of 36 participants in the low-, middle-, and high-dose group reported solicited adverse events, respectively, most of the adverse events were mild or moderate. In phase 1b, the dose-adjusted rFSAV (90 µg) showed a better safety profile in the four immune procedures, and no vaccine-related serious adverse events were reported. The antigen-specific binding antibodies started to increase at day 7 and reached the peak around day 14 to 21. The cellular immune responses and functional antibodies also were substantially above background levels. CONCLUSIONS: rFSAV is safe, well tolerated in healthy adults, elicits rapid and robust specific humoral and cellular immune responses with unconventional immunization procedure in phase 1a and 1b. It deserves to be noted and further explored. CLINICAL TRIALS REGISTRATION: NCT02804711 and NCT03966040.

Immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine administered in a prime-boost regimen among Chinese infants: a randomized, double blind phase III clinical trial.

This study aimed to evaluate the immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine (PCV13). In total, 1200 infants were randomized into two groups with a 1:1 allocation and received a three-dose series of tested PCV13 or control PCV13 at ages 2, 4 and 6 months, respectively, and a booster dose at 12-15 months. Blood samples were collected before and 30 days after primary and booster vaccination. Serotype-specific antibodies were measured using ELISA for immunoglobulin G (IgG) and OPA for functional antibodies. Safety data were collected for 30 days after each inoculation. Results showed that post primary vaccination seropositive rates of all 13 serotypes except type 3 were not significantly different between two groups. The seropositive rate for type 3 in Group T was significantly higher than Group C (P < .0001). For all 13 serotypes except type 7 F, the GMCs in Group T were significantly higher than Group C. The GMC for type 7 F in Group T (P < .0009) was significantly lower than Group C. The frequencies of overall adverse events (P = .0064) and solicited adverse reactions (P = .0019) in Group T were significantly lower than Group C. Post booster vaccination, seropositive rates for all serotypes in Group T were 100.00%. For all serotypes except type 23 F, IgG GMCs in Group T were significantly higher than Group C. Totally, 21 subjects reported SAEs and all but one were considered irrelevant or probably irrelevant to vaccination. In conclusion, the tested PCV13 showed non-inferior immunogenicity and had a good safety profile compared with control vaccine.

Naturally acquired HPV antibodies against subsequent homotypic infection: A large-scale prospective cohort study.

BACKGROUND: Although recent studies have suggested that naturally acquired Human papillomavirus (HPV) antibodies are partly protective against subsequent homotypic infection, the extent of protection remains indecisive. Here, we evaluate the protective effect of neutralizing and IgG antibodies simultaneously. METHODS: In a cohort of 3634 women aged 18-45 years from the control arm of a phase III trial of the HPV-16/18 bivalent vaccine, participants were tested for neutralizing antibodies by pseudovirion-based neutralization assay (PBNA) and IgG antibodies by enzyme-linked immunosorbent assay (ELISA) at baseline. HPV-16/18 incident and persistent infections were identified using cervical specimens periodically collected during the 5·5 years of follow-up. The protective effects of HPV-16/18 neutralizing and IgG antibodies against homotypic infection were assessed using a Cox proportional hazard model. FINDINGS: For the persistent infection (PI) endpoints of HPV-16/18 lasting for over 6/12 months, a prevalence of type-specific neutralizing antibodies was highly protective (6-month PI: hazard ratio (HR) = 0·16, 95% confidence interval (CI): 0·04, 0·65; 12-month PI: HR = 0·23, 95% CI: 0·06, 0·94), whereas a prevalence of IgG antibodies was associated with minor and non-significant protection (6-month PI: HR = 0·66, 95% CI: 0·40, 1·09; 12-month PI: HR = 0·66, 95% CI: 0·36, 1·20). After increasing the cut-off value to the median IgG level, the risk of 6-month PI was significantly lower in seropositive vs seronegative women (HR = 0·38, 95% CI: 0·18, 0·83). INTERPRETATION: Naturally acquired antibodies are associated with a substantially reduced risk of subsequent homotypic infection. FUNDING: NSFC; The Fujian Province Health Education Joint Research Project; Xiamen Science and Technology Major Project; CIFMS; and Xiamen Innovax.

Cross-neutralization Capacity of Immune Serum from Different Dosage of Sabin Inactivated Poliovirus Vaccine Immunization against Multiple Individual Polioviruses.

Introduction: Sabin strain inactivated poliovirus vaccine (sIPV) developed by Sinovac Biotech Co., Ltd., has shown good safety and immunogenicity against parental strains among infants in several finished pre-licensure clinical trials.Areas covered: To further study the neutralizing capacity of investigational sIPV immune serum against Sabin, Salk and recently circulating poliovirus strains, neutralization assay against ten individual strains was performed on backup serum collected from 250 infant participants of the finished phase II clinical trial.Expert commentary:: The sIPV can generate good immunogenicity against Sabin, Salk and recently circulating poliovirus strains. Taking into account its lower containment requirements and financial costs compared with the conventional Salk strain inactivated poliovirus vaccine, sIPV is an affordable and practical option for polio eradication.

Inflammation-related adverse reactions following vaccination potentially indicate a stronger immune response.

Concerns about vaccine safety are an important reason for vaccine hesitancy, however, limited information is available on whether common adverse reactions following vaccination affect the immune response. Data from three clinical trials of recombinant vaccines were used in this post hoc analysis to assess the correlation between inflammation-related solicited adverse reactions (ISARs, including local pain, redness, swelling or induration and systematic fever) and immune responses after vaccination. In the phase III trial of the bivalent HPV-16/18 vaccine (Cecolin®), the geometric mean concentrations (GMCs) for IgG anti-HPV-16 and -18 (P<0.001) were significantly higher in participants with any ISAR following vaccination than in those without an ISAR. Local pain, induration, swelling and systemic fever were significantly correlated with higher GMCs for IgG anti-HPV-16 and/or anti-HPV-18, respectively. Furthermore, the analyses of the immunogenicity bridging study of Cecolin® and the phase III trial of a hepatitis E vaccine yielded similar results. Based on these results, we built a scoring model to quantify the inflammation reactions and found that the high score of ISAR indicates the strong vaccine-induced antibody level. In conclusion, this study suggests inflammation-related adverse reactions following vaccination potentially indicate a stronger immune response.

Quadrivalent influenza vaccine (Sinovac Biotech) for seasonal influenza prophylaxis.

INTRODUCTION: Quadrivalent Influenza Vaccine (Sinovac Biotech) is a quadrivalent split-virion-inactivated influenza vaccine approved in China in June 2020 for individuals ≥3 years of age. It contains 15 µg hemagglutinin per strain including A/H1N1, A/H3N2, B/Victoria, and B/Yamagata, which could potentially improve protection against influenza B viruses. AREAS COVERED: In this review, we summarize the development of quadrivalent influenza vaccines in China and foreign countries, and assess the immunogenicity and safety from the phase I and III clinical trials of Quadrivalent Influenza Vaccine in individuals ≥3 years of age. We also discuss the potential application of Quadrivalent Influenza Vaccine in young children 6-35 months of age according to the results of the phase III trial. EXPERT COMMENTARY: The immunogenicity and safety profiles of Quadrivalent Influenza Vaccine containing two A and two B strains were comparable to the trivalent vaccines for the shared strains. The addition of a second B strain to the trivalent vaccine could induce superior immune responses for the alternate B strain. Since the two B strains co-circulated worldwide, the introduction of quadrivalent influenza vaccines has been expected to be a cost-effective strategy.

Safety and immunogenicity of meningococcal (Groups A and C) polysaccharide vaccine in children 2 to 6 y of age in China: a randomized, active-controlled, non-inferiority study.

Meningococcal serogroups A and C cause significant numbers of cases in China. The Sanofi Pasteur meningococcal polysaccharide A + C vaccine (Men-AC) was licensed in China in 1995. Immunogenicity and safety of a single dose of Men-AC against a similar marketed vaccine, the Lanzhou Institute serogroups A and C vaccine (Lanzhou-AC), were evaluated in children 2 to 6 y of age. Antibody titers were determined before and on Day 30 after vaccination using a serum bactericidal assay using baby rabbit complement (SBA-BR). Immunogenicity endpoints included rates of seroconversion (postvaccination antibody titers ≥4-fold higher) and seroprotection (postvaccination titers ≥1:8). Unsolicited systemic adverse events (AEs) within 30 minutes after vaccination, solicited injection site and systemic reactions between Days 0 and 7, unsolicited non-serious AEs within 30 d, and serious adverse events (SAEs) throughout were recorded. Seroconversion rates against serogroups A and C were 97.0% (95% confidence interval [CI], 94.5-98.6) and 94.7% (95% CI, 91.6-97.0), respectively, in the Men-AC group and 97.7% (95% CI, 95.4-99.1) and 94.8% (95% CI, 91.7-97.0), respectively, in the Lanzhou-AC group, while seroprotection rates were 98.0% (95% CI, 95.8-99.3) and 97.0% (95% CI, 94.5-98.6), respectively, in the Men-AC group and 99.0% (95% CI, 97.2-99.8) and 96.8% (95% CI, 94.1-98.4), respectively, in the Lanzhou-AC group. Non-inferiority of Men-AC with regard to immunogenicity was demonstrated since the lower bounds of the 95% CIs of the differences in rates between the two groups were > -5% for both serogroups. Both vaccines were well tolerated.

Efficacy of the AS04-adjuvanted HPV-16/18 vaccine in young Chinese women with oncogenic HPV infection at baseline: post-hoc analysis of a randomized controlled trial.

Human papillomavirus (HPV) vaccines are efficacious against HPV infections and associated lesions in women HPV-naïve at vaccination. However, vaccine efficacy (VE) against oncogenic, high-risk HPV (HR-HPV) types in women infected with any other HR-HPV type at first vaccination (baseline) remains unclear. This post-hoc analysis of a phase II/III study (NCT00779766) evaluated AS04-adjuvanted HPV-16/18 (AS04-HPV-16/18) VE against HR-HPV type infection in 871 Chinese women aged 18-25 years over a 72-month follow-up period. Study participants were DNA-negative at baseline to HR-HPV type(s) considered for VE and DNA-positive to any other HR-HPV type. Initial serostatus was not considered. Baseline DNA prevalence was 14.6% for any HR-HPV type and 10.6% excluding HPV-16/18. In the total vaccinated cohort for efficacy, VE against 6-month and 12-month HPV-16/18 persistent infections (PIs) in women DNA-negative to HPV-16/18 but DNA-positive to any other HR-HPV type at baseline was 100.0% (95% Confidence Interval [CI]: 79.8-100.0) and 100.0% (95%CI: 47.2-100.0), respectively. VE against HPV-16/18 incident infections in women DNA-positive to one vaccine type but DNA-negative to the other one at baseline was 66.8% (95%CI: -18.9-92.5). VE against HPV-31/33/45 incident infections, in women DNA-positive to HPV-16/18 and DNA-negative to the considered HPV type at baseline was 71.0% (95%CI: 27.3-89.8). No HPV-16/18 PIs were observed in vaccinated women with non-vaccine HPV A7/A9 species cervical infection at baseline. These findings indicated that women with existing HR-HPV infection at vaccination might still benefit from the AS04-HPV-16/18 vaccine. However, this potential benefit needs further demonstration in the future.

TGF-ß1-regulated miR-3691-3p targets E2F3 and PRDM1 to inhibit prostate cancer progression.

Transforming growth factor-ß1 (TGF-ß1) acts as a tumor promoter in advanced prostate cancer (PCa). We speculated that microRNAs (miRNAs) that are inhibited by TGF-ß1 might exert anti-tumor effects. To assess this, we identified several miRNAs downregulated by TGF-ß1 in PCa cell lines and selected miR-3691-3p for detailed analysis as a candidate anti-oncogene miRNA. miR-3691-3p was expressed at significantly lower levels in human PCa tissue compared with paired benign prostatic hyperplasia tissue, and its expression level correlated inversely with aggressive clinical pathological features. Overexpression of miR-3691-3p in PCa cell lines inhibited proliferation, migration, and invasion, and promoted apoptosis. The miR-3691-3p target genes E2F transcription factor 3 (E2F3) and PR domain containing 1, with ZNF domain (PRDM1) were upregulated in miR-3691-3p-overexpressing PCa cells, and silencing of E2F3 or PRDM1 suppressed PCa cell proliferation, migration, and invasion. Treatment of mice bearing PCa xenografts with a miR-3691-3p agomir inhibited tumor growth and promoted tumor cell apoptosis. Consistent with the negative regulation of E2F3 and PRDM1 by miR-3691-3p, both proteins were overexpressed in clinical PCa specimens compared with noncancerous prostate tissue. Our results indicate that TGF-ß1-regulated miR-3691-3p acts as an anti-oncogene in PCa by downregulating E2F3 and PRDM1. These results provide novel insights into the mechanisms by which TGF-ß1 contributes to the progression of PCa.

The effect of maternal poliovirus antibodies on the immune responses of infants to poliovirus vaccines.

BACKGROUND: Maternal poliovirus antibodies could provide passive immunity to the newborns from poliovirus infection during their first few months of life, but they may impair the immune responses of infants to the poliovirus vaccine as well. In our study, we pooled the data from three clinical trials of the inactivated poliovirus vaccine (IPV) based on Sabin strains to investigate the effect of maternal poliovirus antibodies on the immune responses of infants to poliovirus vaccines. METHODS: There were five groups in the pooled analysis, including low-dose Sabin IPV, medium-dose Sabin IPV, high-dose Sabin IPV, control Sabin IPV, and control Salk IPV groups. We reclassified the infants in different groups according to their maternal poliovirus antibodies by two methods, the first one included maternal antibody negative (< 1:8) and maternal antibody positive (≥1:8), and the second one included maternal antibody titer < 1:8, 1:8 ~ < 1:32 and ≥ 1:32. Then, we compared the geometric mean titers (GMTs), geometric mean antibody fold increases (GMIs) and seroconversion rates of poliovirus type-specific neutralizing antibodies after vaccination among participants with different maternal poliovirus antibody levels. RESULTS: The GMTs and GMIs of three types of poliovirus antibodies after vaccination in maternal antibody negative participants were significantly higher than those in maternal antibody positive participants. The seroconversion rates of type II and type III poliovirus antibodies in maternal antibody positive participants were significantly lower than those in maternal antibody negative participants. Among participants with maternal antibody titer < 1:8, 1:8 ~ < 1:32 and ≥ 1:32, the GMTs and GMIs of three types of poliovirus antibodies after vaccination showed a tendency to decline with the increasing of maternal antibody levels. The seroconversion rates of three types of poliovirus antibodies in participants with maternal antibody titer ≥1:32 were significantly lower than those in participants with maternal antibody titer < 1:8 and 1:8 ~ < 1:32. CONCLUSIONS: Maternal poliovirus antibodies interfered with the immune responses of infants to poliovirus vaccines, and a high level of maternal antibodies exhibited a greater dampening effect. TRIAL REGISTRATION: ClinicalTrials.gov NCT04264598 February 11, 2020; ClinicalTrials.gov NCT04264546 February 11, 2020; ClinicalTrials.gov NCT03902054 April 3, 2019. Retrospectively registered.