Immunogenicity and safety of an ORF7-deficient skin-attenuated and neuro-attenuated live vaccine for varicella: a randomised, double-blind, controlled, phase 2a trial.

BACKGROUND: The Oka varicella vaccine strain remains neurovirulent and can establish lifelong latent infection, raising safety concerns about vaccine-related herpes zoster. In this study, we aimed to evaluate the immunogenicity and safety of a skin-attenuated and neuro-attenuated varicella vaccine candidate (v7D vaccine). METHODS: We did this randomised, double-blind, controlled, phase 2a clinical trial in Jiangsu, China. Healthy children aged 3-12 years with no history of varicella infection or vaccination were enrolled and randomly assigned (1:1:1:1) to receive a single subcutaneous injection of the v7D vaccine at 3·3 log10 plaque forming units (PFU; low-dose v7D group), 3·9 log10 PFU (medium-dose v7D group), and 4·2 log10 PFU (high-dose v7D group), or the positive control varicella vaccine (vOka vaccine group). All the participants, laboratory personnel, and investigators other than the vaccine preparation and management staff were masked to the vaccine allocation. The primary outcome was assessment of the geometric mean titres (GMTs) and seroconversion rates of anti-varicella zoster virus immunoglobulin G (IgG) induced by different dose groups of v7D vaccine at 0, 42, 60, and 90 days after vaccination in the per-protocol set for humoral immune response analysis. Safety was a secondary outcome, focusing on adverse events within 42 days post-vaccination, and serious adverse events within 6 months after vaccination. This study was registered on Chinese Clinical Trial Registry, ChiCTR2000034434. FINDINGS: On Aug 18-21, 2020, 842 eligible volunteers were enrolled and randomly assigned treatment. After three participants withdrew, 839 received a low dose (n=211), middle dose (n=210), or high dose (n=210) of v7D vaccine, or the vOka vaccine (n=208). In the per-protocol set for humoral immune response analysis, the anti-varicella zoster virus IgG antibody response was highest at day 90. At day 90, the seroconversion rates of the low-dose, medium-dose, and high-dose groups of v7D vaccine and the positive control vOka vaccine group were 100·0% (95% CI 95·8-100·0; 87 of 87 participants), 98·9% (93·8-100·0; 87 of 88 participants), 97·8% (92·4-99·7; 91 of 93 participants), and 96·4% (89·8-99·2; 80 of 83 participants), respectively; the GMTs corresponded to values of 30·8 (95% CI 26·2-36·0), 31·3 (26·7-36·6), 28·2 (23·9-33·2), and 38·5 (31·7-46·7). The v7D vaccine, at low dose and medium dose, elicited a humoral immune response similar to that of the vOka vaccine. However, the high-dose v7D vaccine induced a marginally lower GMT compared with the vOka vaccine at day 90 (p=0·027). In the per-protocol set, the three dose groups of the v7D vaccine induced a similar humoral immune response at each timepoint, with no statistically significant differences. The incidence of adverse reactions in the low-dose, medium-dose, and high-dose groups of v7D vaccine was significantly lower than that in the vOka vaccine group (17% [35 of 211 participants], 20% [41 of 210 participants], and 13% [27 of 210 participants] vs 24% [50 of 208 participants], respectively; p=0·025), especially local adverse reactions (10% [22 of 211 participants], 14% [30 of 210 participants] and 9% [18 of 210 participants] vs 18% [38 of 208 participants], respectively; p=0·016). None of the serious adverse events were vaccine related. INTERPRETATION: The three dose groups of the candidate v7D vaccine exhibit similar humoral immunogenicity to the vOka vaccine and are well tolerated. These findings encourage further investigations on two-dose vaccination schedules, efficacy, and the potential safety benefit of v7D vaccine in the future. FUNDING: The National Natural Science Foundation of China, CAMS Innovation Fund for Medical Sciences, the Fundamental Research Funds for the Central Universities, and Beijing Wantai. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Immune persistence after different polio sequential immunization schedules in Chinese infants.

Trivalent oral poliovirus vaccine (tOPV) has been withdrawn and instead an inactivated poliovirus vaccine (IPV) and bivalent type 1 and type 3 OPV (bOPV) sequential immunization schedule has been implemented since 2016, but no immune persistence data are available for this polio vaccination strategy. This study aimed to assess immune persistence following different polio sequential immunization schedules. Venous blood was collected at 24, 36, and 48 months of age from participants who had completed sequential schedules of combined IPV and OPV in phase III clinical trials. The serum neutralizing antibody titers against poliovirus were determined, and the poliovirus-specific antibody-positive rates were evaluated. A total of 1104 participants were enrolled in this study. The positive rates of poliovirus type 1- and type 3-specific antibodies among the sequential immunization groups showed no significant difference at 24, 36, or 48 months of age. The positive rates of poliovirus type 2-specific antibody in the IPV-IPV-tOPV group at all time points were nearly 100%, which was significantly higher than the corresponding rates in other immunization groups (IPV-bOPV-bOPV and IPV-IPV-bOPV). Immunization schedules involving one or two doses of IPV followed by bOPV failed to maintain a high positive rate for poliovirus type 2-specific antibody.

Safety and immunogenicity of a skin- and neuro-attenuated live vaccine for varicella: a randomized, double-blind, controlled, dose-escalation and age de-escalation phase 1 clinical trial.

Background: Despite the success in decreasing varicella-related disease burden, live-attenuated Oka vaccine strain of varicella-zoster virus (vOka) remains neuro-virulence and may establish latency and reactivate, raising safety concerns. Here we aimed to evaluate the safety and immunogenicity of a skin- and neuro-attenuated varicella vaccine candidate (v7D). Methods: This is a randomized, double-blind, placebo-controlled, dose-escalation and age de-escalation phase 1 clinical trial conducted in Liuzhou, China (ChiCTR1900022284). Eligible healthy participants aged 1-49 years, with no history of varicella vaccination and had no history of varicella or herpes zoster were sequentially enrolled and allocated to subcutaneously receive one of the three doses (3.3, 3.9, and 4.2 lg PFU) of v7D, vOka or placebo in a dose-escalation and age de-escalation manner. The primary outcome was safety, assessed by adverse events/reactions within 42 days after vaccination and serious adverse events (SAEs) throughout six months after vaccination. The secondary outcome was immunogenicity, assessed by the VZV IgG antibodies measured with fluorescent antibody to membrane antigen (FAMA) assay. Findings: Between April 2019 and March 2020, totally 224 participants were enrolled. Within 42 days post-vaccination, the incidences of adverse reactions were 37.5%-38.7% in the three doses of v7D groups which were similar to that of the vOka (37.5%) and placebo (34.4%) groups. No SAE has been judged as causally related to vaccination. At 42 days post-vaccination, 100% of children aged 1-12 years in the per-protocol set of immunogenicity cohort of the v7D groups became seropositive. Meanwhile, in the intent-to-treat set of immunogenicity cohort of subjects aged 1-49 years, the geometric mean increases of the three groups of v7D vaccine were 3.8, 5.8 and 3.2, respectively, which were similar to that of the vOka vaccine group (4.4) and significantly higher than that of the placebo group (1.3). Interpretation: The candidate v7D vaccine has been preliminarily shown to be well-tolerated and immunogenic in humans. The data warrant further evaluation of the safety advantage and efficacy of v7D as a varicella vaccine. Funding: The National Natural Science Foundation of China, CAMS Innovation Fund for Medical Sciences, and Beijing Wantai CO., LTD.

Safety and immunogenicity of a bivalent HPV16/18 vaccine in Chinese females.

As global supply is still inadequate to address the worldwide requirements for HPV vaccines, we assessed the safety and immunogenicity of a new bivalent HPV16/18 vaccine. In this randomized, double-blind, placebo-controlled, phase 2 trial, healthy 9-45-year-old Chinese females in three age cohorts (600 aged 9-17 years; 240 aged 18-26 years; 360 aged 27-45 years) were randomized 1:1 to receive three doses (0,2,6 months) of HPV16/18 vaccine or placebo. We measured neutralizing antibodies against HPV 16 and 18 at 7 months and monitored safety to 12 months in all age cohorts; 9-17-year-old girls were monitored for safety and immunogenicity to 48 months. In vaccinees, 99.8% seroconverted for HPV 16 and 18 types at 7 months; respective GMTs of 5827 (95% CI: 5249, 6468) and 4223 (3785, 4713) were significantly (p < .001) higher than controls for all comparisons. GMTs in the 9-17-year-olds, which were significantly higher than in older women at 7 months, gradually declined to 48 months but remained higher than placebo with seropositivity rates maintained at 98.5% and 97.6% against HPV 16 and 18, respectively. Adverse events occurred at similar rates after vaccine and placebo (69.8% vs. 72.5%, p = .308), including solicited local reactions and systemic adverse events which were mainly mild-to-moderate. The bivalent HPV16/18 vaccine was well tolerated and induced high levels of neutralizing antibodies in all age groups which persisted at high levels to 48 months in the 9-17-year-old age group which would be the target for HPV vaccination campaigns.

Safety and immunogenicity of a pichia pastoris-expressed bivalent human papillomavirus (types 16 and 18) L1 virus-like particle vaccine in healthy Chinese women aged 9-45 years: A randomized, double-blind, placebo-controlled phase 1 clinical trial.

BACKGROUND: We evaluated the safety and immunogenicity of high and low doses of a novel pichia pastoris-expressed bivalent (types 16 and 18) human papillomavirus (HPV) virus-like particle vaccine. METHODS: In this randomized, double-blind, placebo-controlled phase 1 trial, we enrolled 160 healthy females aged 9-45 years in Guangxi, China who were randomized (1:1:2) to receive either low (0.5 mL) or high (1.0 mL) dosages of bivalent HPV vaccine, or placebo (aluminum adjuvant) in a 0, 2, 6 months schedule. Adverse events and other significant conditions that occurred within 30 days after each vaccination were recorded throughout the trial. Sera were collected at days 0, 60, 180 and 210 to measure anti-HPV 16/18 neutralizing antibodies. RESULTS: A total of 160 participants received at least one dose of the HPV vaccine and 152 completed the three dose vaccination series. Reporting rates of adverse events in placebo, low dose (0.5 mL) and high dose (1.0 mL) groups were 47.5 %, 55.0 % and 55.0 %, respectively. No serious adverse events occurred during this trial. 100 % of the participants who received three doses of the HPV vaccine produced neutralizing antibodies against HPV 16/18 vaccine. For HPV 16 and HPV 18, the geometric mean titers (GMTs) were similar between the low dose group (GMTHPV 16 = 10816 [95 % CI: 7824-14953]), GMTHPV 18 = 3966 [95 % CI: 2693-5841]) and high dose group (GMT HPV 16 = 14482 [95 % CI: 10848-19333], GMT HPV 18 = 3428 [95 % CI: 2533-4639]). CONCLUSION: The pichia pastoris-expressed bivalent HPV vaccine was safe and immunogenic in Chinese females aged 9-45 years. The low dosage (0.5 mL) was selected for further immunogenicity and efficacy study.

Comparison of the safety and persistence of immunogenicity of bivalent HPV16/18 vaccine in healthy 9-14-year-old and 18-26-year-old Chinese females: A randomized, double-blind, non-inferiority clinical trial.

BACKGROUND: We assessed the safety, immunogenicity and antibody persistence of two- and three-dose schedules of the novel bivalent HPV16/18 vaccine (HPV-2, Walrinvax) in the per-protocol target population of initially seronegative 9-14 year-old girls, including a non-inferiority comparison with the three-dose schedule in 18-26 year-old women. METHODS: This randomized phase 3b trial in Guangxi Zhuang Autonomous Region, China, involved healthy Chinese females in two age cohorts; 600 girls aged 9-14 years and 300 women aged 18-26 years. Girls were randomly assigned (1:1) to receive either two (Months 0,6) or three (Months 0,2,6) intramuscular doses of HPV-2. All participants were monitored for immunogenicity as neutralizing antibodies up to 36 months. Primary objectives were non-inferiority analyses of immunogenicity between two- and three-dose girl groups and adult women at Month 7; safety assessments were based on participant-completed diary cards. RESULTS: All groups demonstrated marked increases in neutralizing antibodies against HPV 16 and 18 that persisted above baseline to 36 months. Month 7 responses in both girl groups were non-inferior to those in the women and were statistically higher after two-doses than girls or women who received three doses. GMTs waned after month 7, but then maintained a plateau level until month 36. Vaccination was well tolerated in all groups with no serious adverse events reported. CONCLUSIONS: Immune responses to two doses of HPV-2 vaccine in adolescent girls were non-inferior to those after three doses in young women, an age cohort in which clinical efficacy of HPV-2 against cervical cancer has been demonstrated.

Treat-to-Target urate-lowering therapy in primary gout patients: A real-world retrospective study at a dedicated gout clinic in China.

BACKGROUND: Gout is the most common inflammatory arthritis affecting 1.1% of the population in mainland China with a higher prevalence in coastal areas. OBJECTIVE: The purpose of the study was to investigate the clinical outcomes following urate-lowering therapy (ULT) in a real-world group study of primary gout patients in China. METHODS: Electronic medical records of all the gout patients (n= 1588) that visited the Clinical Medical Center of Gout of the Affiliated Hospital of Qingdao University from September 2016 to February 2018 were analyzed in this study. The patients were treated with a standard treat-to-target (T2T) ULT strategy according to the 2016 EULAR Guidelines. Clinical data were collected in the first visit and one-month (defined as the baseline of ULT), 7-month, and 13-month follow-ups were completed. RESULTS: Amongst the patients in the study, 92.70% accepted ULT and 82.93% completed ULT for 3 months, 63.54% for 6 months, and 40.49% (n= 643) for 12 months. Further analysis of the 643 patients included the following data: the sUA level reduced at month 7 and reduced further at month 13. The gout flares, patient global pain visual analogue score, and health assessment questionnaire score improved at month 7 but did not improve further at month 13, and the index tophus size did not.

Low toxicity and high immunogenicity of an inactivated vaccine candidate against COVID-19 in different animal models.

The ongoing COVID-19 pandemic is causing huge impact on health, life, and global economy, which is characterized by rapid spreading of SARS-CoV-2, high number of confirmed cases and a fatality/case rate worldwide reported by WHO. The most effective intervention measure will be to develop safe and effective vaccines to protect the population from the disease and limit the spread of the virus. An inactivated, whole virus vaccine candidate of SARS-CoV-2 has been developed by Wuhan Institute of Biological Products and Wuhan Institute of Virology. The low toxicity, immunogenicity, and immune persistence were investigated in preclinical studies using seven different species of animals. The results showed that the vaccine candidate was well tolerated and stimulated high levels of specific IgG and neutralizing antibodies. Low or no toxicity in three species of animals was also demonstrated in preclinical study of the vaccine candidate. Biochemical analysis of structural proteins and purity analysis were performed. The inactivated, whole virion vaccine was characterized with safe double-inactivation, no use of DNases and high purity. Dosages, boosting times, adjuvants, and immunization schedules were shown to be important for stimulating a strong humoral immune response in animals tested. Preliminary observation in ongoing phase I and II clinical trials of the vaccine candidate in Wuzhi County, Henan Province, showed that the vaccine is well tolerant. The results were characterized by very low proportion and low degree of side effects, high levels of neutralizing antibodies, and seroconversion. These results consistent with the results obtained from preclinical data on the safety.

Tuning Anderson localization of edge-mode graphene plasmons in randomly gated nanoribbons.

Edge-mode graphene plasmons (EGPs) supported by graphene nanoribbons are highly confined, and they can show versatile tunability under electrostatic bias. In order to efficiently enhance and actively control the near-field intensity in integrated plasmonic devices, we theoretically study Anderson localization of EGPs in a graphene nanoribbon with an underlying electrode array in this work. By randomly arranging the electrodes in the array, positional disorder is introduced in the graphene nanoribbon system. Consequently, the Anderson localization of EGPs occurs with an exponentially decreased electric field, reduced propagation length, and rapid disappearance of the cross-correlation coefficient. Physically, inhomogeneous gating effectively creates a disordered distribution of Fermi levels in the graphene nanoribbon, which provides adequate fluctuation of the effective refractive index and results in strong localization of the EGPs at mid-infrared regime. By changing electrode array arrangements, the EGPs can be trapped at distinct locations in the nanoribbon. Further considering that the Fermi-level disorder can be introduced by randomly modulating the electrostatic bias, we apply different gate voltages at different electrodes in the array. Electrically tunable Anderson localization of EGPs are eventually realized in those randomly gated nanoribbons. Moreover, by combining both the positional and Fermi-level disorders in the system, the Anderson localization becomes more actively controlled in this electrically gated graphene nanoribbons. It is shown that the local field can be selectively trapped at single distinct location, or even several locations along the graphene nanoribbon. This investigation extends the Anderson localization to the EGPs in the mid-infrared range and enriches the graphene-based active plasmonic devices.

Immunogenicity of an Escherichia coli-produced bivalent human papillomavirus vaccine under different vaccination intervals.

A new Escherichia coli-produced human papillomavirus (HPV)-16/18 vaccine has been shown to be safe and highly efficacious and was recently licensed in China. As a post hoc analysis of the phase III trial, this study aimed to assess the impact of vaccination time deviations on the specific antibody response and guide the better usage of this vaccine in the real world. A total of 3689 healthy women aged 18-45 years old were randomly assigned to receive the bivalent HPV-16/18 vaccine according to a 0-, 1- and 6-month schedule with a wide vaccination interval. The first vaccination interval between the 1st and 2nd doses (the 1st interval) was divided into three groups: 28-40 d, 41-50 d and 51-60 d. The second vaccination interval between the 2nd and 3rd doses (the 2nd interval) was divided into three groups: 103-139 d, 140-160 d and 161-198 d. The reverse cumulative curves for the IgG of the three groups with different 1st vaccination intervals or with different 2nd vaccination intervals at month 7 almost overlapped for both HPV-16 and HPV-18. Compared with the standard vaccination schedule (a 1st interval of 28-40 d and a 2nd interval of 140-160 d) subgroup, all the subgroups had GMC ratios greater than 0.83, with the lower limit of 95% CIs higher than 0.64. In conclusion, a slight deviation in the vaccination time of the 2nd and 3rd doses has only a minor, insignificant impact on the immune response induced by the Escherichia coli-produced HPV-16/18 vaccine.

Efficacy, Safety, and Immunogenicity of an Escherichia coli-Produced Bivalent Human Papillomavirus Vaccine: An Interim Analysis of a Randomized Clinical Trial.

BACKGROUND: The high cost and insufficient supply of human papillomavirus (HPV) vaccines have slowed the pace of controlling cervical cancer. A phase III clinical trial was conducted to evaluate the efficacy, safety, and immunogenicity of a novel Escherichia coli-produced bivalent HPV-16/18 vaccine. METHODS: A multicenter, randomized, double-blind trial started on November 22, 2012 in China. In total, 7372 eligible women aged 18-45 years were age-stratified and randomly assigned to receive three doses of the test or control (hepatitis E) vaccine at months 0, 1, and 6. Co-primary endpoints included high-grade genital lesions and persistent infection (over 6 months) associated with HPV-16/18. The primary analysis was performed on a per-protocol susceptible population of individuals who were negative for relevant HPV type-specific neutralizing antibodies (at day 0) and DNA (at day 0 through month 7) and who received three doses of the vaccine. This report presents data from a prespecified interim analysis used for regulatory submission. RESULTS: In the per-protocol cohort, the efficacies against high-grade genital lesions and persistent infection were 100.0% (95% confidence interval = 55.6% to 100.0%, 0 of 3306 in the vaccine group vs 10 of 3296 in the control group) and 97.8% (95% confidence interval = 87.1% to 99.9%, 1 of 3240 vs 45 of 3246), respectively. The side effects were mild. No vaccine-related serious adverse events were noted. Robust antibody responses for both types were induced and persisted for at least 42 months. CONCLUSIONS: The E coli-produced HPV-16/18 vaccine is well tolerated and highly efficacious against HPV-16/18-associated high-grade genital lesions and persistent infection in women.

Immunogenicity noninferiority study of 2 doses and 3 doses of an Escherichia coli-produced HPV bivalent vaccine in girls vs. 3 doses in young women.

A new HPV-16/18 bivalent vaccine expressed by the Escherichia coli has been proven to be efficacious in adult women. A randomized, immunogenicity noninferiority study of this candidate vaccine was conducted in December 2015 in China. Girls aged 9-14 years were randomized 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) received 3 doses. The objectives included noninferiority analysis of the IgG geometric mean concentration (GMC) ratio (95% CI, lower bound>0.5) to HPV-16 and HPV-18 at month 7 in girls compared with women. In the per-protocol set, the GMC ratio of IgG was noninferior for girls aged 9-17 years receiving 3 doses compared with women (1.76 (95% CI, 1.56, 1.99) for HPV-16 and 1.93 (95% CI, 1.69, 2.21) for HPV-18) and noninferior for girls aged 9-14 years receiving 2 doses compared with women (1.45 (95% CI, 1.25, 1.62) for HPV-16 and 1.17 (95% CI, 1.02, 1.33) for HPV-18). Noninferiority was also demonstrated for neutralizing antibodies. The immunogenicity of the HPV vaccine in girls receiving 3 or 2 doses was noninferior compared with that in young adult women.

Lot-to-lot consistency study of an Escherichia coli-produced bivalent human papillomavirus vaccine in adult women: a randomized trial.

An Escherichia. coli-produced HPV-16/18 bivalent vaccine has been proved to be well-tolerated and highly efficacious against diseases associated with vaccine HPV types. As a part of the multi-center, randomized, double-blind phase III clinical trial, this lot-to-lot consistency study aimed to assess the safety and immunogenicity consistency of this novel HPV vaccine, which is also one of the objectives of the phase III trial. A total of 3689 healthy women aged 18-45 years were enrolled and randomly assigned 1:1:1 to three lots of the HPV vaccine groups. The primary outcomes were the IgG antibody level at 1 month after the last dose (month 7). In the immunogenicity per-protocol set (PPS), almost all of the participants seroconverted at month 7 and remained seropositive at month 42. For each paired comparison of the three lot groups, the two-sides of 90% CIs of GMC ratios for both IgG and neutralizing antibodies for HPV-16 and HPV-18 at month 7 were within the equivalence interval [0.5, 2]. Lot consistency was also demonstrated at month 42. The majority of recorded solicited reactions were mild or moderate. The incidences of solicited reactions of Lot 2 and Lot 3 were slightly higher than Lot 1. However, the incidences of solicited reactions of ≥ grade 3 and solicited reactions by symptoms were all similar among the three lot groups. None of the SAEs was considered related to vaccination by the investigator. In conclusion, this study demonstrates lot-to-lot consistency of the 3 consecutive lots of the E. coli-produced HPV-16/18 bivalent vaccine.

Sequence Analysis and Comparison of the Key Genes of Domestic Live Attenuated Varicella Vaccine.

Objective To analyze the safety and consistency of domestic live attenuated varicella vaccines (LAVVs) at gene level.Methods The key genes (ORF38,ORF54,and ORF62) of LAVVs produced by four Chinese manufacturers were amplified by polymerase chain reaction (PCR) and sequenced.The sequencing results were compared with the sequences of Dumas,P-Oka,and V-Oka strains in GenBank and with the sequences of Varilrix (GSK) and Varivax (Merck).Results The ORF38 and ORF54 gene sequences of four domestic LAVVs were the same as each other and completely consistent with the sequences of V-Oka and Varilrix;however,it was different from Varivax (Merck) at one site.The ORF62 gene sequences of four domestic LAVVs were similar,and had individual nucleotide differences with V-Oka,Varilrix(GSK),and Varivax (Merck).Conclusions The sequences of ORF38,ORF54,and ORF62 of four domestic LAVVs are almost the same,showing good stability.They have small differences with V-Oka,Varilrix(GSK),and Varivax (Merck),without introducing new mutations.

Primary and booster vaccination with an inactivated poliovirus vaccine (IPV) is immunogenic and well-tolerated in infants and toddlers in China.

INTRODUCTION: Replacing live-attenuated oral poliovirus vaccines (OPV) with inactivated poliovirus vaccines (IPV) is part of the global strategy to eradicate poliomyelitis. China was declared polio-free in 2000 but continues to record cases of vaccine-associated-poliomyelitis and vaccine-derived-poliovirus outbreaks. Two pilot safety studies and two larger immunogenicity trials evaluated the non-inferiority of IPV (Poliorix™, GSK Vaccines, Belgium) versus OPV in infants and booster vaccination in toddlers primed with either IPV or OPV in China. METHODS: In pilot safety studies, 25 infants received 3-dose IPV primary vaccination (Study A, www.clinicaltrial.gov NCT00937404) and 25 received an IPV booster after priming with three OPV doses (Study B, NCT01021293). In the randomised, controlled immunogenicity and safety trial (Study C, NCT00920439), infants received 3-dose primary vaccination with IPV (N=541) or OPV (N=535) at 2,3,4 months of age, and a booster IPV dose at 18-24 months (N=470, Study D, NCT01323647: extension of study C). Blood samples were collected before and one month post-dose-3 and booster. Reactogenicity was assessed using diary cards. Serious adverse events (SAEs) were captured throughout each study. RESULTS: Study A and B showed that IPV priming and IPV boosting (after OPV) was safe. Study C: One month post-dose-3, all IPV and ≥ 98.3% OPV recipients had seroprotective antibody titres towards each poliovirus type. The immune response elicited by IPV was non-inferior to Chinese OPV. Seroprotective antibody titres persisted in ≥ 94.7% IPV and ≥ 96.1% OPV recipients at 18-24 months (Study D). IPV had a clinically acceptable safety profile in all studies. Grade 3 local and systemic reactions were uncommon. No SAEs were related to IPV administration. CONCLUSION: Trivalent IPV is non-inferior to OPV in terms of seroprotection (in the Chinese vaccination schedule) in infant and toddlers, with a clinically acceptable safety profile.

Immunogenicity of Two Different Sequential Schedules of Inactivated Polio Vaccine Followed by Oral Polio Vaccine Versus Oral Polio Vaccine Alone in Healthy Infants in China.

BACKGROUND: Two vaccination schedules where inactivated polio vaccine (IPV) was followed by oral polio vaccine (OPV) were compared to an OPV-only schedule. METHODS: Healthy Chinese infants received a 3-dose primary series of IPV-OPV-OPV (Group A), IPV-IPV-OPV (Group B), or OPV-OPV-OPV (Group C) at 2, 3, and 4 months of age. At pre-Dose 1, 1-month, and 14-months post-Dose 3, polio 1, 2, and 3 antibody titers were assessed by virus-neutralizing antibody assay with Sabin or wild-type strains. Adverse events were monitored. RESULTS: Anti-polio 1, 2, and 3 titers were ≥8 (1/dil) in >99% of participants, and Group A and Group B were noninferior to Group C at 1-month post-Dose 3 as assessed by Sabin strain-based assay (SSBA). In Group A 1-month post-Dose 3, there was no geometric mean antibody titers (GMT) differences for types 1 and 3; type 2 GMTs were ≈3-fold higher by wild-type strain-based assay (WTBA) versus SSBA. For Group B, GMTs were ≈1.7- and 3.6-fold higher for types 1 and 2 via WTBA, while type 3 GMTs were similar. For Group C, GMTs were ≈6.3- and 2-fold higher for types 1 and 3 with SSBA, and type 2 GMTs were similar. Antibodies persisted in >96.6% of participants. Adverse event incidence in each group was similar. CONCLUSIONS: A primary series of 1 or 2 IPV doses followed by 2 or 1 OPV doses was immunogenic and noninferior to an OPV-only arm. SSBA was better at detecting antibodies elicited by OPV with antibody titers correlated to the number of OPV doses (NCT01475539).

Genetic polymorphisms in the PDZK1 gene and susceptibility to gout in male Han Chinese: a case-control study.

PDZK1 acts as a scaffolding protein for a large variety of transporter and regulatory proteins, and has been identified in the kidney. The PDZK1 locus has been determined to be associated with the serum urate concentration. However, the evidence supporting this protein's association with gout is equivocal. In the current study, we investigated the association between two single nucleotide polymorphisms (SNPs) (rs12129861 and rs1967017) in the PDZK1 gene with gout in a male Chinese Han population. A total of 824 subjects were enrolled in this case-control study (400 gout cases and 424 controls). PDZK1 genotyping was carried out by polymerase chain reaction (PCR) and ligase detection reaction (LDR) assays methods. The relationships were evaluated using the pooled odds ratios (ORs) and their 95 % confidence intervals (CI). The results of our case-control study demonstrated that the gout and control groups exhibited significant differences in the distribution of genotypes at rs12129861 (OR = 0.727, P = 0.015) and rs1967017 (OR = 0.705, P = 0.016), suggesting that PDZK1 genetic polymorphisms were associated with increased risks of gout in male Han Chinese. However, there were no differences in the distribution of genotypes at rs12129861 (odds ratio (OR) = 0.744, P > 0.05) and rs1967017 (OR = 0.706, P > 0.05) in patients with gout with kidney stones and without kidney stones.

Polymorphisms in GCKR, SLC17A1 and SLC22A12 were associated with phenotype gout in Han Chinese males: a case-control study.

BACKGROUND: Gout is a common arthritic disease resulting from elevated serum uric acid (SUA) level. A large meta-analysis including 28,141 individuals identified nine single nucleotide polymorphisms (SNPs) associated with altered SUA level in a Caucasian population. However, raised SUA level alone is not sufficient for the development of gout arthritis and most of these SNPs have not been studied in a Han Chinese population. Here, we performed a case-control association analysis to investigate the relationship between these SUA correlated SNPs and gout arthritis in Han Chinese. METHODS: A total of 622 ascertained gout p9atients and 917 healthy controls were genotyped. Genome-wide significant SNPs, rs12129861, rs780094, rs734553, rs742132, rs1183201, rs12356193, rs17300741 and rs505802 in the previous SUA study, were selected for our analysis. RESULTS: No deviation from the Hardy-Weinberg equilibrium was observed either in the case or control cohorts (corrected p > 0.05). Three SNPs, rs780094 (located in GCKR, corrected p = 1.78E(-4), OR = 0.723), rs1183201 (located in SLC17A1, corrected p = 1.39E(-7), OR = 0.572) and rs505802 (located in SLC22A12, corrected p = 0.007, OR = 0.747), were significantly associated with gout on allelic level independent of potential cofounding traits. While the remaining SNPs were not replicated. We also found significant associations of uric acid concentrations with these three SNPs (rs780094 in GCKR, corrected p = 3.94E(-5); rs1183201 in SLC17A1, corrected p = 0.005; rs505802 in SLC22A12, corrected p = 0.003) and of triglycerides with rs780094 (located in GCKR, corrected p = 2.96E(-4)). Unfortunately, SNP-SNP interactions for these three significant SNPs were not detected (rs780094 vs rs1183201, p = 0.402; rs780094 vs rs505802, p = 0.434; rs1183201 vs rs505802, p = 0.143). CONCLUSIONS: Three SUA correlated SNPs in Caucasian population, rs780094 in GCKR, rs1183201 in SLC17A1 and rs505802 in SLC22A12 were confirmed to be associated with gout arthritis and uric acid concentrations in Han Chinese males. Considering genetic differences among populations and complicated pathogenesis of gout arthritis, more validating tests in independent populations and relevant functional experiments are suggested in future.