A phase 3 randomized, open-label study evaluating the immunogenicity and safety of concomitant and staggered administration of a live, pentavalent rotavirus vaccine and an inactivated poliomyelitis vaccine in healthy infants in China.

This open-label, randomized, phase 3 study in China (V260-074; NCT04481191) evaluated the immunogenicity and safety of concomitant and staggered administration of three doses of an oral, live, pentavalent rotavirus vaccine (RV5) and three doses of an intramuscular, inactivated poliomyelitis vaccine (IPV) in 400 healthy infants. The primary objective was the non-inferiority of neutralizing antibody (nAb) responses in the concomitant- versus the staggered-use groups. Antibody responses were measured at baseline and 1-month post-dose 3 (PD3). Parents/legal guardians recorded adverse events for 30 or 15 d after study vaccinations in the concomitant-use or staggered-use groups, respectively. At PD3, >98% of participants seroconverted to all three poliovirus types, and the primary objective was met as lower bounds of the two-sided 95% CI for between-group difference in nAb seroconversion percentages ranged from - 4.3% to - 1.6%, for all poliovirus types, p < .001. At PD3, geometric mean titers (GMTs) of nAb responses to poliovirus types 1, 2, and 3 in the concomitant-use group and the staggered-use group were comparable; 100% of participants had nAb titers ≥1:8 and ≥1:64 for all poliovirus types. Anti-rotavirus serotype-specific IgA GMTs and participants with ≥3-fold rise in postvaccination titers from baseline were comparable between groups. Administration of RV5 and IPV was well tolerated with comparable safety profiles in both groups. The immunogenicity of IPV in the concomitant-use group was non-inferior to the staggered-use group and RV5 was immunogenic in both groups. No safety concerns were identified. These data support the concomitant use of RV5 and IPV in healthy Chinese infants.

Immunogenicity and safety of the 9-valent human papillomavirus vaccine in Chinese females 9-45 years of age: A phase 3 open-label study.

BACKGROUND: The 9-valent human papillomavirus (9vHPV; HPV6/11/16/18/31/33/45/52/58) vaccine was approved for use in Chinese women aged 16-26 years in 2018. This phase 3, open-label study (NCT03903562) compared 9vHPV vaccine immunogenicity and safety in Chinese females aged 9-19 years and 27-45 years with Chinese females aged 20-26 years; we report results from day 1 through 1 month post-Dose 3. The study will continue through 54 months post-Dose 3 to assess antibody persistence in Chinese girls aged 9-19 years. METHODS: Participants aged 9-45 years received three doses of the 9vHPV vaccine. Geometric mean titers (GMTs) and seroconversion percentages for anti-HPV6/11/16/18/31/33/45/52/58 antibodies were determined by competitive Luminex immunoassay in serum samples obtained at day 1 and 1 month post-Dose 3. Adverse events (AEs) within 30 days post-vaccination and serious AEs (SAEs) occurring at any time were recorded. RESULTS: In total, 1990 participants (690 aged 9-19 years; 650 aged 20-26 years; 650 aged 27-45 years) were enrolled. At 1 month post-Dose 3, >99% of participants in the per-protocol immunogenicity population seroconverted to each vaccine HPV type. Anti-HPV6/11/16/18/31/33/45/52/58 antibody GMTs in the 9-19-year age group were non-inferior to those in participants aged 20-26 years. Anti-HPV6/11/16/18/31/33/45/52/58 seroconversion percentages in the 27-45-year age group were non-inferior to those in participants aged 20-26 years. Injection-site and systemic AEs were reported by 43.3% and 50.9%, 50.5% and 57.1%, and 43.8% and 43.4% of participants aged 9-19, 20-26, and 27-45 years, respectively. There were no vaccine-related SAEs, discontinuations due to AEs, and deaths. CONCLUSION: Antibody responses induced by 9vHPV vaccination in Chinese females aged 9-19 years and 27-45 years were non-inferior to those in Chinese females aged 20-26 years. The vaccine was generally well tolerated. CLINICALTRIALS: gov Identifier: NCT03903562.

Immunogenicity and safety of the quadrivalent human papillomavirus vaccine in Chinese females aged 9 to 26 years: A phase 3, open-label, immunobridging study.

BACKGROUND: The quadrivalent human papillomavirus (qHPV; HPV6/11/16/18) vaccine was approved for use in Chinese women aged 20-45 years in 2017. This Phase 3, open-label study (NCT03493542) aimed to assess immunogenicity and safety of the qHPV vaccine in Chinese girls aged 9-19 years versus Chinese young women aged 20-26 years; we report results from Day 1 through Month 7. The study will continue through Month 60 to assess antibody persistence in Chinese girls aged 9-19 years. METHODS: Participants aged 9-26 years received three doses of the qHPV vaccine (Day 1, Month 2, Month 6). Geometric mean titers (GMTs) and seroconversion percentages for anti-HPV6/11/16/18 antibodies were determined by competitive Luminex immunoassay (cLIA) in serum samples obtained on Day 1 and at Month 7. Injection-site adverse events (AEs) and systemic AEs within 30 days post-vaccination, and serious AEs (SAEs) occurring at any time during the study, were recorded. RESULTS: In total, 766 participants (383 aged 9-19 years; 383 aged 20-26 years) were enrolled and received ≥1 vaccine dose. All participants in the per-protocol immunogenicity population of both age groups seroconverted to each of the vaccine HPV types at Month 7. Anti-HPV6/11/16/18 antibody GMTs at Month 7 in participants aged 9-19 years were non-inferior to those in participants aged 20-26 years. Injection-site AEs and systemic AEs were reported by 36.6% and 49.3% of 9-19-year-olds, and 40.7% and 54.8% of 20-26-year-olds, respectively. There were no vaccine-related SAEs. No participants discontinued the vaccine due to an AE and no deaths were reported. CONCLUSION: Antibody responses induced by the 3-dose qHPV vaccination regimen in Chinese girls aged 9-19 years were non-inferior to those in Chinese young women aged 20-26 years. The vaccine was generally well tolerated in the study population. ClinicalTrials.gov Identifier: NCT03493542.

Immunogenicity of pentavalent rotavirus vaccine in Chinese infants.

BACKGROUND: A phase III, randomized, double-blind, placebo-controlled clinical study was conducted in China to assess the efficacy, safety, and immunogenicity of the pentavalent rotavirus vaccine (RotaTeqTM, RV5) among Chinese infants. The efficacy and safety data have been previously reported. This report presents the immunogenicity data of the study. METHODS: 4,040 infants aged 6-12 weeks were randomly assigned in a 1:1 ratio to receive 3 oral doses of RV5 or placebo. Trivalent oral poliovirus vaccine (tOPV) and diphtheria, tetanus, and acellular pertussis vaccine (DTaP) were administered in a staggered-use (N = 3,240) or concomitant-use (N = 800) schedule. Immunogenicity of RV5 was evaluated in 800 participants (400 participants from each staggered- and concomitant-use immunogenicity subgroup). Geometric mean titers (GMTs) and seroresponse rates (≥3-fold rise from baseline to PD3) were measured for anti-rotavirus IgA in the staggered- and concomitant-use subgroups and measured for serum neutralizing antibodies (SNAs) to human rotavirus serotypes G1, G2, G3, G4, P1A[8] in the staggered-use subgroup. Immune responses to tOPV and DTaP co-administered with RV5 were also evaluated in the concomitant-use immunogenicity subgroup. (ClinicalTrials.gov registry: NCT02062385) RESULTS: The PD3 GMT and seroresponse rate of anti-rotavirus IgA were higher in the RV5 group (82.42 units/mL, 89.4%) compared to the placebo group (0.33 units/mL, 10.1%). Rotavirus type-specific SNA responses were also higher in the RV5 group compared to the placebo group. In the concomitant-use subgroup, the seroprotection rates of anti-poliovirus type 1, 2, 3 in the participants who received RV5 were non-inferior to those who received placebo, and the antibody responses to DTaP antigens were comparable between the two vaccination groups. CONCLUSIONS: RV5 was immunogenic in Chinese infants. Immune responses induced by tOPV and DTaP were not affected by the concomitant use of RV5.

Safety of a quadrivalent human papillomavirus vaccine in a Phase 3, randomized, double-blind, placebo-controlled clinical trial among Chinese women during 90 months of follow-up.

BACKGROUND: A quadrivalent human papillomavirus (qHPV) vaccine (HPV6/11/16/18) has demonstrated efficacy and acceptable safety in international studies. However, these studies did not include participants from mainland China, which has a substantial burden of HPV-related disease. This is the first safety report with a follow-up period of up to 90 months from a randomized, double-blind, placebo-controlled trial of qHPV vaccine in Chinese women 20-45 years of age. METHODS: Participants were randomized 1:1 to receive three doses of qHPV vaccine or placebo (Day1, Month 2, and Month 6). Efficacy outcomes are reported elsewhere. Injection-site and systemic adverse events (AEs) were collected using vaccination report cards (VRCs) for 15 days following each vaccination. Serious AEs (SAEs), pregnancy outcomes, new medical conditions, and fetal/infant SAEs were collected during the entire study. RESULTS: Of 3006 participants randomized, AEs were reported by 926 (61.8%) qHPV vaccine recipients and 856 (57.1%) placebo recipients over the entire study. Four participants (two in each group) discontinued the study vaccination due to AEs that were considered vaccination-related. Within 15 days following any vaccination, injection-site AEs prompted for on the VRC were more frequent among qHPV vaccine recipients (37.6% vs 27.8%), and systemic AEs prompted for on the VRC were similar in frequency between qHPV vaccine and placebo groups (46.8% vs 45.1%). Thirty-eight and 43 participants reported SAEs in qHPV vaccine and placebo groups, respectively. No SAE was considered qHPV vaccine-related. Pregnancy outcomes, fetal/infant SAEs, and new medical conditions were generally similar in frequency between the qHPV vaccine and placebo groups, and within normal ranges. CONCLUSION: The qHPV vaccine was well tolerated and demonstrated a favorable safety profile in Chinese women 20-45 years of age, consistent with findings from global trials and safety surveillance studies. TRIAL REGISTRATION: clinicaltrials.gov; NCT00834106.

Efficacy of quadrivalent human papillomavirus vaccine against persistent infection and genital disease in Chinese women: A randomized, placebo-controlled trial with 78-month follow-up.

BACKGROUND: A quadrivalent human papillomavirus vaccine (qHPV; HPV6/11/16/18) has demonstrated efficacy and effectiveness worldwide. We report qHPV vaccine efficacy for up to 6.5 years after first administration among Chinese women 20-45 years of age. METHODS: In this randomized, double-blind, placebo-controlled, multicenter, Phase 3 study (NCT00834106), women were randomized 1:1 to receive 3 doses of qHPV vaccine or placebo (Day 1, Month 2, Month 6). Endo-ecto-cervical and external genital swabs were collected for HPV testing and gynecologic examinations, and cervical cytology testing were performed at Day 1 and Months 7, 12, 18, 24, 30, 42, 54, 66, and 78. Any abnormality in cytology testing would trigger colposcopy examination and cervical biopsy, if necessary. Efficacy against genital disease, persistent infection, and the composite endpoint was assessed. Primary efficacy analyses were conducted in the per-protocol efficacy (PPE) population. RESULTS: Of 3006 participants randomized, 2759 (91.8%) and 2374 (79%) completed the Month 30 and Month 78 visits, respectively. At Month 78, efficacy among women aged 20-45 years was 100% (95% CI: 32.3, 100; 0 vs 7 cases) and 100% (95% CI: 70.9, 100; 0 vs 14 cases) against HPV16/18-related cervical intraepithelial neoplasia Grade 2 or 3, adenocarcinoma in situ, and cervical cancer (CIN 2+) and HPV6/11/16/18-related CIN 1+, respectively, in the PPE population. The efficacy against cervical 6-month and 12-month persistent infection was 91.6% (95% CI: 66.0, 99.0) and 97.5% (95% CI: 85.1, 99.9) at Month 30 and Month 78, respectively, in the PPE population. The vaccine also reduced the rate of cervical cytology abnormalities associated with HPV6/11/16/18, with an efficacy of 94.0% (95% CI: 81.5, 98.8). The vaccine was generally well tolerated (reported separately). CONCLUSION: The qHPV vaccine is efficacious against endpoints of persistent infection and genital precancerous lesions in Chinese women aged 20-45 years.

Evaluation on the persistence of anti-HPV immune responses to the quadrivalent HPV vaccine in Chinese females and males: Up to 3.5 years of follow-up.

BACKGROUND: This was an extension study of a randomized, double-blind, placebo-controlled immunogenicity and safety study of the quadrivalent human papillomavirus (qHPV) (HPV 6, 11, 16, and 18) vaccine conducted in Chinese female subjects aged 9-45 years and male subjects aged 9-15 years. To investigate the persistence of anti-HPV 6, -11, -16, and -18 responses among Chinese subjects, subjects enrolled in the base study were followed up at around month 42 (approximately 3.5 years after vaccination). METHODS: Among 600 subjects enrolled in the base study, a total of 468 subjects consented for participation in the extension study. Anti-HPV 6, -11, -16, and -18 antibodies were detected by the competitive Luminex immunoassay (cLIA) and total IgG Luminex immunoassay (IgG LIA). RESULTS: Among the female subjects who received the qHPV vaccine, the proportions of subjects remained seropositive were high with both the cLIA and IgG LIA for HPV type 6, 11, and 16 through approximately 42 months following the first dose vaccination. For HPV 18, the seropositivity rate remained high as 82.0% with the IgG LIA, while it decreased to 53.6% with the cLIA, which was similar to the findings observed in other studies. The seropositivity rates remained high at month 42 for all qHPV types with both the cLIA and IgG LIA among the male subjects. CONCLUSIONS: Administration of a 3-dose regimen of qHPV vaccine induces durable anti-HPV 6, anti-HPV 11, anti-HPV 16, and anti-HPV 18 responses among Chinese subjects for at least 3.5 years after vaccination. ClinicalTrials.gov registry:NCT01427777.

Efficacy and safety of a pentavalent live human-bovine reassortant rotavirus vaccine (RV5) in healthy Chinese infants: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: A randomized, double-blind, placebo-controlled multicenter trial was conducted in healthy Chinese infants to assess the efficacy and safety of a pentavalent live human-bovine reassortant rotavirus vaccine (RotaTeq™, RV5) against rotavirus gastroenteritis (RVGE). METHODS: 4040 participants aged 6-12weeks were enrolled and randomly assigned to either 3 oral doses of RV5 (n=2020) or placebo (n=2020), administered ∼4weeks apart. The participants also received OPV and DTaP in a concomitant or staggered fashion. The primary objective was to evaluate vaccine efficacy (VE) against naturally-occurring RVGE at least 14days following the third dose. Key secondary objectives included: VE against naturally-occurring severe RVGE and VE against severe and any-severity RVGE caused by rotavirus serotypes contained in the vaccine, occurring at least 14days after the third dose. All adverse events (AEs) were collected for 30days following each dose. Serious AEs (SAEs) and intussusception cases were collected during the entire study. (ClinicalTrials.gov registry: NCT02062385). RESULTS: VE against RVGE of any-severity caused by any serotype was 69.3% (95% CI: 54.5, 79.7). The secondary efficacy analysis showed an efficacy of: 78.9% (95% CI: 59.1, 90.1) against severe RVGE caused by any serotype; 69.9% (95% CI: 55.2, 80.3) and 78.9% (95% CI: 59.1, 90.1) against any-severity and severe RVGE caused by serotypes contained in the vaccine, respectively. Within 30days following any vaccination, 53.5% (1079/2015) and 53.3% (1077/2019) of participants reported at least one AE, and 5.8% (116/2015) and 5.7% (116/2019) reported SAEs in the vaccine and placebo groups, respectively. No SAEs were considered vaccine-related in recipients of RV5. Two intussusception cases were reported in recipients of RV5 who recovered after receiving treatment. Neither was considered vaccine-related. CONCLUSIONS: In Chinese infants, RV5 was efficacious against any-severity and severe RVGE caused by any serotype and generally well-tolerated with respect to AEs.

Immunogenicity and safety of a trivalent inactivated influenza vaccine produced in Shenzhen, China.

A split-virion trivalent inactivated influenza vaccine produced according to the Chinese pharmacopeia (Shz-IIV3) has been commercially available in China since 2014. Here, we describe the results of a phase IV open-label trial to describe the immunogenicity and safety of the 2014-2015 Northern Hemisphere formulation of Shz-IIV3 in individuals ≥ 6 months of age. Subjects 6-35 months of age received 2 half-doses of Shz-IIV3 (0.25 ml) 28 d apart, and subjects ≥ 3 y of age received a single full dose (0.5 ml). The study included 602 subjects. Except for the A (H3N2) strain in subjects 3-17 years, geometric mean hemagglutination inhibition titer ratios were ≥ 10 and rates of seroconversion/significant increase in titer were ≥ 78% in all age groups. For the H3N2 strain in subjects 3-17 years, the geometric mean titer ratio was 3.8 and the rate of seroconversion/significant increase was 56%. Post-vaccination seroprotection rates were ≥ 88% for all strains in all age groups. The most common solicited reactions were injection-site pain/tenderness and fever, most of which were grade 1 and resolved within 3 d. Vaccine-related unsolicited adverse events were reported only by subjects 6-23 months, most of which were mild abnormal crying and irritability. No vaccine-related serious adverse events and no deaths were reported. No new safety signals or unexpected safety events occurred, although an immediate anaphylactic skin reaction occurred in one subject. This study confirmed that the 2014-2015 Northern Hemisphere formulation of Shz-IIV3 was well tolerated and highly immunogenic in subjects ≥ 6 months of age.

Immunogenicity and reactogenicity of the human rotavirus vaccine, RIX4414 oral suspension, when co-administered with routine childhood vaccines in Chinese infants.

This study evaluated the immunogenicity of the human rotavirus (RV) vaccine (RIX4414) when co-administered with routine childhood vaccines in Chinese infants (NCT01171963). Healthy infants aged 6-16 weeks received 2 doses of either RIX4414 or placebo according to a 0, 1-month schedule. Infants received routine diphtheria-tetanus-acellular pertussis (DTPa) and oral poliovirus (OPV) vaccines either separately from or concomitantly with RIX4414/placebo (separate and co-administration cohorts, respectively). Anti-RV IgA seroconversion rates (one month post-dose-2) and seropositivity rates (at one year of age) were measured using ELISA. Immune responses against the DTPa and OPV antigens were measured one month post-DTPa dose-3 in the co-administration cohort. Solicited local and general symptoms were recorded for 8-days post-vaccination (total cohort). The according-to-protocol immunogenicity population included 511 infants in the separate cohort and 275 in the co-administration cohort. One month post-RIX4414 dose-2, anti-RV IgA seroconversion rates were 74.7% (95% confidence interval [CI]: 68.9-79.9) and 64.2% (95% CI: 55.4-72.3) in the separate and co-administration cohorts; seropositivity rates at one year of age were 71.5% (95% CI: 65.5-77.1) and 50.0% (95% CI: 40.9-59.1), respectively. One month post-DTPa dose-3, all infants in the co-administration cohort were seroprotected against diphtheria and tetanus, and seropositive for pertussis toxoid, pertactin and filamentous haemaglutinin. Two months post-OPV dose-3, seroprotection rates against anti-poliovirus types 1, 2 and 3 were >99% in the co-administration cohort. Reactogenicity profiles were similar in both cohorts. RIX4414 was immunogenic and well-tolerated in Chinese infants and did not appear to interfere with the immunogenicity and reactogenicity of co-administered routine childhood vaccines.

Strategy vaccination against Hepatitis B in China.

Hepatitis B (HB) is a serious public health problem in China. Up to now, the hepatitis B virus (HBV) vaccination was the most cost-effective way to prevent HBV infection. Since 1992, when the Chinese government prioritized implementing the HBV vaccinations for newborns, China began to see a larger reduction in HBV infections. For children under 5 years, the prevalence of hepatitis B surface antigen (HBsAg) has decreased to 1.0%. However, many additional challenges for the prevention and control of HBV infection in China remain. There is a lack of knowledge of the significant impact of the HBV vaccination for the general public with 93 million HBV carriers and chronic HBV patients as infection sources. Therefore, the HBV vaccine application should focus on the optimization of immunization strategies according to HBV prevalence characteristics, improve the public's knowledge of HBV vaccinations, and help to ensure the protective effects of the HBV vaccine.

Human rotavirus vaccine (RIX4414) efficacy in the first two years of life: a randomized, placebo-controlled trial in China.

Rotaviruses (RV) are a major cause of severe gastroenteritis (GE) in children aged<5 y. For the first time in China, we assessed the efficacy of two oral doses of the human rotavirus vaccine (RIX4414) in infants during the first two years of life (113808/NCT01171963). Healthy infants aged 6-16 weeks were randomized (1:1) to receive two oral doses of either the RIX4414 vaccine/placebo according to a 0, 1 month schedule. Vaccine efficacy (VE) against severe RVGE was assessed from two weeks post-Dose 2 up until the end of the second RV season and calculated with its 95% confidence intervals (CI). The primary efficacy objective was met if the lower limit of the 95% CI on VE was ≥10%. Unsolicited symptoms reported during the 31-d post-vaccination follow-up period and serious adverse events (SAEs) reported throughout the study were assessed. Of 3333 enrolled infants, 3148 were included in the according-to-protocol efficacy cohort. Over two consecutive RV seasons, fewer severe RVGE episodes were reported in the RIX4414 group (n=21) vs. the placebo group (n=75). VE against severe RVGE was 72% (95% CI: 54.1-83.6); the lower limit of the 95% CI on VE was >10%. The number of unsolicited symptoms and SAEs reported was similar between both groups. Thirteen deaths (RIX4414=6; placebo=7) occurred during the study. All SAEs and deaths in the RIX4414 group were considered unrelated to vaccination. Two oral doses of RIX4414 vaccine provided a substantial level of protection against severe RVGE in Chinese children during the first two years of life.

Seroprevalence of hepatitis B and immune response to hepatitis B vaccination in Chinese college students mainly from the rural areas of western China and born before HBV vaccination integrated into expanded program of immunization.

The prevalence of hepatitis B surface antigen (HBsAg) in a population aged 15 y or older was high in China, but an immunization strategy for this population was unavailable. We investigated the seroprevalence of hepatitis B and immune response to HBV vaccine in Chinese college students (n=2040 participants), 11.1%, 80.8%, and 8.1% had confirmed, unknown and no HBV vaccination history, respectively. The seropositive rates for HBsAg, anti-HBs sole and anti-HBs plus anti-HBc were 12.6%, 25.7%, and 30.1%, respectively. The HBsAg seropositive rate was significantly lower in participants with confirmed HBV vaccination history than in those with unknown or no vaccination history (5.3%, 13.6%, and 12.6%, respectively, P=0.0019). The anti-HBs alone seropositive rate was significantly higher in participants with confirmed HBV vaccination history than in those with unknown or no vaccination history (37.6%, 25.3%, and 13.8%, respectively, P<0.0001). Participants negative for HBsAg, anti-HBs, and anti-HBc at baseline (n=600) were given three doses of recombinant HBV vaccine (GlaxoSmithKline) at month 0, 1, and 6. Robust immune response was elicited after two and three doses (seroprotective rate: 91.9% and 99.0%, respectively, and geometric mean concentration [GMC]: 95.8 and 742.6 IU/L, respectively). Fourteen months after the third dose, the anti-HBs seroprotective rate of the group remained more than 97%. The seroprotective rates and GMCs did not differ significantly by vaccination history. This study suggested that three doses of 20 µg HBV vaccine were needed for college students negative for HBsAg, anti-HBs, and anti-HBc to ensure high seroprotective rates and concentrations.

Reactogenicity and safety of a liquid human rotavirus vaccine (RIX4414) in healthy adults, children and infants in China: randomized, double-blind, placebo-controlled Phase I studies.

We report the findings of three randomized, double-blind, placebo-controlled Phase I studies undertaken to support licensure of the liquid formulation of the human G1P[8] rotavirus (RV) vaccine (RIX4414; GlaxoSmithKline Biologicals SA) in China. Healthy adults aged 18-45 y (n=48) and children aged 2-6 y (n=50) received a single dose of the human RV vaccine or placebo. Healthy infants (n=50) aged 6-16 weeks at the time of first vaccination received two oral doses of the human RV vaccine or placebo according to a 0, 1 mo schedule. In infants, blood samples were collected prior to vaccination and one month post-dose 2 to assess anti-RV IgA antibody concentrations using ELISA. Stool samples were collected from all infants on the day of each vaccination, at 7 and 15 d after each vaccination and one month post-dose 2. Stool samples were analyzed by ELISA for detection of RV antigen to assess RV antigen excretion. The reactogenicity profile of the human RV vaccine was found to be comparable to that of placebo in all age groups studied. The anti-RV IgA antibody seroconversion rate in infants after two vaccine doses was 86.7% (95% CI: 59.5-98.3). Vaccine take in infants who received the liquid human RV vaccine was 86.7% (95% CI: 59.5-98.3). A Phase III efficacy study of the human RV vaccine in the infant population in China has now been completed (ROTA-075/NCT01171963).

Dynamic change of mother-source neutralizing antibodies against enterovirus 71 and coxsackievirus A16 in infants.

BACKGROUND: Enterovirus 71 (EV71) and coxsackievirus A16 (Cox A16) are major causative agents for hand, foot and mouth disease (HFMD). Studies indicate that the frequent HFMD outbreaks result in a few hundreds children's death in China in recent years. The vaccine and other research for HFMD need to be developed urgently. THE AIMS OF OUR STUDY WERE: to explore dynamic development of mother-source neutralizing antibodies against EV71 and Cox A16 in infants from Jiangsu Province, China, and to provide the fundamental data for further establishing of corresponding immunization course. METHODS: Peripheral blood samples were collected from 133 of parturient women once immediately before delivery and their infants at two and seven months of age. Method of micro-dose cytopathogenic effect was used to measure neutralizing antibodies against EV71 and Cox A16, respectively. RESULTS: Seropositive rates of anti-EV71 and anti-Cox A16 in prenatal women were 79.7% (106/133) and 92.5% (123/133), respectively; geometric mean titers (GMTs) were 29.0 and 61.9; 75.9% (101/133) prenatal women were both positive in anti-EV71 and anti-Cox A16; seropositive rates of anti-EV71 and anti-Cox A16 were 25.6% (34/133) and 38.3% (51/133) in infants at two months of age; GMTs were 12.3 and 18.0, respectively. GMTs of anti-EV71 were significantly higher for infants at seven months (82.6) compared with that at two months (P < 0.05), showing infants had inapparently infected by EV71 during two to seven months. Although only one offspring (0.75%) at seven months was found having anti-Cox A16 transfered from maternal, this observation suggested no maternal antibody may remain in infants at seven months. CONCLUSIONS: The prevalence of EV71 and Cox A16 were relatively high in Jiangsu Province. Bivalent vaccine against both EV71 and Cox A16 should be developed, and the ideal time point for prime immunization for infants is around 2-5 months of age.

A novel immunostimulator, N-[alpha-O-benzyl-N-(acetylmuramyl)-L-alanyl-D-isoglutaminyl]-N6-trans-(m-nitrocinnamoyl)-L-lysine, and its adjuvancy on the hepatitis B surface antigen.

N(2)-[alpha-O-benzyl-N-(acetylmuramyl)-L-alanyl-D-isoglutaminyl]-N(6)-trans-(m-nitrocinnamoyl)-L-lysine (muramyl dipeptide C, or MDP-C) has been synthesized as a novel, nonspecific immunomodulator. The present study shows that MDP-C induces strong cytolytic activity by macrophages on P388 leukemia cells and cytotoxic activity by cytotoxic T lymphocytes (CTLs) on P815 mastocytoma cells. Our results also indicate that MDP-C is an effective stimulator for production of interleukin-2 and interleukin-12 by murine bone marrow derived dendritic cells (BMDCs) and production of interferon-gamma by CTLs. Additionally, MDP-C increases the expression levels of several surface molecules, including CD11c, MHC class I, and intercellular adhesion molecule-1 in BMDCs. Moreover, MDP-C remarkably enhances the immune system's responsiveness to hepatitis B surface antigen (HBsAg) in hepatitis B virus transgenic mice for both antibody production and specific HBsAg T-cell responses ex vivo. Our results indicate that MDP-C is an apyrogenic, nonallergenic, and low-toxicity immunostimulator with great potential for diagnostic, immunotherapeutic, and prophylactic applications in diseases such as hepatitis B and cancers.

Preparation and characterization of biodegradable microspheres containing hepatitis B surface antigen.

Poly-DL-lactide-poly(ethylene glycol) (PELA) microspheres containing Hepatitis B surface antigen (HBsAg) were elaborated by a solvent extraction method based on the formation of a double water/oil/water (w/o/w) emulsion. Microspheres were characterized in terms of morphology, size and size distribution, encapsulation efficiency, and the efficiency of microsphere formation (EMF). Transmission electron microscopy (TEM) and polyacrylamide gel electrophoresis (PAGE) were used to investigate the structural integrality of HBsAg encapsulated in PELA microspheres. The release profile was investigated by the measurement of antigen present in the release medium at various intervals. The PELA-10 microspheres displayed the highest antigen encapsulation efficiency (about 80%), and antigen molecules could be stabilized in the PELA-10 microspheres during the preparation process. It suggested that the PELA microspheres had a great potential as a new polymer adjuvant for HBsAg. The release of Hepatitis B surface antigen from poly-DL-lactide-poly(ethylene glycol) microspheres.

Poly-D,L-lactide-co-poly(ethylene glycol) microspheres as potential vaccine delivery systems.

Adjuvants aimed at increasing the immunogenicity of recombinant antigens remain a focus in vaccine development. Worldwide, there is currently considerable care for the development of biodegradable microspheres as controlled release of vaccines, since the major disadvantage of several currently available vaccines is the need for repeated administration. Microspheres prepared from the biodegradable and biocompatible polymers, the polylactide (PLA) or polylactide-co-glycolide (PLGA), have been shown to be effective adjuvants for a number of antigens. This review mainly focuses on polylactide-co-poly(ethylene glycol) (PELA) microspheres adjuvant as vaccine delivery systems by summarizing our and other research groups' investigation on properties of the microspheres formulation encapsulating several kinds of antigens. The results indicate that compared with the commonly used PLA and PLGA, PELA showed several potentials in vaccine delivery systems, which may be due to the block copolymer have its capability to provide a biomaterial having a broad range of amphiphilic structure. PELA microspheres can control the rate of release of entrapped antigens and therefore, offer potential for the development of single-dose vaccines. The PELA microspheres have shown great potential as a next generation adjuvant to replace or complement existing aluminum salts for vaccine potential. The review mainly aims to promote the investigation of PELA microspheres adjuvant for antigens for worldwide researcher.