Haiwen Tang

Safety and efficacy of human rotavirus vaccine during the first 2 years of life in Asian infants: Randomised, double-blind, controlled study

This study evaluates the safety and efficacy against severe rotavirus gastroenteritis of the oral live attenuated human rotavirus vaccine RIX4414 (Rotarix) during the first 2 years of life in Asian infants from high-income countries. Healthy infants were enrolled to receive 2 doses of RIX4414 (N=5,359) or placebo (N=5,349). From 2 weeks post-dose 2 to 2 years of age, vaccine efficacy was 96.1% (95%CI:85.1%; 99.5%) against severe rotavirus gastroenteritis, 100% (95%CI:80.8%; 100%) against wild-type G1P[8] and 93.6% (95%CI:74.7%; 99.3%) against circulating non-G1 rotavirus types. No intussusception cases were reported within 31 days post-vaccination. RIX4414 shows a good safety profile and offers high protection during the first 2 years of life with potentially significant public health impact in this population.

Immunogenicity and tolerability of an AS03A-adjuvanted prepandemic influenza vaccine: A phase III study in a large population of Asian adults

The immunogenicity and lot-to-lot consistency of an AS03-adjuvanted H5N1 vaccine were evaluated in 1206 Asian adults, randomised to receive two doses of adjuvanted (3.75 microg haemagglutinin) or diluent-mixed vaccines, 21 days apart. Post-Dose 2, 96.0% of vaccinees in the H5N1-AS03 group demonstrated a four-fold increase in neutralising antibody titres against the vaccine strain A/Vietnam/1194/2004 and 91.4% against strain A/Indonesia/05/2005. Haemagglutination-inhibiting antibodies (titre > or = 1:40) against A/Vietnam/1194/2004 and A/Indonesia/05/2005 strains were observed in 94.3% and 50.2% of subjects, respectively. Lot-to-lot consistency of the AS03-adjuvanted vaccine combinations was demonstrated. The AS03-adjuvanted vaccine was well tolerated, induced a high frequency of immune responses to the vaccine strain, allowed antigen sparing and promoted cross-clade immunity. These characteristics make it suitable for presumptive use if an H5N1 pandemic were considered to be imminent.

Rotavirus vaccine RIX4414 efficacy sustained during the third year of life: a randomized clinical trial in an Asian population.

RIX4414 (Rotarix™), has shown high efficacy during the first 2-years of life. A 2-year randomized, double-blind, placebo-controlled trial in Singapore, Hong Kong, and Taiwan was extended for another year. Infants (6-17 weeks) received 2-doses (1-2 months apart) of RIX4414 (n=5359) or placebo (n=5349). During the third-year follow-up, 4359 (RIX4414) and 4328 (placebo) infants were monitored. 64 (1.2%) and 2 (0.04%) infants in the placebo and RIX4414 groups, respectively, reported severe rotavirus-gastroenteritis (RVGE), resulting in a vaccine efficacy of 96.9% (95% CI [88.3-99.6]). Efficacy was 100% (67.5-100) in the third-year. RIX4414 was efficacious against G1 (100.0% [84.8-100]) and pooled non-G1 RV types (94.9% [80.2-99.4]). This study shows that the vaccine is highly efficacious, regardless of circulating RV-types, up to the first 3 years of life in affluent Asian urban populations.

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.

A new measles mumps rubella (MMR) vaccine: a randomized comparative trial for assessing the reactogenicity and immunogenicity of three consecutive production lots and comparison with a widely used MMR vaccine in measles primed children

OBJECTIVES A multicenter, single-blind, randomized, controlled clinical study was conducted in healthy 15-18-month-old children in order to assess the immunogenicity and reactogenicity of three consecutive lots of a new measles- mumps-rubella (MMR) vaccine, GSK MMR. DESIGN A total of 500 enrolled subjects were randomized into four groups to receive either a single dose of one of the three lots of GSK MMR (three groups--125 subjects in each group) or Merck MMR vaccine (125 subjects). Once clinical consistency had been demonstrated, the data were pooled and compared with the widely used Merck vaccine. Solicited local and general symptoms were recorded using diary cards, and antibody levels were determined using ELISA assays. RESULTS No differences in the incidence of local and general symptoms or seroconversion rates were seen in the groups receiving different lots of GSK MMR. Compared with Merck MMR, there was a significantly lower incidence of local pain (P<0.001) and swelling (P=0.038) in infants receiving the GSK MMR vaccine. The incidences of all other solicited local and general symptoms were comparable between the two groups. No signs of suspected meningitis were reported. No serious adverse events were reported by the investigator to be related to vaccination. Equivalent seroconversion rates and postvaccination GMTs were observed in the groups receiving the two MMR vaccines. In conclusion, the new GSK MMR vaccine administered in measles-primed children demonstrated satisfactory immunogenicity and safety profiles as good as the Merck MMR vaccine.

Efficacy, safety and immunogenicity of a human rotavirus vaccine (RIX4414) in Hong Kong children up to three years of age: A randomized, controlled trial

BACKGROUND A phase III, double-blind, randomized, controlled trial was conducted in Hong Kong to evaluate the efficacy, safety and immunogenicity of a human rotavirus vaccine, RIX4414 (Rotarix) against severe rotavirus gastroenteritis in children up to three years of age. METHODS Healthy infants aged 6-12 weeks were enrolled between 08-December-2003 and 31-August-2005 and received two oral doses of either RIX4414 vaccine (N=1513) or placebo (N=1512) given 2 months apart. Vaccine efficacy was assessed from two weeks post-Dose 2 until the children were two and three years of age. Anti-rotavirus IgA seroconversion rate was calculated pre-vaccination and 1-2 months post-Dose 2 using ELISA (cut-off=20 U/mL) for 100 infants. Safety was assessed until the children were two years of age; serious adverse events (SAEs) were recorded throughout the study period. RESULTS In children aged two and three years of life, vaccine efficacy against severe rotavirus gastroenteritis was 95.6% (95% CI: 73.1%-99.9%) and 96.1% (95% CI: 76.5%-99.9%), respectively. The seroconversion rate 1-2 months after the second dose of RIX4414 was 97.5% (95% CI: 86.8%-99.9%). At least one SAE was recorded in 439 and 477 infants who were administered RIX4414 and placebo, respectively (p-value=0.130). Six intussusception cases were reported (RIX4414=4; placebo=2) and none was assessed to be vaccine-related. CONCLUSION RIX4414 was efficacious, immunogenic and safe in the prevention of rotavirus gastroenteritis for at least two years post-vaccination in Hong Kong children.

Immunogenicity and safety of 10-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) co-administered with routine childhood vaccines in Taiwan

BACKGROUND/PURPOSE The immunogenicity and safety of the 10-valent pneumococcal nontypeable Haemophilus influenzae (H. Influenzae) protein D conjugate vaccine (PHiD-CV), co-administered with routine childhood vaccines, were assessed in Taiwanese infants. METHODS In this open study, 230 healthy infants were primed with three doses of PHiD-CV (Synflorix) and diphtheria, tetanus, acellular pertussis, hepatitis B (HBV), inactivated poliomyelitis and Haemophilus influenzae type b (Hib) conjugate vaccine (DTPa-HBV-IPV/Hib vaccine) at 1.5, 3 and 6 months of age and two doses of oral human rotavirus vaccine at 1.5 and 3 months. Pneumococcal immune responses were assessed 1 month post-dose three, by 22F-inhibition ELISA and opsonophagocytic activity (OPA) assay. Local and general solicited/unsolicited symptoms and serious adverse events (SAEs) were recorded. RESULTS At least 95.4% of participants had an antibody concentration ≥ 0.2 μg/mL against each vaccine serotype. At least 96.1% of participants had an OPA titer ≥ 8 against each vaccine serotype except 6B (87.3%). All infants, but one, were seropositive for antibodies against nontypeable H. influenzae protein D. Immune responses to the co-administered vaccines were good and in line with previous reports. PHiD-CV was well tolerated, with low (≤ 6.3%) incidences of grade 3 solicited local symptoms. The frequencies of general symptoms were in line with other pneumococcal conjugate vaccine studies. There were no systematic increases in incidences of solicited general or local symptoms with successive doses. There were no reports of grade 3 fever (rectal temperature > 40 °C) or SAEs considered to be causally related to vaccination. CONCLUSION PHiD-CV co-administered with routine childhood vaccines within the first 6 months of life, was highly immunogenic, and well tolerated in Taiwanese infants.

Booster vaccination against pertussis in Chinese children at six years of age using reduced antigen content diphtheria-tetanus-acellular pertussis vaccine (Boostrix™)

Pertussis continues to circulate in Chinese communities and older children, adolescents and adults are sources of infection for unprotected infants. Two studies conducted in Jiangsu Province in the People’s Republic of China assessed the immunogenicity, reactogenicity and safety of Boostrix™, a combined reduced antigen content diphtheria-tetanus-acellular pertussis vaccine (dTpa) when administered as a booster dose to children 6−8 years of age. Immunogenicity was assessed before and one month after vaccination in a subset. Reactogenicity was assessed over a 4-day follow-up using diary cards. A total of 690 Chinese subjects were enrolled. Boostrix™ was well tolerated. One month after the booster dose, 100% of dTpa recipients had seroprotective antibody concentrations against diphtheria and tetanus. The percentage of subjects with a response against pertussis antigens (using locally defined cut-offs) was 91.9% for pertussis toxoid, 98.8% for filamentous hemagglutinin, and 100% for pertactin. The exploratory analysis showed no statistically significant differences between dTpa or diphtheria-tetanus vaccine in terms of the percentage of subjects with seroprotective antibodies against diphtheria or tetanus. These studies demonstrate that Boostrix™ is well tolerated and immunogenic when administered as a booster dose to 6−8 year old Chinese children previously immunized with a combined diphtheria-tetanus-pertussis vaccine. Introduction of dTpa into the routine Chinese immunization schedule would provide booster vaccination against pertussis without the addition of further injections into the Chinese vaccination schedule and is likely to promote improved pertussis control in older children.

Efficacy, immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine in Chinese women aged 18–25 years: event-triggered analysis of a randomized controlled trial

We previously reported the results of a phase II/III, double‐blind, randomized controlled study in Chinese women (NCT00779766) showing a 94.2% (95% confidence interval: 62.7–99.9) HPV‐16/18 AS04‐adjuvanted vaccine efficacy (VE) against cervical intraepithelial neoplasia grade 1 or higher (CIN1+) and/or 6‐month (M) persistent infection (PI) with a mean follow‐up of <2 years, and immunogenicity until 7 months post‐dose 1. Here, we report efficacy and safety results from an event‐triggered analysis with ~3 years longer follow‐up, and immunogenicity until M24. Healthy 18–25‐year‐old women (N = 6051) were randomized (1:1) to receive three doses of HPV‐16/18 vaccine or Al(OH)3 (control) at M0, 1, 6. VE against HPV‐16/18‐associated CIN2+, and cross‐protective VE against infections with nonvaccine oncogenic HPV types, immunogenicity, and safety were assessed. In the according‐to‐protocol efficacy cohort, in initially seronegative/DNA‐negative women (vaccine group: N = 2524; control group: N = 2535), VE against HPV‐16/18‐associated CIN2+ was 87.3% (5.3–99.7); VE against incident infection or against 6‐month persistent infection associated with HPV‐31/33/45 was 50.1% (34.3–62.3) or 52.6% (24.5–70.9), respectively. At least, 99.6% of HPV‐16/18‐vaccines remained seropositive for anti‐HPV‐16/18 antibodies; anti‐HPV‐16 and ‐18 geometric mean titers were 1271.1 EU/mL (1135.8–1422.6) and 710.0 EU/ml (628.6–801.9), respectively. Serious adverse events were infrequent (1.7% vaccine group [N = 3026]; 2.5% control group [N = 3026]). Of the 1595 reported pregnancies, nine had congenital anomalies (five live infants, three elective terminations, one stillbirth) that were unlikely vaccination‐related (blinded data). VE against HPV‐16/18‐associated CIN2+ was demonstrated and evidence of cross‐protective VE against oncogenic HPV types was shown. The vaccine was immunogenic and had an acceptable safety profile.

Immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine in healthy Chinese girls and women aged 9 to 45 years.

Immunogenicity and safety of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine were evaluated in healthy Chinese females aged 9–45 years in 2 phase IIIB, randomized, controlled trials. Girls aged 9–17 years (ClinicalTrials.gov, NCT00996125) received vaccine (n = 374) or control (n = 376) and women aged 26–45 years (NCT01277042) received vaccine (n = 606) or control (n = 606) at months 0, 1, and 6. The primary objective was to show non-inferiority of anti-HPV-16 and -18 immune responses in initially seronegative subjects at month 7, compared with Chinese women aged 18–25 years enrolled in a separate phase II/III trial (NCT00779766). Secondary objectives were to describe the anti-HPV-16 and -18 immune response, reactogenicity and safety. At month 7, immune responses were non-inferior for girls (9–17 years) vs. young women (18–25 years): the upper limit of the 95% confidence interval (CI) for the geometric mean titer (GMT) ratio (women/girls) was below the limit of 2 for both anti-HPV-16 (0.37 [95% CI: 0.32, 0.43]) and anti-HPV-18 (0.42 [0.36, 0.49]). Immune responses at month 7 were also non-inferior for 26–45 year-old women vs. 18–25 year-old women: the upper limit of the 95% CI for the difference in seroconversion (18–25 minus 26–45) was below the limit of 5% for both anti-HPV-16 (0.00% [–1.53, 1.10]) and anti-HPV-18 (0.21% [–1.36, 1.68]). GMTs were 2- to 3-fold higher in girls (9–17 years) as compared with young women (18–25 years). The HPV-16/18 AS04-adjuvanted vaccine had an acceptable safety profile when administered to healthy Chinese females aged 9–45 years.