[Show abstract][Hide abstract] ABSTRACT: Evaluation of immunogenicity and safety of a 2-dose liquid formulation of human rotavirus vaccine, RIX4414 following WHO's Expanded Program on Immunization (EPI) schedule (0, 1, and 2 months; Month 0 indicates day of enrollment) in Vietnam and the Philippines. Infants aged 6-10 (mean=8.7 ± 1.07 weeks Vietnam) and 5-10 weeks (mean=6.6 ± 1.03 weeks Philippines) received two doses of RIX4414 vaccine (V) and one dose of placebo (PL) or three placebo doses concomitantly with commercially available diphtheria-tetanus-whole-cell pertussis, hepatitis B and oral poliovirus vaccines. The vaccination schedules were: V-V-PL, V-PL-V and PL-PL-PL (Vietnam); PL-V-V, V-PL-V and PL-PL-PL (Philippines). Anti-rotavirus seroconversion rate was assessed pre-vaccination and post-vaccination (ELISA cut-off=20 U/ml). 375 infants were enrolled in each country. Seroconversion rates at one month post-Dose 2 of RIX4414 were Vietnam 63.3% (95% CI: 54.3-71.6) in V-V-PL group and 81.5% (95% CI: 73.4-88) in V-PL-V group; Philippines 70% (95% CI: 61-78) in PL-V-V group and 59.2% (95% CI: 49.8-68) in V-PL-V group. Frequencies of solicited (8-day post-each dose) and unsolicited symptoms (31-day post-each dose) were similar. Two-doses of rotavirus vaccine administered within the WHO EPI offer flexibility in existing schedule, though both schedules provides good immune responses.
[Show abstract][Hide abstract] ABSTRACT: The lyophilized formulation of a human rotavirus vaccine, Rotarix™ (RIX4414) is highly immunogenic. In order to comply with the World Health Organization's (WHO) recommendation, a liquid formulation of the vaccine that does not require reconstitution was developed. The immunogenicity, reactogenicity and safety of the liquid formulation were compared with lyophilized formulation in two Finnish studies. In Study A infants aged 6-12 weeks received two doses of the lyophilized or liquid formulation of the vaccine or placebo following a 0,1 month schedule. In Study B, infants aged 10-17 weeks received two doses of either liquid or lyophilized formulation of the vaccine. In both studies, anti-rotavirus IgA antibodies were assessed pre-vaccination and one month post-Dose 2. In Study A, the anti-rotavirus seroconversion rate was 90% (95% CI: 81.2-95.6%) and 83.7% (95% CI: 74.2-90.8%) in the groups that received the liquid and the lyophilized formulation of RIX4414, respectively; the respective anti-rotavirus IgA seroconversion rates in Study B were 88.6% (95% CI: 86.1-90.8%) and 90.5% (95% CI: 86.2-93.8%). Reactogenicity and safety profiles of the two vaccine formulations were similar. Liquid formulation of the rotavirus vaccine allows greater flexibility in supply and reduces logistical costs.
[Show abstract][Hide abstract] ABSTRACT: This study assessed the immunogenicity and reactogenicity of a live-attenuated varicella vaccine (Oka strain), Varilrix in Indonesian children age 10 months to 12 years. A total of 300 seronegative subjects were stratified into three age subgroups (10 months to < 3 years, 3 years to < 7 years and 7 to 12 years) and all received a single-dose of Oka strain varicella vaccine. One solicited local symptom (injection site soreness) was reported during the 43-day post-vaccination follow-up period. Fever (29/295; 10%) was more prevalent than rash (3/295; 1%) but the incidence of grade 3 fever (defined as axillary temperature of >39 degrees C) was infrequent. No grade 3 unsolicited events and no serious adverse events were reported. The vaccine proved to be immunogenic in all age groups; all but one subject seroconverted for anti-varicella antibodies 43-days post-vaccination. This study demonstrated that the live-attenuated varicella vaccine (Oka strain) was well tolerated and immunogenic with no safety issues when administered as a single dose primary vaccination to healthy, seronegative Indonesian subjects age 10 months to 12 years.
Full-text · Article · Sep 2009 · The Southeast Asian journal of tropical medicine and public health
[Show abstract][Hide abstract] ABSTRACT: 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 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.
[Show abstract][Hide abstract] ABSTRACT: To assess immunogenicity, antibody persistence, immune memory, and reactogenicity of a novel heptavalent DTPw-HBV/Hib-MenAC (diphtheria, tetanus, whole cell pertussis-hepatitis B virus/Haemophilus influenzae type b-Neisseria meningitidis serogroups A and C) vaccine.
This was an open, randomized study in the Philippines, with DTPw-HBV/Hib-MenAC administered at 6, 10, and 14 weeks of age. Three different polysaccharide contents of the conjugate vaccine components were assessed with conjugated PRP (polyribosylribitol phosphate), MenA, and MenC polysaccharides at the following doses: 2.5 microg of each, 5 microg of each, or 2.5 microg of PRP and 5 microg each of MenA and MenC. Controls received licensed DTPw-HBV and Hib or DTPw-HBV/Hib and MenC conjugate vaccines separately. Immune memory was evaluated via plain polysaccharide challenge administered to half of the subjects at 10 months of age.
After primary vaccination, at least 97.7% of DTPw-HBV/Hib-MenAC recipients had serum bactericidal antibody (SBA)-MenA and SBA-MenC titers > or =1:8, and at least 99% had anti-PRP antibody concentrations > or =0.15 microg/ml. Immune responses to DTPw-HBV components were not impaired by the lowest dose of Hib-MenAC vaccine. Plain polysaccharide challenge induced marked increases in Hib, MenA, and MenC antibodies in primed subjects, indicative of immune memory. All of the experimental vaccines were well tolerated.
The lowest dose of DTPw-HBV/Hib-MenAC polysaccharide conjugate vaccine was well tolerated, immunogenic, had good persistence of antibodies, and demonstrated immune memory, and consequently was selected for further development.
Preview · Article · May 2008 · International Journal of Infectious Diseases
[Show abstract][Hide abstract] ABSTRACT: Background: RIX4414(Rotarix, a trademark of GlaxoSmithKline), an oral live attenuated human rotavirus (RV) vaccine has previously been shown to be highly effective against RV gastroenteritis(GE). The efficacy evaluation of RIX4414 administered concomitantly with routine EPI vaccinations including Oral Polio Vaccine(OPV) to healthy infants in a phase III, double-blind, randomized, placebo-controlled and multi-center study
(444563/024/NCT00139347) conducted in six countries in Latin-America is presented.Methods: Healthy infants
aged 6-12 weeks were enrolled to receive two doses of RIX4414(N = 4376) or placebo(N = 2192) according to a 0,1—2 month schedule, administered concomitantly with Dose 1 and Dose 2 of routine pediatric vaccines including OPV, given respecting the national immunisation guidelines.Vaccine efficacy(VE) was calculated from two weeks post-Dose2 until one year of age. Severe GE was defined as an episode of diarrhea requiring hospitalization and/or re-hydration therapy in a medical facility. Diarrhoeal samples were analyzed for RV by ELISA and typed by RT-PCR based method. Safety data were collected throughout the study.
Results: During the efficacy follow-up period (mean duration of 7.4 months) RIX4414 has offered 81.6%
(95%CI:54.4;93.5) protection against severe RVGE and 88.3% (95%CI:64.0;97.1) against hospitalization due to RVGE. For severe RVGE, VE against wild-type G1 was 100% (95%CI:<0;100) and 80.6% (95%CI:51.4;93.2) against pooled non-G1 RV types (G2,G9). No clinically meaningful difference between RIX4414 group and the placebo group for serious adverse events were reported.
Conclusion: Two doses of RIX4414(RotarixTM)offer high protection against severe RVGE and related hospitalizations when co-administered with specific childhood vaccines including OPV. These results show that co-administration with OPV does not impact the efficacy of RotarixTM and are in line with the high efficacy against severe RVGE of 85% demonstrated in a large Phase III Latin America study with staggered co-administration of OPV. This finding is of significance for the implementation of RV vaccination programmes
in many countries where OPV is still routinely administered.
[Show abstract][Hide abstract] ABSTRACT: Background: The GlaxoSmithKline, oral live-attenuated human rotavirus vaccine RIX4414 RotarixTM) was shown to be highly immunogenic. A phase III, randomized, double-blind, placebo-controlled study(NCT00139347-e-Track444563) was conducted in Latin America to assess the effect of RotarixTM
on the immunogenicity of co-administered oral polio vaccine( OPV).
Methods: 6568 healthy infants aged 6—12 weeks were enrolled to receive two doses of RIX4414 (RIX4414-OPV group:N = 4376) or placebo (Placebo-OPV:N = 2192) according to a 0,1—2 month schedule, administered concomitantly with Dose1 and Dose2 of routine vaccines including oral poliovirus vaccines (OPV), according to recommended local national immunization guidelines. For the immunogenicity subset for OPV (N = 900) seroprotection rates for anti-polio types1,2,3 antibodies were determined at 1 month post-
Dose3 of routine pediatric vaccination(virus neutralization assay, cut-off≥8ED50). Of these, a subset of infants received an additional OPV dose at birth.
Results: No significant difference in anti-polio1,2,3 seroprotection rates was observed at 1 month post-Dose3 of OPV between RIX4414-OPV and Placebo-OPV groups.
Conclusions: Co-administration of RotarixTM with OPV does not interfere with the immune response to OPV. This is of importance in considering the inclusion of RV vaccination into UMV programs in countries where OPV is still used.
[Show abstract][Hide abstract] ABSTRACT: We aimed to assess the efficacy of the oral live attenuated human rotavirus vaccine Rotarix (RIX4414) for prevention of rotavirus gastroenteritis in European infants during their first 2 years of life.
3994 study participants were enrolled from six countries and were randomly assigned two oral doses of either RIX4414 (n=2646) or placebo (n=1348), which were coadministered with the first two doses of specific childhood vaccinations. Follow-up for gastroenteritis episodes was undertaken from 2 weeks post-dose two through the two consecutive rotavirus seasons following vaccinations (combined efficacy follow-up period; mean duration 17 months [SD 1.6]). Our primary endpoint was vaccine efficacy against rotavirus gastroenteritis of any severity during the first efficacy follow-up period (2 weeks post-dose two to the end of the first rotavirus season). Stool specimens obtained during gastroenteritis episodes were tested for rotavirus by ELISA and typed by RT-PCR. Episodes scoring 11 or greater on the 20-point Vesikari scale were classified as severe. Analysis was according to protocol. This study is registered with ClinicalTrials.gov, number NCT00140686 (eTrack102247).
120 infants were excluded from the according-to-protocol analysis. During the first efficacy follow-up period (mean duration 5.7 months [SD 1.2]), 24 of 2572 infants allocated RIX4414 versus 94 of 1302 given placebo had rotavirus gastroenteritis episodes of any severity, resulting in a vaccine efficacy of 87.1% (95% CI 79.6-92.1; p<0.0001). For the combined efficacy follow-up period, vaccine efficacy against severe rotavirus gastroenteritis was 90.4% (85.1-94.1; p<0.0001), for admission owing to rotavirus gastroenteritis 96.0% (83.8-99.5; p<0.0001), and for rotavirus-related medical attention 83.8% (76.8-88.9; p<0.0001), and significant protection against severe rotavirus gastroenteritis by circulating G1, G2, G3, G4, and G9 rotavirus types was shown.
In a European setting, two doses of RIX4414 coadministered with childhood vaccines provided high protection against any and severe rotavirus gastroenteritis, with an overall reduction of admissions for gastroenteritis over two consecutive rotavirus epidemic seasons.
[Show abstract][Hide abstract] ABSTRACT: This open, randomized, controlled study [208136/018] assessed the safety and immunogenicity of early vaccination with an experimental tetravalent measles-mumps-rubella-varicella (MMRV) vaccine (GlaxoSmithKline Biologicals) compared to concomitant administration of separate licensed MMR (Priorix) and varicella (Varilrix) vaccines (MMR+V).
Vaccines were administered as a two-dose course in healthy children at 9 and 12 months of age (N = 153 in the MMRV group and N = 146 in the MMR+V group).
The incidence of fever of any intensity (axillary temperature > or = 37.5 degrees C) during the 15 days of follow-up post-dose 1 was higher in the MMRV group than in the MMR+V group (48.3% vs 25.7%, respectively) but was low in both groups post-dose 2 (20.3% and 22.1%, respectively). The incidence of fever > 39.0 degrees C and the incidence of solicited local symptoms (pain, redness, swelling) were low ( < or = 5.3% and < or = 13.7%, respectively) in the two groups after each vaccine dose. Seroconversion rates were similar in the two groups for all vaccine antigens after each vaccine dose and were > or = 99.2% for each antigen post-dose 2. Anti-measles GMT was higher in the MMRV group than in the MMR+V group after the first vaccine dose. After the second dose, slight to moderate increases in measles, mumps and rubella antibody titers and a substantial increase in varicella antibody titer were seen in both groups, leading to higher GMTs in the MMRV group compared with the MMR+V group for measles, mumps and varicella. Anti-rubella antibody GMTs were similar in the two groups post-dose 2.
Early vaccination with two doses of this experimental MMRV vaccine at 9 and 12 months of age was well-tolerated and at least as immunogenic as two doses of separate licensed MMR and varicella vaccines.
[Show abstract][Hide abstract] ABSTRACT: In Singapore, we conducted a phase II randomized, double-blind, placebo-controlled dose ranging study using an attenuated human rotavirus vaccine, RIX4414. Altogether, 2464 healthy infants were recruited. Two oral doses of vaccine at 104.7, 105.2 or 106.1 ffu or placebo were administered with routine immunizations at 3 and 4 months of age. Seroconversion and 'vaccine take' in the vaccine groups 1-month post dose 2 varied from 76 to 91% and 98 to 100% respectively. Vaccine was well tolerated and did not interfere with response of concomitantly administered vaccines.
[Show abstract][Hide abstract] ABSTRACT: Older children and adults, susceptible to pertussis because of waning immunity, may serve as a reservoir of infection, leading to severe disease among young unvaccinated infants. Booster diphtheria-tetanus-acellular pertussis (dTpa) vaccination in older age groups is rare in Singapore, one reason being the increase in reactogenicity with each successive dose. The aim of this study was to assess the immunogenicity, safety and reactogenicity of a reduced antigen, combined dTpa vaccine as a single booster dose in healthy adults aged 18 years or older.
A total of 150 healthy adults, 18 to 60 years of age, received a single dose of GlaxoSmithKline Biologicals' dTpa vaccine with reduced content for diphtheria and pertussis, with measurement of pre- and post-vaccination antibody titres.
Prior to vaccination, 71.6 percent and 92.6 percent of the subjects had anti-diphtheria and anti-tetanus antibody levels greater than or equal to 0.1 IU/mL, respectively. 46.7 percent, 98.5 percent and 44.4 percent of subjects were seropositive for pertussis toxin (PT), filamentous haemagglutinin (FHA) and pertactin (PRN) antibodies, respectively. One month after vaccination, there was an increase in geometric mean titres from pre-vaccination to post-vaccination blood samples for anti-diphtheria (greater than seven-fold), anti-tetanus (greater than five-fold), anti-PT (greater than 11-fold), anti- FHA (greater than 25-fold) and anti-PRN (greater than 31-fold) antibodies. Solicited grade three local symptoms (pain, redness and swelling) were reported in 14.1 percent, 8.1 percent and 10.4 percent of subjects, respectively. No serious adverse events were reported.
In summary, the dTpa vaccine is immunogenic, safe and well-tolerated in Singaporean adults.
Full-text · Article · May 2006 · Singapore medical journal
[Show abstract][Hide abstract] ABSTRACT: Severe rotavirus gastroenteritis in children causes significant morbidity worldwide and substantial deaths in developing countries. Hence, a live attenuated vaccine Rotarix was developed with human strain RIX4414 of G1P1A P specificity. RIX4414 trials in infants have begun in developed and developing countries worldwide. An overview of RIX4414 in developed and developing countries and prospects with this vaccine in Asia are presented.
Completed RIX4414 trials have been reviewed.
Two oral doses of RIX4414 were well tolerated with a reactogenicity profile similar to placebo. RIX4414 was also highly immunogenic, e.g., in a dose-ranging study conducted in Singapore, 98.8% to 100% of infants had a vaccine take after 2 doses. RIX4414 did not affect the immune response of simultaneously administered routine infant vaccines. RIX4414 significantly reduced severe rotavirus gastroenteritis in settings where multiple serotypes including the emerging G9 type co-circulated.
These encouraging results warrant further evaluation of the vaccine worldwide and especially in developing countries with the highest need. Therefore, evaluation of the Rotarix vaccine is continuing in large phase III trials in Asia and worldwide.
Full-text · Article · Jan 2006 · Annals of the Academy of Medicine, Singapore
[Show abstract][Hide abstract] ABSTRACT: An open, randomized study evaluated the immune response and safety of two different regimens of diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b (DTPa-HBV-IPV-Hib) immunization in infants primed at birth with hepatitis B vaccine. One-half of the 150 healthy, full-term infants received a DTPa HBV-IPV-Hib vaccine at 1 1/2, 3 and 5 months of age; the other received a DTPa-IPV-Hib vaccine at 1 1/2, 3 and 5 months of age with separate HBV vaccine at 1 and 5 months of age. Immune response was similar following the two regimens with 100% of the vaccinees seroprotected for HBV, diphtheria, tetanus, Hib and poliovirus types 2 and 3 diseases after the full vaccination course. One vaccinee in the DTPa HBV-HPV- Hib group failed to respond to the poliovirus type 1 antigen. Response to the three pertussis antigens ranged from 92-97% in the DTPa-IPV-Hib plus separate HBV group and 100% in the DTPa HBV-IPV-Hib group. The most frequently reported post-vaccination symptoms were irritability in the DTPa-IPV-Hib plus separate HBV group (49% of vaccinees) and fever, defined as axillary temperature > or =37.5 degrees C, in the DTPa HBV- IPV-Hib group (50% of vaccinees).
Preview · Article · Oct 2004 · The Southeast Asian journal of tropical medicine and public health