Angkool Kerdpanich

Relative Efficacy of AS03-Adjuvanted Pandemic Influenza A(H1N1) Vaccine in Children: Results of a Controlled, Randomized Efficacy Trial

Abstract Background. The vaccine efficacy (VE) of 1 or 2 doses of AS03-adjuvanted influenza A(H1N1) vaccine relative to that of 2 doses of nonadjuvanted influenza A(H1N1) vaccine in children 6 months to <10 years of age in a multinational study conducted during 2010–2011. Methods. A total of 6145 children were randomly assigned at a ratio of 1:1:1 to receive 2 injections 21 days apart of A/California/7/2009(H1N1)-AS03 vaccine at dose 1 and saline placebo at dose 2, 2 doses 21 days apart of A/California/7/2009(H1N1)-AS03 vaccine (the Ad2 group), or 2 doses 21 days apart of nonadjuvanted A/California/7/2009(H1N1) vaccine (the NAd2 group). Active surveillance for influenza-like illnesses continued from days 14 to 385. Nose and throat samples obtained during influenza-like illnesses were tested for A/California/7/2009(H1N1), using reverse-transcriptase polymerase chain reaction. Immunogenicity, reactogenicity, and safety were assessed. Results. There were 23 cases of confirmed 2009 pandemic influenza A(H1N1) (A[H1N1]pdm09) infection for the primary relative VE analysis. The VE in the Ad2 group relative to that in the NAd2 group was 76.8% (95% confidence interval, 18.5%–93.4%). The benefit of the AS03 adjuvant was demonstrated in terms of the greater immunogenicity observed in the Ad2 group, compared with the NAd2 group. Conclusion. The 4–8-fold antigen-sparing adjuvanted pandemic influenza vaccine demonstrated superior and clinically important prevention of A(H1N1)pdm09 infection, compared with nonadjuvanted vaccine, with no observed increase in medically attended or serious adverse events. These data support the use of adjuvanted influenza vaccines during influenza pandemics. Clinical Trials Registration. NCT01051661.

Prevalence and Incidence of Respiratory Syncytial Virus and Other Respiratory Viral Infections in Children Aged 6 Months to 10 Years With Influenza-like Illness Enrolled in a Randomized Trial

In children aged 6 months to <10 years, the incidence of influenza-like illness associated with respiratory syncytial virus was 7.0 per 100 person-years. The highest burden occurred in older infants and children, which may inform vaccination strategies.

Safety and Immunogenicity of a Rederived, Live-Attenuated Dengue Virus Vaccine in Healthy Adults Living in Thailand: A Randomized Trial

Safety and immunogenicity of two formulations of a live-attenuated tetravalent dengue virus (TDEN) vaccine produced using rederived master seeds from a precursor vaccine were tested against a placebo control in a phase II, randomized, double blind trial (NCT00370682). Two doses were administered 6 months apart to 120 healthy, predominantly flavivirus-primed adults (87.5% and 97.5% in the two vaccine groups and 92.5% in the placebo group). Symptoms and signs reported after vaccination were mild to moderate and transient. There were no vaccine-related serious adverse events or dengue cases reported. Asymptomatic, low-level viremia (dengue virus type 2 [DENV-2], DENV-3, or DENV-4) was detected in 5 of 80 vaccine recipients. One placebo recipient developed a subclinical natural DENV-1 infection. All flavivirus-unprimed subjects and at least 97.1% of flavivirus-primed subjects were seropositive to antibodies against all four DENV types 1 and 3 months post-TDEN dose 2. The TDEN vaccine was immunogenic with an acceptable safety profile in flavivirus-primed adults.

Respiratory viruses and influenza-like illness: Epidemiology and outcomes in children aged 6 months to 10 years in a multi-country population sample

Summary Background Better population data on respiratory viruses in children in tropical and southern hemisphere countries is needed. Methods The epidemiology of respiratory viruses among healthy children (6 months to <10 years) with influenza-like illness (ILI) was determined in a population sample derived from an influenza vaccine trial (NCT01051661) in 17 centers in eight countries (Australia, South East Asia and Latin America). Active surveillance for ILI was conducted for approximately 1 year (between February 2010 and August 2011), with PCR analysis of nasal and throat swabs. Results 6266 children were included, of whom 2421 experienced 3717 ILI episodes. Rhinovirus/enterovirus had the highest prevalence (41.5%), followed by influenza (15.8%), adenovirus (9.8%), parainfluenza and respiratory syncytial virus (RSV) (both 9.7%), coronavirus (5.6%), human metapneumovirus (5.5%) and human bocavirus (HBov) (2.0%). Corresponding incidence per 100 person-years was 29.78, 11.34, 7.03, 6.96, 6.94, 4.00, 3.98 and 1.41. Except for influenza, respiratory virus prevalence declined with age. The incidence of medically-attended ILI associated with viral infection ranged from 1.03 (HBov) to 23.69 (rhinovirus/enterovirus). The percentage of children missing school or daycare ranged from 21.4% (HBov) to 52.1% (influenza). Conclusions Active surveillance of healthy children provided evidence of respiratory illness burden associated with several viruses, with a substantial burden in older children.

A randomized controlled study to evaluate the immunogenicity of a trivalent inactivated seasonal influenza vaccine at two dosages in children 6 to 35 months of age

The trivalent inactivated influenza vaccine Fluarix™ is licensed in the US for adults and children from 3 years old. This randomized observer-blind study (NCT00764790) evaluated Fluarix™ at two doses; 0.25 ml (Flu-25) and 0.5 ml (Flu-50) in children aged 6–35 months. The primary objective was to demonstrate immunogenic non-inferiority vs. a control vaccine (Fluzone®; 0.25 ml). Children received Flu-25 (n = 1107), Flu-50 (n = 1106) or control vaccine (n = 1104) at Day 0 and for un-primed children, also on Day 28. Serum hemagglutination-inhibition titers were determined pre-vaccination and at Day 28 (primed) or Day 56 (un-primed). Non-inferiority was assessed by post-vaccination geometric mean titer (GMT) ratio, (upper 95% confidence interval [CI] ≤ 1.5) and difference in seroconversion rate (upper 95% CI ≤ 10%). Reactogenicity/safety was monitored. The immune response to Flu-50 met all regulatory criteria. Indicated by adjusted GMT ratios [with 95% CI], the criteria for non-inferiority of Flu-50 vs. control vaccine were reached for the B/Florida strain (1.13 [1.01–1.25]) but not for the A/Brisbane/H1N1 (1.74 [1.54–1.98]) or A/Uruguay/H3N2 (1.72 [1.57–1.89]) strains. In children aged 18–35 months similar immune responses were observed for Flu-50 and the control vaccine. Flu-50 induced a higher response than Flu-25 for all strains. Temperature (≥ 37.5°C) was reported in 6.2%, 6.4%, and 6.6% of the Flu-25, Flu-50, and control group, respectively. Reactogenicity/safety endpoints were within the same range for all vaccines. In children aged 6–35 months, immune responses with Flu-50 fulfilled regulatory criteria but did not meet the pre-defined criteria for non-inferiority vs. control. This appeared to be due to differences in immunogenicity in children aged < 18 months.

Immunogenicity of a live-attenuated human rotavirus RIX4414 vaccine with or without buffering agent

Aim: The lyophilized form of the human rotavirus RIX4414 vaccine (Rotarix™) is usually reconstituted with a liquid calcium carbonate (CaCO3) buffer and administered orally. However, errors in the reconstitution could occur (e.g. reconstituted with water instead of CaCO3 buffer) or the buffer might be temporarily unavailable in few instances. This study was conducted to evaluate the immunogenicity of the RIX4414 vaccine if the vaccine was reconstituted with other agents (e.g. water) instead of CaCO3 buffer. Methods: Healthy infants aged 6–12 weeks, received two oral doses of the RIX4414 vaccine/placebo, reconstituted either with injectable water or CaCO3 buffer according to a 0, 2 month schedule. Seroconversion rates in terms of anti-rotavirus Immunoglobulin A (anti-RV IgA) antibody levels (cut off: ≥ 20U/ml by ELISA) and vaccine take were calculated 2 months post-Dose 2. Solicited and unsolicited symptoms reported during the 15- and 31-day follow-up period after each dose and serious adverse events (SAEs) reported during the entire study period were recorded. Results: There was no statistical difference detected between RIX4414 vaccine reconstituted with buffer or water in vaccine take or in seroconversion rate. The anti-RV IgA seroconversion rate 2 months post-Dose 2 was 84.7% (95% CI: 78.1–90.0) for the group with buffer and 78.6% (95% CI: 71.2–84.8) for the group with water. Solicited and unsolicited symptoms reported were similar across groups. No vaccine related SAEs were reported. Conclusion: Administration of RIX4414 vaccine in the absence of CaCO3 buffer was shown to be well tolerated and immunogenic in Thai infants.

Antibody response to hepatitis B vaccine in infants of HIV-positive mothers.

Hepatitis B remains an important health problem with more than 1500 cases of acute infection occurring each year. HIV-infected adults may be at increased risk of exposure to hepatitis B infection and both diseases can be transferred from mothers to infants. HIV-infected children have inadequate responses to T-cell-dependent vaccines. Suboptimal responses to recombinant DNA hepatitis B virus vaccination were reported in persons with impaired humoral or cellular immunity. We compared hepatitis B vaccine seroresponse rates between HIV-infected and uninfected infants born to HIV positive mothers and further evaluated whether boosters with double dosage could improve immunogenicity in the nonresponders. Full-term infants born to HIV-positive mothers who had no hepatitis B surface antigen (HBsAg) were enrolled. All subjects were born at Phramongkutklao Hospital from January 1996 to March 1998. Written informed consent was obtained and these infants had scheduled clinic visits at 12469 and 12 months of age for routine health care. (excerpt)