The Madin-Darby canine kidney cell culture derived influenza A/H5N1 vaccine: a phase I trial in Taiwan.

BACKGROUND: Avian H5N1 influenza has caused human infections globally and has a high mortality rate. Rapid production of effective vaccines is needed. METHODS: A phase 1, randomized, observer-blinded clinical trial was conducted to examine the safety and immunogenicity of an inactivated whole virion vaccine against the influenza A/H5N1 virus produced from the Madin-Darby canine kidney (MDCK) cell line. Participants were randomized to four groups and administered two intramuscular doses of vaccine containing 3 µg hemagglutinin (HA), 3 µg HA with 300 µg aluminum phosphate (AlPO4), 6 µg HA, and 6 µg HA with 300 µg AlPO4, respectively, at two visits, 21 days apart. Serum hemagglutination inhibition (HAI) and neutralizing antibody levels were determined at baseline and on Days 21 and 42. RESULTS: Sixty healthy individuals were enrolled. The neutralization assay showed a significant immune response in the 6 µg with ALPO4 group on Day 42 compared to pre-vaccination levels (11.32±9.77 vs. 4.00±0, p=0.02). The adjuvant effect in neutralization assay was also significant on Day 42 in the 6 µg group (4.52±1.94 without adjuvant vs. 11.32±9.77 with adjuvant, p=0.02). HAI assay also showed an aluminum adjuvant-induced increasing trend in HAI geometric mean titer on Day 42 in the 3 µg and 6 µg groups (6.02 versus 8.20, p=0.05 and 5.74 versus 8.21, p=0.14). The most frequent adverse event was local pain (20% to 60%). There were no vaccine-related severe adverse effects. CONCLUSION: MDCK cell line-derived H5N1 vaccine was well tolerated. It is necessary to investigate further the immunogenicity of higher antigen doses and the role of aluminum adjuvant in augmenting the effect of the vaccine.

In vitro activity of linezolid, tigecycline, and daptomycin on methicillin-resistant Staphylococcus aureus blood isolates from adult patients, 2006-2008: stratified analysis by vancomycin MIC.

BACKGROUND: The recent molecular epidemiological studies concerning epidemiological studies concerning methicillin-resistant Staphylococcus aureus (MRSA) blood isolates from adult patients and susceptibilities of MRSA isolates with high vancomycin minimum inhibitory concentrations (MICs) (≥2 mg/L) to linezolid, tigecycline, and daptomycin in Taiwan remain limited. The objectives of the study were (1) to better understand the change of molecular epidemiology of MRSA blood isolates and (2) to evaluate the in vitro activity of new anti-Gram-positive agents, including linezolid, tigecycline, and daptomycin. METHODS: A total of 470 nonduplicate MRSA blood isolates from adult patients (older than 18 years) were collected from January 2006 to December 2008. The MICs of these isolates to various antibiotics were determined. Multilocus sequence typing was also performed in all isolates. RESULTS: Three sequence types (STs) constitute most (92.1%) of these 470 MRSA isolates: ST239 (53.2%), ST59 (23.2%), and ST5 (15.7%). Throughout the 3-year study, the ST239 strain remained predominant but with a significant trend of declining annually (p=0.03). In contrast, the proportion of isolates of ST59 increased, although the increment was insignificant (p=0.14). The proportion of MRSA isolates with a vancomycin MIC of 2 mg/L was 17.2%. All of these isolates with a vancomycin MIC of 2 mg/L were susceptible to linezolid and tigecycline, whereas most of them (98.8%) were susceptible to daptomycin. CONCLUSIONS: ST239 remained predominant during the 3-year period but with a significant trend of declining. Moreover, linezolid, tigecycline, and daptomycin remained highly active against MRSA blood isolates, even with a vancomycin MIC of 2 mg/L.

A clinical study to assess the immunogenicity and safety of a monovalent 2009 influenza A (H1N1) vaccine in an area with low-level epidemics of pandemic influenza.

We conducted a multi-center, randomized, laboratory-blinded clinical trial in 185 healthy adults (<60 years) and 107 elders (>60 years) to examine the immunogenicity and safety of different doses of an inactivated, monovalent, non-adjuvanted, split vaccine against the 2009 pandemic influenza A (H1N1) virus. The 186 adults were assigned to three treatment groups, i.e., one 15 µg hemagglutination (HA) antigen dose, two 15 µg or 30 µg HA doses in 3 weeks apart, and the 107 elders were treated with two 15 µg or 30 µg doses in 3 weeks apart. Prior to the vaccination, 4.8% subjects had hemagglutination-inhibition (HAI) antibody titers of 1:40 or more. By day 21 post-vaccination of one dose of 15 µg HA, the seroprotective rate was 95.1% and 75.5% in subjects <60 and >65 years of age, respectively; by day 21 post the second 15 µg HA dose, the seroprotective rates were 93.2% and 73.1%, respectively. The seroprotective rates for recipients of 30 µg HA antigen by day 21 were 95.2% for subjects <60 years and 81.1% for subjects >65 years of age, that was boosted to 98.3% and 80.4%, respectively with a second dose of 30 µg HA antigen. No vaccine-related serious adverse events occurred. The data indicated a single 15 µg HA dose of the vaccine induced a protective immune response in most adults, including the elders >60 years of age, and a booster dose at the third week did not render a higher level of antibody response.

Immune response of single dose vaccination against 2009 pandemic influenza A (H1N1) in the Taiwanese elderly.

We conducted a multi-center, randomized and laboratory-blinded clinical trial with subgroup analyses, involving adults aged greater than 60 years old (range 61-86 years old), to investigate the immunogenicity and the potential factors affecting the immune response of a monovalent, unadjuvanted, inactivated, split-virus vaccine. A total of 107 subjects were randomized to receive 15 and 30 microg of hemagglutinin antigen in a 1:1 ratio. The immunogenicity was detected through hemagglutination inhibition (HAI) test of serum obtained before and 3 weeks after vaccination. By 3 weeks after vaccination, HAI titer >or=1:40 was observed in 75.5% and 81.1% of participants receiving 15 and 30 microg of hemagglutinin antigen, respectively. Positive seroconversion was observed in 71.7% and 81.1% of recipients of the 15 and the 30 microg, respectively. The GMTs increased by a factor of 10.7 and 17.4 in the groups of 15 and 30 microg, respectively. This study indicated that one dose of 15 microg hemagglutinin antigen without adjuvant induced protective immune response in the majority of elderly. Multivariate logistic regression analyses showed that gender, age and diabetes were statistically significant factors affecting the seroprotection rate (p=0.04, 0.01 and 0.01, respectively) and seroconversion rate (p=0.01, 0.01 and 0.01, respectively).

The first case of severe novel H1N1 influenza successfully rescued by extracorporeal membrane oxygenation in Taiwan.

During the novel influenza A (H1N1) pandemic, some patients developed acute respiratory distress syndrome or severe cardiopulmonary failure despite the use of conventional management. Extracorporeal membrane oxygenation (ECMO) support may successfully rescue these severely ill patients. Here, we report the first case of severe novel H1N1 infection with multiorgan failure that was successfully treated with antiviral therapy and ECMO in Taiwan. A 32-year-old man had acute onset of fever, dry cough, rhinorrhea, and sore throat 2 days after returning from Dongguan, China. He attended Hospital A and chest radiography revealed bilateral lung consolidation. Rapid influenza antigen testing was negative. He was intubated 2 days later due to hypoxic respiratory failure and persistent shock refractory to conventional management. Because of compromised cardiopulmonary function, venoarterial ECMO support was started 4 days after the onset of symptoms and he was transferred to Hospital B on July 25, 2009. As history taking found clustering of influenza-like illness, oseltamivir was given immediately under the impression of severe influenza illness. Real-time reverse transcriptase-polymerase chain reaction of respiratory sample for novel H1N1 virus revealed positive results. In addition, blood cultures collected at Hospital A yielded Streptococcus pneumoniae, and beta-hemolytic Streptococcus other than group A, B or D. Hospital course was uneventful and he was discharged 26 days after transfer to Hospital B. This experience showed that ECMO can be life-saving for severe novel H1N1 infection.