冻干水痘减毒活疫苗最小免疫剂量的研究

通过临床研究确定冻干水痘减毒活疫苗的最小免疫剂量 ,为制定规程中的免疫剂量提供科学依据。观察对象接种不同免疫剂量的冻干水痘减毒活疫苗后 ,于接种前和接种后 6周采血 ,采用荧光抗膜抗体 (FAMA)法检测其抗体阳转率和几何平均滴度 (GMT)。接种不同免疫剂量的疫苗 ,抗体阳转率差异无显著的统计学意义。疫苗中抗原含量在 2 5 0 0 0PFU/ml和 2 0 0 0PFU/ml之间 ,GMT差异无显著的统计学意义 ,但 2 5 0 0 0PFU/ml、2 0 0 0PFU/ml与 2 0 0PFU/ml之间抗体GMT的差异有极显著的统计学意义。研究结果表明 ,2 0 0 0PFU/ml为冻干水痘减毒活疫苗的最小免疫剂量。     

乙肝疫苗初免失败婴儿再免疫方法研究

目的探索乙肝疫苗初次全程免疫失败婴儿的再免疫方法.方法对乙肝疫苗全程免疫后乙肝病毒表面抗体(抗-HBs)和乙肝病毒表面抗原(HBsAg)均阴性的144名婴儿,随机分成5组,1组为对照组,其余4组分别采用不同的再免疫方法,观察再免成功率.结果抗-HBs总阳转率为93.79%,抗-HBs几何平均滴度(GMT)为546.97mIU/ml,各组抗-HBs阳转率分别为87.88%、90.91%、100%、96.88%;各组GMT分别为475.34mIU/ml、658.65mIU/ml、625.18mIU/ml、455.90mIU/ml.结论乙肝疫苗初免失败婴儿,再免成功率达93.79%.     

Randomized,double-blind,placebo-controlled,safety and immunogenicity study of 4 formulations of Anthrax Vaccine Adsorbed plus CPG 7909 (AV7909) in healthy adult volunteers

A new anthrax vaccine that could accelerate the immune response and possibly reduce the number of injections needed for protection would be desirable in a post-exposure setting.     

Antibody persistence 5 years after vaccination at 2 to 10 years of age with Quadrivalent MenACWY-CRM conjugate vaccine,and responses to a booster vaccination

BackgroundIn a multi-center extension study, children 2–10 years of age, initially vaccinated with one or two doses (2–5 year-olds) or one dose (6–10 year-olds) of quadrivalent meningococcal CRM₁₉₇-conjugate vaccine (MenACWY-CRM), were assessed five years later for antibody persistence and booster response using serum bactericidal assay with human complement (hSBA).MethodsChildren 7–10 and 11–15 years of age, who received MenACWY-CRM in the original study, and age-matched vaccine-naïve children, were enrolled in this extension study. After an initial blood draw, children received one dose of MenACWY-CRM as booster or primary dose, with a second blood draw 28 days later.ResultshSBA titers decreased five years after primary vaccination, but were higher than in non-vaccinated controls against serogroups C, W and Y, with substantial proportions having titers ≥8: 7–22% for A, 32–57% for C, 74–83% for W, and 48–54% for Y. Previously-vaccinated children demonstrated booster responses to revaccination against all four serogroups. Responses to primary vaccination in vaccine-naïve controls were lower and similar to primary responses observed in the original study. All vaccinations were generally well tolerated, with no safety concern raised.ConclusionsApproximately half the children vaccinated as 2–10 year-olds maintained protective antibodies against serogroups C, W and Y five years later, but fewer did against serogroup A. Declining titers five years after vaccination and robust booster responses suggest that five years may be an appropriate interval to revaccinate children, subject to epidemiology and delivery considerations.     

Immunogenicity and safety of the new intradermal influenza vaccine in adults and elderly: A randomized phase 1/2 clinical trial

BackgroundRecent clinical evidence indicates that an intradermal (ID) delivery of vaccines confers superior immunogenicity as compared to a standard intramusclular or subcutaneous (SC) delivery.MethodsIn this exploratory study, 600 healthy adults were randomized to 6 study groups with subgroups of young adults (20–64 years old) and older adults (65 years and older). The subjects were either injected by a novel ID injection system with a single dose of 6, 9, or 15 μg HA or two doses (21 days apart) of 15 μg HA per strain or injected by an SC injection method with a single or two doses (21 days apart) of 15 μg HA per strain. Immunogenicity was assessed using hemagglutination inhibition (HAI) titer and microneutralization titer on Days 0, 10, 21, and 42. Solicited and unsolicited adverse events were recorded for 7 and 21 days post-vaccination, respectively.ResultsIn both young adults and older adults groups, the geometric titer (GMT) ratios of HAI in the ID 15 μg HA group were higher than those in the SC 15 μg HA group on both Day 10 and Day 21, while those in the ID 6 and ID 9 μg HA groups were comparable with those in the SC 15 μg HA group. The kinetics of GMTs of HAI suggested that the ID vaccine has the potential to induce the prompt immune response, which is rather hampered in older adults as seen in the SC vaccine groups. The injection-site AEs were generally mild and transient, and did not occur in a dose or dosage-dependent manner.ConclusionsThe results of this study clearly suggest that the immunologic profile of the ID vaccine is better than that of the SC vaccine, while the safety profile of the ID vaccine is similar to that of the SC vaccine. In this exploratory study with almost 100 subjects per each group, single or two-dose administration of the ID vaccine containing 15 μg HA was suggested to be an appropriate regimen in order to prevent influenza and to reduce the associated disease burden.Trial registrationJAPIC Clinical Trials Information (JapicCTI-132096).     

A comparative study between outbred and inbred rat strains for the use in in vivo IPV potency testing

In vivo potency testing of inactivated poliovirus vaccines (IPV) is generally performed in rats, although no systematic investigation has identified the most appropriate rat strain for anti-poliovirus antibody quantification. We investigated humoral immune responses to IPV in five different rat strains to identify the most suitable strain. Three outbred (Wistar, Wistar Hannover, Sprague-Dawley) and two inbred rat strains (Fisher 344, Wistar Furth) were immunized intramuscularly with a full or one-fifth human dose of commercial IPV. Anti-poliovirus neutralizing antibody (NA) titers were measured using Salk and Sabin virus neutralizing assays. Post-vaccination responses varied between strains; inbred strains showed greater animal-to-animal variation in NA responses than outbred strains. Virus NA titers persisted for 9 weeks with little reduction in the response. The outbred Wistar rat model was identified as the preferred strain for IPV potency testing based on its capacity to produce high, dose-dependent anti-poliovirus NA responses, with low animal-to-animal variation.     

Safety,tolerability and immunogenicity of intramuscular administration of PRP-CRM197 Hib vaccine to healthy Japanese children: An open-label trial

BackgroundJapan licensed the conjugate Haemophilus influenzae type b vaccine, Vaxem™ Hib, based on clinical studies using subcutaneous injection. The present study was performed to ensure this vaccine is suitable for intramuscular injection in Japanese children.MethodsThirty-one healthy 2–6-month-old infants received three doses of Vaxem™ Hib by intramuscular injection at 4-week intervals and a booster dose 1 year later, concomitant with routine infant (DTaP-IPV and pneumococcal) and toddler (measles–rubella) vaccines. Immunogenicity was assessed before and after the primary series and booster dose by enzyme-linked immunosorbent assay for anti-polyribosyl-ribitol-phosphate (PRP) antibodies. Safety was assessed by medical examination and diary cards completed by the subjects’ parents/legal guardians.ResultsThere were no vaccine-related serious adverse events or withdrawals; all children completed the study. Four weeks after the primary series, the geometric mean anti-PRP titer (GMT) was 19.68 μg/mL, and all children had seroprotective titers (≥0.15 μg/mL) that persisted until the booster dose. Proportions of titers indicative of long-term protection (≥1.0 μg/mL) were 100% after the primary series and 77.4% before the booster. Anamnestic responses to the booster had a GMT of 51.33 μg/mL, and 100% had titers ≥1.0 μg/mL. All but one subject reported injection site reactions as resolved within 3 days of vaccination; systemic reactions due to Hib and routine vaccines were also resolved within this period.ConclusionsVaxem™ Hib was generally well tolerated and immunogenic in Japanese children when administered by intramuscular injection in a three-dose primary series and as a booster with concomitant routine vaccines.Clinical trial registry: Registered on Clinical Trials.gov: NCT02074345.     

Immunogenicity and safety of one or two doses of the quadrivalent meningococcal vaccine MenACWY-TT given alone or with the 13-valent pneumococcal conjugate vaccine in toddlers: A phase III,open-label,randomised study

BackgroundWe evaluated the immunogenicity and safety of 1 and 2 doses of quadrivalent meningococcal serogroup A, C, W and Y tetanus toxoid-conjugate vaccine (MenACWY-TT) given alone or co-administered with 13-valent pneumococcal conjugate vaccine (PCV13) in toddlers.MethodsIn this phase III, open-label, controlled, multicentre study (NCT01939158), healthy toddlers aged 12–14 months were randomised into 4 groups to receive 1 dose of MenACWY-TT at month (M) 0 (ACWY_1), 2 doses of MenACWY-TT at M0 and M2 (ACWY_2), MenACWY-TT and PCV13 at M0 (Co-ad), or PCV13 at M0 and MenACWY-TT at M2 (PCV13/ACWY). Immune responses were assessed 1 month post-each vaccination. Solicited and unsolicited symptoms were recorded for 4 and 31 days post-each vaccination, respectively; serious adverse events (SAEs) and new onset of chronic illnesses (NOCIs) up to M9 from first vaccination.Results802 toddlers were vaccinated. Post-dose 1 of MenACWY-TT, ≥92.8% of toddlers had rSBA titres ≥1:8, and ≥62.5% had hSBA titres ≥1:4 for each meningococcal serogroup. Post-dose 2 of MenACWY-TT, rSBA titres ≥1:8 were observed in ≥98.0% and hSBA titres ≥1:4 in ≥95.3% of toddlers. Percentages of toddlers with hSBA titres ≥1:4 were higher after 2 doses versus 1 dose of MenACWY-TT for MenW (97.1% versus 62.5–68.9%) and MenY (95.3% versus 64.3–67.6%). Non-inferiority of immune responses to co-administered MenACWY-TT and PCV13 over their separate administration was demonstrated. AEs incidence was comparable among groups. SAEs were reported for 4.9%, 5.1%, 5.5% and 7.5%, and NOCIs for 2.0%, 3.0%, 0.5% and 3.5% of toddlers in the ACWY_1, ACWY_2, Co-ad and PCV13/ACWY groups, respectively; 4 SAEs reported in 3 toddlers were vaccine-related. Two fatal vaccine-unrelated SAEs were reported.ConclusionMenACWY-TT was immunogenic when administered as a single dose at 12–14 months of age. A second dose in toddlers increased hSBA responses against MenW and MenY. MenACWY-TT and PCV13 can be co-administered without impairing the immunogenicity or safety profile of either vaccine.     

Immunogenicity and safety of Fluzone intradermal and high-dose influenza vaccines in older adults ≥65 years of age: A randomized,controlled, phase II trial

We conducted a randomized, controlled, multicenter, phase II study to evaluate the immunogenicity and safety of an investigational intradermal (ID) trivalent influenza vaccine (TIV) and a high-dose (HD) intramuscular (IM) TIV in older adults (≥65 years of age). Older adult subjects were immunized with ID vaccine containing either 15 μg hemagglutinin (HA)/strain (n = 636) or 21 μg HA/strain (n = 634), with HD IM vaccine containing 60 μg HA/strain (n = 320), or with standard-dose (SD) IM vaccine (Fluzone^®; 15 μg HA/strain; n = 319). For comparison, younger adults (18–49 years of age) were immunized with SD IM vaccine. In older adults, post-vaccination geometric mean titers induced by the ID vaccines were superior to those induced by the SD IM vaccine for the A/H1N1 and A/H3N2 strains and non-inferior for the B strain. Seroconversion rates induced by the ID vaccines were superior to those induced by the SD IM vaccine in older adults for the A/H1N1 and B strains and non-inferior for the A/H3N2 strain. Results did not differ significantly for the two ID vaccine dosages. Post-vaccination geometric mean titers, seroconversion rates, and most seroprotection rates were significantly higher in HD vaccine recipients than in older adult recipients of the SD IM or ID vaccines and, for most measures, were comparable to those of younger adult SD IM vaccine recipients. Injection-site reactions, but not systemic reactions or unsolicited adverse events, were more common with the ID vaccines than with the IM vaccines. No treatment-related serious adverse events were reported. This study demonstrated that: (1) the ID and HD vaccines were well-tolerated and more immunogenic than the SD IM vaccine in older adults; (2) the HD vaccine was more immunogenic than the ID vaccines in older adults; and (3) the HD vaccine in older adults and the SD IM vaccine in younger adults elicited comparable antibody responses (ClinicalTrials.gov identifier no.: NCT00551031).