Versatility of the adenovirus-vectored foot-and-mouth disease vaccine platform across multiple foot-and-mouth disease virus serotypes and topotypes using a vaccine dose representative of the AdtA24 conditionally licensed vaccine

We investigated the serotype- and topotype versatility of a replication-deficient human adenovirus serotype 5 vectored foot-and-mouth disease (FMD) vaccine platform (AdtFMD). Sixteen AdtFMD recombinant subunit monovalent vaccines targeting twelve distinct FMD virus (FMDV) serotype/topotypes in FMD Regional Pools I-VII were constructed. The AdtA24 serotype conditionally licensed vaccine served as the basis for vaccine design and target dose for cattle clinical trials. Several vaccines contained an additional RGD motif genetic insertion in the adenovector fiber knob, and/or a full-length 2B gene insertion in the FMDV P1 gene cassette. In 13 of the 22 efficacy studies conducted, naïve control and AdtFMD vaccinated cattle were challenged intradermolingually at 2 weeks post-vaccination using a FMDV strain homologous to the AdtFMD vaccine strain. Each of the 16 AdtFMD vaccines were immunogenic based on the presence of homologous neutralizing antibodies in the serum of approximately 90% of total vaccinates (n = 375) on the day of challenge. Importantly, for 75% of vaccines tested, the effective dose that conferred 100% protection against clinical FMD was identical to or in some cases lower than, the minimum protective dose for the conditionally licensed AdtA24 vaccine formulated with ENABL® adjuvant. Results also confirmed the capability of the AdtFMD vaccine platform to differentiate infected from vaccinated animals (DIVA) across the five FMDV serotypes evaluated. Collectively, this comprehensive set of FMD cattle vaccine dose ranging studies highlights the serotype- and topotype versatility of the AdtFMD vaccine platform for further development, licensure, and application in FMD outbreak control and disease eradication efforts.     

A phase II randomized study to determine the safety and immunogenicity of the novel PIKA rabies vaccine containing the PIKA adjuvant using an accelerated regimen

BackgroundHuman Rabies infection continues to be potentially fatal despite the availability of post-exposure prophylaxis with rabies vaccine. The PIKA Rabies vaccine adjuvant is a TLR3 agonist and has been shown to be safe and immunogenic in clinical phase I studies.MethodsWe conducted a phase II, open label, randomized study in healthy adults to assess the safety and immunogenicity of the PIKA rabies vaccine under an accelerated regimen. 126 subjects were randomized into two groups: control vaccine classic regimen (“control-classic”) and PIKA vaccine accelerated regimen (“PIKA-accelerated”). Subjects were followed up for safety and rabies virus neutralizing antibodies (RVNA).ResultsBoth the control and PIKA vaccines were generally well tolerated. 57.6% of subjects in the PIKA vaccine group, compared with 43.8% of subjects in the control-classic group, achieved the target RVNA titer of ≥0.5 IU/mL by Day 7. All subjects achieved the target RVNA titer by Day 14. The RVNA geometric mean titer at Day 7 was 0.60 IU/ml in the PIKA vaccine group and 0.39 IU/ml in the control-classic group. At Day 14, the RVNA geometric mean titer was 18.25 IU/ml in the PIKA-accelerated group and 19.24 IU/ml in the control-classic group. The median time taken to reach the target RVNA titer level of ≥0.5 IU/mL was 7.0 days (95% CI: 7.0–42.0 days) in the PIKA-accelerated group and 14.0 days (95% CI: 7.0–42.0 days) in the control-classic group.ConclusionThe accelerated regimen using the investigational PIKA Rabies vaccine was well-tolerated and demonstrated non-inferior immunogenicity compared to the classic regimen using the commercially available vaccine in healthy adults.Clinical trial registry: The study was registered with clinicaltrials.gov (NCT02956421).     

Influenza vaccination responses: Evaluating impact of repeat vaccination among health care workers

ObjectiveTo compare the antibody response to influenza between health care workers (HCWs) who have received multiple vaccinations (high vaccination group) and those who have received fewer vaccinations (low vaccination group).DesignProspective serosurvey.SettingTertiary referral hospital.ParticipantsHealthcare workers.MethodsHealthcare workers were vaccinated with the 2015 southern hemisphere trivalent influenza vaccine. Influenza antibody titres were measured pre-vaccination, 21–28 days post-vaccination and 6 months post-vaccination. Antibody titres were measured using the haemagglutination inhibition assay. Levels of seropositivity and estimated geometric mean titres were calculated.ResultsOf the 202 HCWs enrolled, 182 completed the study (143 high vaccination and 39 low vaccination). Both vaccination groups demonstrated increases in post-vaccination geometric mean titres, with greater gains in the low vaccination group. Seropositivity remained high in both high and low vaccination groups post-vaccination. The highest fold rise was observed among HCWs in the low vaccination group against the H3N2 component of the vaccine.ConclusionsBoth high and low vaccination groups in our study demonstrated protective antibody titres post-vaccination. The findings from the current study are suggestive of decreased serological response among highly vaccinated HCWs. More studies with larger sample sizes and a greater number of people in the vaccine-naïve and once-vaccinated groups are required to confirm or refute these findings before making any policy changes.     

钩端螺旋体外膜疫苗免疫效果进一步观察

为了对钩端螺旋体(钩体)外膜疫苗的大规模人群使用进行免疫学效果的进一步观察,采集观察对象(6～12岁小学生)免疫前和免疫后1个月、6个月、1年的4份血清,用显微镜凝集试验(MAT)测定抗体.以抗体滴度≥110为阳性判别标准.黄疸出血群的赖型免疫前抗体阴性者和七日热群的七日热型免疫前抗体阴性者接种疫苗后血清抗体阳转率和几何平均滴度(GMT),均在免疫后6个月左右达到高峰,其阳转率分别为96.2%和95.7%,血清抗体GMT分别为187.7和147.48%.免疫后1年的血清抗体阳转率分别为53.9%和29.0%,血清抗体GMT分别为126.43和119.03.钩体外膜疫苗接种1针可至少维持1年,第2年是否加强接种仍需进一步研究.     

丹阳市健康人群麻疹抗体水平分析

目的:了解丹阳市不同人群麻疹抗体水平,为防治工作提供依据。方法:采用ELISA法对抽取的健康人群血清进行麻疹抗体检测,并对结果进行分析。结果:健康人群麻疹IgG抗体阳性率和GMT水平分别为91.68%和1∶730.7,<8月龄儿童的抗体水平最低,抗体阳性率和GMT分别为30.77%和1∶6.42;其次为15岁~组和10岁~组,抗体阳性率和GMT分别为95.73%、1∶634.2和97.69、1∶804.5;男女性别和城乡之间麻疹抗体阳性率无显著性差异。结论:丹阳市人群有较高的麻疹抗体水平,近期不会发生大面积麻疹流行。     

北京市石景山区健康人群甲流抗体水平及疫苗免疫效果

目的了解北京市石景山区健康人群甲型H1N1流感抗体水平及疫苗的免疫效果。方法随机选取10个年龄组共236人作为人群抗体水平监测对象,其中83人作为疫苗免疫效果评估对象,共采集319份静脉血采用血凝抑制试验测定H1抗体。结果健康人群中抗体阳性率为31.36%,几何平均滴度(GMT)为1∶17.22,各年龄组间差异有统计学意义(χ2=57.43,P<0.001;F=9.12,P<0.001),20～59岁组水平最低,职业分布与年龄分布相一致。监测免疫后人群83人,抗体阳性率为95.18%,GMT为1∶184.41,显著高于免疫前水平(χ2=70.58,P<0.001;F=17.59,P<0.001)。结论石景山区人群已具有一定的甲型H1N1流感保护性抗体水平,甲型H1N1流感疫苗具有良好的流行病学保护效果。     

Safety of live attenuated influenza vaccine in mild to moderately immunocompromised children with cancer

Background

The safety of intranasal live-attenuated influenza vaccine (LAIV) in immunocompromised children with cancer is unknown. The objective of this study was to describe the safety and immunogenicity of LAIV in mild to moderately immunocompromised children with cancer.

Methods

We conducted a multicenter, randomized, double-blind study of LAIV versus placebo in children aged 5-17 years with cancer. LAIV (frozen formulation) or allantoic fluid/buffer was administered intranasally. Reactogenicity, adverse events, blood for immune assays, and nasal swabs for viral shedding were obtained during 5 visits over the first 42 days postvaccination; information concerning serious adverse events (SAEs) was collected for 180 days.

Results

20 subjects were enrolled (LAIV, n = 10; placebo, n = 10) with a mean age of 12.2 years. Ten subjects had hematologic malignancy (LAIV, n = 4; placebo, n = 6); 10 subjects had solid tumors (LAIV, n = 6; placebo, n = 4). One subject was excluded from immunogenicity analysis for not receiving a full dose of LAIV. LAIV resulted in an increased incidence of runny nose/nasal congestion occurring in all LAIV recipients; no related SAEs were observed. Four of 10 LAIV recipients shed vaccine virus, with none exceeding 7-10 days duration. LAIV demonstrated modest immunogenicity by hemagglutination inhibition (≥4 fold rise for any strain, 33%) and microneutralization assays (≥4 fold rise for any strain, 44%).

Conclusion

In this small pilot study conducted in mild to moderately immunocompromised children with cancer, runny nose/nasal congestion was increased in LAIV recipients, no related SAEs occurred, and prolonged viral shedding was not detected. Moderate immunogenicity was demonstrated in this small group of individuals. (ClinTrials.gov: NCT00112112).     

Immunogenicity and safety of AS03-adjuvanted H1N1 pandemic vaccines in children and adolescents

Vaccines with acceptable efficacy profile against the H1N1 A/California/7/2009 virus are needed for use in children. The two studies presented here evaluated the immunogenicity and the reactogenicity/safety of A/H1N1/2009 vaccines containing either 3.75 μg haemagglutinin antigen (HA) and AS03_A-adjuvant (3.75 μg HA/AS03_A study) (N = 210 [53, 57 and 100 in the 3-5, 6-9 and 10-17 years age strata, respectively]) or 1.9 μg HA and AS03_B-adjuvant (1.9 μg HA/AS03_B study) (N = 244 [61, 65 and 118 in the 3-5, 6-9 and 10-17 years age strata, respectively]), given as two-dose series. Although the haemagglutination inhibition antibody titres were higher in the 3.75 μg HA/AS03_A study, both vaccine dosages were highly immunogenic and exceeded regulatory acceptance criteria after the first and the second doses. Seroprotection rates reached 100% and seroconversion rates ranged from 98.2% to 99.1% after each dose of both vaccine dosages. Geometric mean titres increased from 456.5 to 1538.5 and from 297.9 to 1106.7 between the first and the second doses in the 3.75 μg HA/AS03_A study and the 1.9 μg HA/AS03_B study, respectively. Despite an observed slight increase of the reactogenicity following the second dose in the 3.75 μg HA/AS03_A study, the vaccines safety profiles were considered clinically acceptable. In conclusion, both dosages of the AS03-adjuvanted A/H1N1/2009 pandemic influenza vaccines were highly immunogenic and well-tolerated in children and adolescents.     

Immunogenicity and safety of a Haemophilus influenzae B (Hib)-hepatitis B vaccine with a modified process hepatitis B component administered with concomitant pneumococcal conjugate vaccine to infants

Background

A hepatitis B vaccine was manufactured with a modified process (mpHBV) that incorporated double the usual amount of phosphate. Following a study in young adults, the mpHBV was evaluated in infants in a combination hepatitis B and Haemophilus influenzae B vaccine (mpHBV-Hib).

Methods

The mpHBV-Hib was compared with the licensed bivalent HBV-Hib vaccine Comvax™ for immunogenicity and safety. Both vaccines contained 5 μg/0.5 mL of hepatitis B surface antigen (HBsAg) and 7.5 μg/0.5 mL of PRP-OMPC (polyribosylribitol phosphate outer membrane protein complex). A total of 543 infants were randomized 1:1 to receive either vaccine at 2, 4 and 12 months of age. A pneumococcal conjugate vaccine (PCV) was given concomitantly. Immunogenicity was assessed at 1-month post-dose 3.

Results

Seroprotection rates [% subjects with anti-hepatitis B surface antigen antibody titers (anti-HBs) ≥10 mIU/mL)] were 100% and 99% for mpHBV-Hib and the licensed control (Comvax™), respectively. Anti-HBs geometric mean titers (GMTs) were 4204 (95% CI, 3411-5182) and 1683 (95% CI, 1350-2099) mIU/mL, respectively. Anti-PRP seroprotection rates (SPR) at ≥0.15 μg/mL and at ≥1.0 μg/mL were 97% and 94%, respectively, for mpHBV-Hib and 96% and 92%, respectively, for the control. Anti-PRP GMTs were 7.1 μg/mL for mpHBV-Hib and 8.0 μg/mL for the control. Reactogenicity of the two vaccines was similar.

Conclusions

The mpHBV in combination with Hib and with co-administered PCV was highly immunogenic. The safety profile of mpHBV-Hib was comparable to the licensed control. Both the control and mpHBV-Hib met acceptability criteria for seroprotection rates to hepatitis B, with higher anti-HBs GMTs noted for mpHBV-Hib.     

Immunological priming induced by a two-dose series of H5N1 influenza antigen, administered alone or in combination with two different formulations of AS03 adjuvant in adults: results of a randomised single heterologous booster dose study at 15 months

One influenza pandemic preparedness strategy involves priming a population with a pre-pandemic subtype-specific vaccine and boosting the immunological response at the time of the pandemic with a strain-matched vaccine. In the current study, adults (n = 469) randomised 15 months previously to receive an A/Indonesia/5/2005 (H5N1) influenza vaccine (3.75 μg haemagglutinin antigen [HA]) administered alone or in combination with an oil-in-water emulsion based Adjuvant System containing 11.86 mg (AS03_A) or 5.93 mg (AS03_B) tocopherol per dose, received one booster dose of A/turkey/Turkey/1/2005 (H5N1) vaccine (3.75 μg HA) with or without AS03_A. An anamnestic antibody response that met US regulatory acceptance criteria was observed 15 months after priming. Although superior immunogenicity of AS03-adjuvanted compared to unadjuvanted priming was not demonstrated, higher antibody titres which persisted longer were seen when both priming and boosting regimens were adjuvanted. This may affect duration of response or heterologous immunity. The booster vaccines had a clinically acceptable safety/reactogenicity profile after adjuvanted or unadjuvanted priming. This study has been registered at www.clinicaltrials.govNCT00771615.