One year immunogenicity and safety of subunit plague vaccine in Chinese healthy adults: An extended open-label study.
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ABSTRACT:
SUBMITTER: Hu J
PROVIDER: S-EPMC6351024 | biostudies-literature | 2018
REPOSITORIES: biostudies-literature
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One year immunogenicity and safety of subunit plague vaccine in Chinese healthy adults: An extended open-label study.
Hu Jialei J Jiao Lei L Hu Yuemei Y Chu Kai K Li Jingxin J Zhu Fengcai F Li Taishun T Wu Zhiyuan Z Wei Dong D Meng Fanyue F Wang Bingxiang B
Human vaccines & immunotherapeutics 20180711 11
<h4>Background</h4>To evaluate the one-year immunogenicity and safety of a subunit plague vaccine.<h4>Methods</h4>In the initial study, 240 healthy adults aged 18-55 years were administrated with 2 doses of 15 or 30 µg plague vaccines at day 0 and 28, respectively. In this extended follow-up study, we evaluated the immunogenicity and safety of the plague vaccine up to one year.<h4>Results</h4>For antibody to envelope antigen faction 1 (F1) antigen, titers were up to new peaks at month 6, then de ...[more]
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Project description:BackgroundAlthough the killed whole-cell and live attenuated plague vaccine have been licensed, they are rarely used today because of toxicities, limited evidence of efficacy against plague, poor immune persistence required booster immunization every year, and limited commercial availability. This study was a randomized phase 2a clinical trial aimed to evaluating the immunogenicity and safety of a novel subunit plague vaccine.Methods240 healthy adults aged 18-55 y were enrolled and randomly assigned at a ratio of 1:1 to receive 2 doses of 15 or 30 mcg vaccine at a 28-day interval between doses. Blood samples were collected at day 0, 28 and 56. Adverse events were collected during the first 28 d after each vaccination. Serious Adverse Event was observed throughout the study period.Results239 participants received the first dose at day 0 and 238 received the second dose at day 28. Antibodies to envelope antigen faction 1 (F1) and recombinant virulence antigen (rV) were increased at day 28, and boosted significantly at day 56. For anti-F1 antibodies, geometric mean titer (GMT) and geometric mean fold increase (GMFI) were significantly higher in 30 mcg group than in the 15 mcg group(each P1< 0.05 at day 28 and each P1< 0.001 at day 56), with similar seroconversion rate of antibodies between 15 and 30 mcg group at both of the 2 time points. For anti-rV antibodies, seroconversion rate at day 28 in 30 mcg group was higher than that in 15 mcg group. However, GMT and GMFI of anti-rV antibodies were increased to approximately the same levels in the 2 groups. Similar booster immune response was also noticed in both groups at day 56. The injections were well tolerated, with mainly mild or moderate local and systemic adverse reactions (lower than grad 3). The proportion of pain at injection site was higher in 30 mcg group. None of SAEs were reported during 56 d.ConclusionThe plague vaccine comprised of F1 and rV antigens showed good safety and immunogenicity in adults aged 18-55 y old. The data show that the 30 mcg formulation is generally more immunogenic than the 15 mcg formulation, and represents the preferred formulation for further clinical development. It will be important to evaluate the long-term efficacy for appropriate formulations of the plague subunit vaccine.
| S-EPMC5027722 | biostudies-literature
Project description:Varicella (chickenpox) is a common, highly contagious disease caused by primary infection with varicella zoster virus (VZV). Adults typically experience more severe symptoms than children and have a higher risk of developing complications. Stage 1 of this Phase 3 open-label study enrolled healthy adults in Russia aged 18-75 years without a clinical history of varicella infection. Eligible participants (n = 50) were administered 2 doses of VARIVAX™ (Varicella Virus Vaccine Live [Oka/Merck]) 0.5 mL 6 weeks apart. For participants seronegative at baseline (VZV antibody titer <1.25 glycoprotein enzyme-linked immuno-sorbent assay [gpELISA] units/mL), immunogenicity was assessed by seroconversion (VZV antibody titer ≥5 gpELISA units/mL) and assessment of geometric mean titers of VZV antibody as measured by gpELISA 6 weeks after Dose 2. For VZV seropositive participants at baseline (VZV antibody titer ≥1.25 gpELISA units/mL), immunogenicity was assessed by geometric mean fold rise in antibody titer and percentage of participants with a ≥ 4-fold rise in antibody titer 6 weeks after Dose 2. A Vaccine Report Card was used to record solicited and unsolicited adverse events through 42 days post-vaccination. All participants who were seronegative (n = 26) at baseline demonstrated seroconversion 6 weeks after Dose 2. Among participants who were seropositive at baseline (n = 23), 60.9% had a ≥4-fold rise in antibody titer 6 weeks after Dose 2. Vaccination was generally well tolerated, with no new safety signals identified. Administration of 2 doses of VARIVAX in adults in Russia results in acceptable immune responses with safety data consistent with the licensed product (Clinicaltrials.gov identifier: NCT03843632).
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Project description:BackgroundThe Zika virus epidemic and associated congenital infections have prompted rapid vaccine development. We assessed two new DNA vaccines expressing premembrane and envelope Zika virus structural proteins.MethodsWe did two phase 1, randomised, open-label trials involving healthy adult volunteers. The VRC 319 trial, done in three centres, assessed plasmid VRC5288 (Zika virus and Japanese encephalitis virus chimera), and the VRC 320, done in one centre, assessed plasmid VRC5283 (wild-type Zika virus). Eligible participants were aged 18-35 years in VRC19 and 18-50 years in VRC 320. Participants were randomly assigned 1:1 by a computer-generated randomisation schedule prepared by the study statistician. All participants received intramuscular injection of 4 mg vaccine. In VRC 319 participants were assigned to receive vaccinations via needle and syringe at 0 and 8 weeks, 0 and 12 weeks, 0, 4, and 8 weeks, or 0, 4, and 20 weeks. In VRC 320 participants were assigned to receive vaccinations at 0, 4, and 8 weeks via single-dose needle and syringe injection in one deltoid or split-dose needle and syringe or needle-free injection with the Stratis device (Pharmajet, Golden, CO, USA) in each deltoid. Both trials followed up volunteers for 24 months for the primary endpoint of safety, assessed as local and systemic reactogenicity in the 7 days after each vaccination and all adverse events in the 28 days after each vaccination. The secondary endpoint in both trials was immunogenicity 4 weeks after last vaccination. These trials are registered with ClinicalTrials.gov, numbers NCT02840487 and NCT02996461.FindingsVRC 319 enrolled 80 participants (20 in each group), and VRC 320 enrolled 45 participants (15 in each group). One participant in VRC 319 and two in VRC 320 withdrew after one dose of vaccine, but were included in the safety analyses. Both vaccines were safe and well tolerated. All local and systemic symptoms were mild to moderate. In both studies, pain and tenderness at the injection site was the most frequent local symptoms (37 [46%] of 80 participants in VRC 319 and 36 [80%] of 45 in VRC 320) and malaise and headache were the most frequent systemic symptoms (22 [27%] and 18 [22%], respectively, in VRC 319 and 17 [38%] and 15 [33%], respectively, in VRC 320). For VRC5283, 14 of 14 (100%) participants who received split-dose vaccinations by needle-free injection had detectable positive antibody responses, and the geometric mean titre of 304 was the highest across all groups in both trials.InterpretationVRC5283 was well tolerated and has advanced to phase 2 efficacy testing.FundingIntramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health.
| S-EPMC6379903 | biostudies-literature
Project description:This open-label study was designed to assess immunogenicity and safety of 13-valent pneumococcal conjugate vaccine (PCV13) when administered to Japanese adults aged ≥50 years not previously vaccinated with 23-valent pneumococcal polysaccharide vaccine and to compare this Japanese study population with similar study populations in the United States (US; 50-64 years age group) and European Union (EU; ≥65 years age group). Functional antibody immune responses were measured by opsonophagocytic activity assays. Immune responses in both Japanese age groups showed significant pre/postvaccination fold rises for each serotype. In the Japanese 50-64 years age group, immune responses for the majority of serotypes were significantly lower than in the ≥65 years Japanese age group and generally lower than in the 50-64 years age group in the US study. Immune responses in the Japanese ≥65 years age group were significantly higher for the majority of serotypes compared with the ≥65 years age group in the EU study. The safety profiles across age groups and studies were generally similar. In conclusion, PCV13 elicited robust immune responses in the Japanese study population. The unanticipated higher immune responses observed in the older age group in the Japanese study are of interest and of potential benefit given the higher incidence of pneumococcal disease in older adults. PCV13 was well tolerated and safe.
| S-EPMC4186023 | biostudies-literature
Project description:BackgroundBecause the general population is largely naive to H5N1 influenza, antibodies generated to H5 allow analysis of novel influenza vaccines independent of background immunity from previous infection. We assessed the safety and immunogenicity of DNA encoding H5 as a priming vaccine to improve antibody responses to inactivated influenza vaccination.MethodsIn VRC 306 and VRC 310, two sequentially enrolled phase 1, open-label, randomised clinical trials, healthy adults (age 18-60 years) were randomly assigned to receive intramuscular H5 DNA (4 mg) at day 0 or twice, at day 0 and week 4, followed by H5N1 monovalent inactivated vaccine (MIV; 90 μg) at 4 or 24 weeks, and compared with a two-dose regimen of H5N1 MIV with either a 4 or 24 week interval. Antibody responses were assessed by haemagglutination inhibition (HAI), ELISA, neutralisation (ID(80)), and immunoassays for stem-directed antibodies. T cell responses were assessed by intracellular cytokine staining. After enrolment, investigators and individuals were not masked to group assignment. VRC 306 and VRC 310 are registered with ClinicalTrials.gov, numbers NCT00776711 and NCT01086657, respectively.FindingsIn VRC 306, 60 individuals were randomly assigned to the four groups (15 in each) and 59 received the vaccinations. In VRC 310, of the 21 individuals enrolled, 20 received the vaccinations (nine received a two-dose regimen of H5N1 MIV and 11 received H5 DNA at day 0 followed by H5N1 MIV at week 24). H5 DNA priming was safe and enhanced H5-specific antibody titres following an H5N1 MIV boost, especially when the interval between DNA prime and MIV boost was extended to 24 weeks. In the two studies, DNA priming with a 24-week MIV boost interval induced protective HAI titres in 21 (81%) of 26 of individuals, with an increase in geometric mean titre (GMT) of more than four times that of individuals given the MIV-MIV regimen at 4 or 24 weeks (GMT 103-206 vs GMT 27-33). Additionally, neutralising antibodies directed to the conserved stem region of H5 were induced by this prime-boost regimen in several individuals. No vaccine-related serious adverse events were recorded.InterpretationDNA priming 24 weeks in advance of influenza vaccine boosting increased the magnitude of protective antibody responses (HAI) and in some cases induced haemagglutinin-stem-specific neutralising antibodies. A DNA-MIV vaccine regimen could enhance the efficacy of H5 or other influenza vaccines and shows that anti-stem antibodies can be elicited by vaccination in man.FundingNational Institutes of Health.
| S-EPMC7185472 | biostudies-literature
Project description:An adjuvanted recombinant subunit candidate vaccine (HZ/su) containing varicella zoster virus envelope glycoprotein E was developed for the prevention of herpes zoster and its complications. This study evaluated safety and reactogenicity of HZ/su in an ethnic Japanese population. This was a phase I, open-label and single-center study conducted between March and November of 2010 in Australia. Twenty healthy ethnic Japanese subjects, aged 18-30 y and 50-69 y (1:1) were enrolled. Subjects were administered two doses of HZ/su vaccine according to a 0, 2-mo schedule. Local and general solicited symptoms were recorded for 7 d post-vaccination. Unsolicited symptoms were recorded for 30 d post-vaccination. Serious adverse events (SAEs), new onset of autoimmune disease (NOAD), other potential immune mediated disorders and HZ cases were recorded throughout the study period. All 20 subjects were included in the according-to-protocol cohort for safety. A total of 18 subjects were included in the according-to-protocol cohort for immunogenicity: 10 in the 18-30 y age group and 8 in the 50-69 y age group. The most commonly reported local and general solicited symptoms were pain and fatigue in both groups. Back pain (in the 18-30 y age group) and chills (in the 50-69 y age group) were the most frequently reported unsolicited symptoms. There were no reports of death, SAEs, NOADs, other autoimmune mediated inflammatory disorder or suspected HZ cases. This study indicated that the two-dose regimen of HZ/su exhibited a clinically acceptable safety profile in healthy young and older ethnic Japanese adults.
| S-EPMC3890214 | biostudies-literature
Project description:Abstract Background Herpes zoster vaccination is recommended to patients with a prior history of herpes zoster to prevent reactivation. However, the appropriate timing of vaccination is controversial. We compared immunogenicity of vaccine according to timing of vaccination after zoster illness. Methods In this prospective observational study, subjects were stratified into two groups by the vaccination timing since their zoster illness: 6–12 months (within-1 year group) vs. 1–5 years (after-1 year group). Blood samples were collected before and 6 weeks after vaccination of zoster vaccine live. Varicella-zoster virus (VZV)-specific IgG concentrations were measured by enzyme-linked immunosorbent assay. Interferon-gamma enzyme-linked immunosorbent spot (ELISPOT) assays were performed to assess VZV specific T-cell responses. Results A total of 59 patients (18 in the within-1 year group and 41 in the after-1 year group) were enrolled. Ages were not significantly different between groups. The baseline geometric mean titer (GMT) of VZV IgG was higher in the within-1 year group than in the after-1 year group (245.8 IU/mL vs. 124.9 IU/mL; P = 0.040). The geometric mean fold-rise (GMFR) of VZV IgG was lower in the within-1 year group than in the after-1 year group (1.42 vs. 2.46; P = 0.002). The GMT of spot forming cell (SFC) counts by ELISPOT at baseline and 6 weeks after vaccination were not significantly different between groups. The GMFRs of SFCs were also comparable. Conclusion Zoster vaccination within 1 year after zoster illness may have disadvantage in the aspect of humoral immune response (ClinicalTrials.gov number, NCT02704572). Disclosures All authors: No reported disclosures.
| S-EPMC5630997 | biostudies-literature
Project description:BackgroundChAdOx1-vectored vaccine candidates against several pathogens have been developed and tested in clinical trials and ChAdOx1 nCoV-19 has now been licensed for emergency use for COVID-19. We assessed the safety and immunogenicity of the ChAdOx1 MERS vaccine in a phase 1b trial in healthy Middle Eastern adults.MethodMERS002 is an open-label, non-randomised, dose-escalation, phase 1b trial. Healthy Middle Eastern adults aged 18-50 years were included in the study. ChAdOx1 MERS was administered as a single intramuscular injection into the deltoid muscle of the non-dominant arm at three different dose groups: 5·0 × 109 viral particles in a low-dose group, 2·5 × 1010 viral particles in an intermediate-dose group, and 5·0 × 1010 viral particles in a high-dose group. The primary objective was to assess the safety and tolerability of ChAdOx1 MERS, measured by the occurrence of solicited and unsolicited adverse events after vaccination for up to 28 days and occurrence of serious adverse events up to 6 months. The study is registered with ClinicalTrials.gov, NCT04170829.FindingsBetween Dec 17, 2019, and June 1, 2020, 24 participants were enrolled (six to the low-dose, nine to the intermediate-dose, and nine to the high-dose group) and received a dose; 23 were available for follow-up at 6 months. The one dose of ChAdOx1 MERS vaccine was well tolerated with no serious adverse event reported during the 6 months of follow-up. Most adverse events were mild (67, 74%) and moderate (17, 19%). Six (7%) severe adverse events were reported by two participants in the intermediate-dose group (two feverish, two headache, one joint pain, and one muscle pain). Pain at the injection site was the most common local and overall adverse event, reported by 15 (63%) of the 24 participants. The most common systemic adverse event was headache, reported by 14 (58%), followed by muscle pain reported by 13 (54%). The vaccine induced both antibody and T cell immune responses in all volunteers; antibodies peaked at day 28 and T cell responses peaked at day 14; and continued until the end of follow-up at 6 months.InterpretationThe acceptable safety and immunogenicity data from this phase 1b trial of ChAdOx1 MERS vaccine candidate in Healthy Middle Eastern adults, combined with previous safety and immunogenicity data from a trial in the UK, support selecting the ChAdOx1 MERS vaccine for advancement into phase 2 clinical evaluation.FundingUK Department of Health and Social Care, using UK Aid funding, managed by the UK National Institute for Health Research; and King Abdullah International Medical Research Center.
| S-EPMC8565931 | biostudies-literature
Project description:Varicella (chickenpox) is a common, highly contagious disease caused by primary infection with varicella zoster virus (VZV), which can result in bacterial superinfection, central nervous system complications, and hospitalization. Stage 2 of this Phase 3 open-label study (ClinicalTrials.gov identifier: NCT03843632) enrolled 100 healthy infants, children, and adolescents (12 months-6 years, n = 37; 7-12 years, n = 33; 13-17 years, n = 30) without a clinical history of varicella. Participants aged 12 months-12 years were administered 1 dose of VARIVAX™ 0.5 mL (Varicella Virus Vaccine Live [Oka/Merck]) and adolescents aged 13-17 years were administered 2 doses 6 weeks apart. For participants seronegative at baseline (VZV antibody titer <1.25 glycoprotein enzyme-linked immunosorbent assay [gpELISA] units/mL), immunogenicity was assessed by seroconversion (VZV antibody titer ≥5 gpELISA units/mL) and VZV antibody geometric mean titers 6 weeks after the final dose. For participants who were VZV seropositive at baseline (VZV antibody titer ≥1.25 gpELISA units/mL), immunogenicity was assessed by antibody titer geometric mean fold rise and percentage of participants with ≥4-fold rise in antibody titer 6 weeks after the final dose. A Vaccine Report Card was used to report solicited and unsolicited adverse events through 42 days post-vaccination. After series completion among seronegative participants across age groups (n = 74), 98.6% demonstrated seroconversion 6 weeks post-vaccination; among seropositive participants (n = 26), 65.4% had ≥4-fold rise in antibody titer 6 weeks post-vaccination. No new safety signals were observed. Administering VARIVAX to infants, children, and adolescents resulted in an acceptable immune response with a safety profile consistent with the licensed product.
| S-EPMC8828090 | biostudies-literature
Project description:BackgroundPromising clinical data and significant antigen-sparing have been demonstrated for a pandemic H5N1 influenza split-virion vaccine adjuvanted with AS03A, an α-tocopherol-containing oil-in-water emulsion-based Adjuvant System. Although studies using this formulation have been reported, there have been no data for Japanese populations. This study therefore aimed to assess the immunogenicity and tolerability of a prepandemic (H5N1) influenza vaccine adjuvanted with AS03A in Japanese adults.MethodsThis open-label, single-group study was conducted at two centres in Japan in healthy Japanese males and females aged 20-64 years (n = 100). Subjects received two doses of vaccine, containing 3.75 μg haemagglutinin of the A/Indonesia/5/2005-like IBCDC-RG2 Clade 2.1 (H5N1) strain adjuvanted with AS03A, 21 days apart. The primary endpoint evaluated the humoral immune response in terms of H5N1 haemagglutination inhibition (HI) antibody titres against the vaccine strain (Clade 2.1) 21 days after the second dose. Ninety five percent confidence intervals for geometric mean titres, seroprotection, seroconversion and seropositivity rates were calculated. Secondary and exploratory endpoints included the assessment of the humoral response in terms of neutralising antibody titres, the response against additional H5N1 strains (Clade 1 and Clade 2.2), as well as the evaluation of safety and reactogenicity.ResultsRobust immune responses were elicited after two doses of the prepandemic influenza vaccine adjuvanted with AS03A. Overall, vaccine HI seroconversion rates and seroprotection rates were 91% 21 days after the second vaccination. This fulfilled all regulatory acceptance criteria for the vaccine-homologous HI antibody level. A substantial cross-reactive humoral immune response was also observed against the virus strains A/turkey/Turkey/1/2005 (Clade 2.2) and A/Vietnam/1194/2004 (Clade 1) after the second vaccine administration. A marked post-vaccination response in terms of neutralising antibody titres was demonstrated and persistence of the immune response was observed 6 months after the first dose. The vaccine was generally well tolerated and there were no serious adverse events reported.ConclusionsThe H5N1 candidate vaccine adjuvanted with AS03A elicited a strong and persistent immune response against the vaccine strain A/Indonesia/5/2005 in Japanese adults. Vaccination with this formulation demonstrated a clinically acceptable reactogenicity profile and did not raise any safety concerns in this population.Trial registrationClinicaltrials.gov NCT00742885.
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