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Immunogenicity and safety of a quadrivalent plant-derived virus like particle influenza vaccine candidate-Two randomized Phase II clinical trials in 18 to 49 and ?50 years old adults.

ABSTRACT: BACKGROUND:New influenza vaccines eliciting more effective protection are needed, particularly for the elderly who paid a large and disproportional toll of hospitalization and dead during seasonal influenza epidemics. Low (?15 ?g/strain) doses of a new plant-derived virus-like-particle (VLP) vaccine candidate have been shown to induce humoral and cellular responses against both homologous and heterologous strains in healthy adults 18-64 years of age. The two clinical trials reported here addressed the safety and immunogenicity of higher doses (?15 ?g/strain) of quadrivalent VLP candidate vaccine on 18-49 years old and ?50 years old subjects. We also investigated the impact of alum on the immunogenicity induced by lower doses of the vaccine candidate. METHOD:In the first Phase II trial reported here (NCT02233816), 18-49 year old subjects received 15, 30 or 60 ?g/strain of a hemagglutinin-bearing quadrivalent virus-like particle (QVLP) vaccine or placebo. In the second trial (NCT02236052), ?50 years old subjects received QVLP as above or placebo with additional groups receiving 7.5 or 15 ?g/strain with alum. Along with safety recording, the humoral and cell-mediated immune responses were analyzed. RESULTS:Local and systemic side-effects were similar to those reported previously. The QVLP vaccine induced significant homologous and heterologous antibody responses at the two higher doses, the addition of alum having little-to-no effect. Serologic outcomes tended to be lower in ?50 years old subjects previously vaccinated. The candidate vaccine also consistently elicited both homologous and heterologous antigen-specific CD4+ T cells characterized by their production of interferon-gamma (IFN-?), interleukine-2 (IL-2) and/or tumor-necrosis factor alpha (TNF-?) upon ex vivo antigenic restimulation. CONCLUSION:Overall, the 30 ?g dose produced the most consistent humoral and cellular responses in both 18-49 and ?50 years old subjects, strongly supporting the clinical development of this candidate vaccine. That particular dose was chosen to test in the ongoing Phase III clinical trial.

SUBMITTER: Pillet S

PROVIDER: S-EPMC6550445 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Immunogenicity and safety of a quadrivalent plant-derived virus like particle influenza vaccine candidate-Two randomized Phase II clinical trials in 18 to 49 and ≥50 years old adults.

Pillet Stéphane S Couillard Julie J Trépanier Sonia S Poulin Jean-François JF Yassine-Diab Bader B Guy Bruno B Ward Brian J BJ Landry Nathalie N

PloS one 20190605 6

<h4>Background</h4>New influenza vaccines eliciting more effective protection are needed, particularly for the elderly who paid a large and disproportional toll of hospitalization and dead during seasonal influenza epidemics. Low (≤15 μg/strain) doses of a new plant-derived virus-like-particle (VLP) vaccine candidate have been shown to induce humoral and cellular responses against both homologous and heterologous strains in healthy adults 18-64 years of age. The two clinical trials reported here ...[more]

PMID: 31166987

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Project description:BackgroundTwo antigenically distinct influenza B lineages have co-circulated since the 1980s, yet inactivated trivalent influenza vaccines (TIVs) include strains of influenza A/H1N1, A/H3N2, and only one influenza B from either the Victoria or Yamagata lineage. This means that exposure to B-lineage viruses mismatched to the TIV is frequent, reducing vaccine protection. Formulations including both influenza B lineages could improve protection against circulating influenza B viruses. We assessed a candidate inactivated quadrivalent influenza vaccine (QIV) containing both B lineages versus TIV in adults in stable health.MethodsA total of 4659 adults were randomized 5:5:5:5:3 to receive one dose of QIV (one of three lots) or a TIV containing either a B/Victoria or B/Yamagata strain. Hemagglutination-inhibition assays were performed pre-vaccination and 21-days after vaccination. Lot-to-lot consistency of QIV was assessed based on geometric mean titers (GMT). For QIV versus TIV, non-inferiority against the three shared strains was demonstrated if the 95% confidence interval (CI) upper limit for the GMT ratio was ≤1.5 and for the seroconversion difference was ≤10.0%; superiority of QIV versus TIV for the alternate B lineage was demonstrated if the 95% CI lower limit for the GMT ratio was > 1.0 and for the seroconversion difference was > 0%. Reactogenicity and safety profile of each vaccine were assessed. Clinicaltrials.gov: NCT01204671.ResultsConsistent immunogenicity was demonstrated for the three QIV lots. QIV was non-inferior to TIV for the shared vaccine strains, and was superior for the added alternate-lineage B strains. QIV elicited robust immune responses against all four vaccine strains; the seroconversion rates were 77.5% (A/H1N1), 71.5% (A/H3N2), 58.1% (B/Victoria), and 61.7% (B/Yamagata). The reactogenicity and safety profile of QIV was consistent with TIV.ConclusionsQIV provided superior immunogenicity for the additional B strain compared with TIV, without interfering with antibody responses to the three shared antigens. The additional antigen did not appear to alter the safety profile of QIV compared with TIV. This suggests that the candidate QIV is a viable alternative to TIV for use in adults, and could potentially improve protection against influenza B.Trial registrationClinical Trials.gov: NCT01204671/114269.

Project description:Objective: Chronic Subdural Hematoma (cSDH) is primarily a disease of elderly, and is rare in patients <50 years, and this may in part be related to the increased brain atrophy from 50 years of age. This fact may also influence clinical presentation and outcome. The aim of this study was to study the clinical course with emphasis on clinical presentation of cSDH patients in the young (<50 years). Methods: A retrospective review of a population-based cohort of 1,252 patients operated for cSDH from three Scandinavian neurosurgical centers was conducted. The primary end-point was difference in clinical presentation between the patients <50 y/o and the remaining patients (≥50 y/o group). The secondary end-points were differences in perioperative morbidity, recurrence and mortality between the two groups. In addition, a meta-analysis was performed comparing clinical patterns of cSDH in the two age groups. Results: Fifty-two patients (4.2%) were younger than 50 years. Younger patients were more likely to present with headache (86.5% vs. 37.9%, p < 0.001) and vomiting (25% vs. 5.2%, p < 0.001) than the patients ≥50 y/o, while the ≥50 y/o group more often presented with limb weakness (17.3% vs. 44.8%, p < 0.001), speech impairment (5.8% vs. 26.2%, p = 0.001) and gait disturbance or falls (23.1% vs. 50.7%, p < 0.001). There was no difference between the two groups in recurrence, overall complication rate and mortality within 90 days. Our meta-analysis confirmed that younger patients are more likely to present with headache (p = 0.015) while the hemispheric symptoms are more likely in patients ≥50 y/o (p < 0.001). Conclusion: Younger patients with cSDH present more often with signs of increased intracranial pressure, while those ≥50 y/o more often present with hemispheric symptoms. No difference exists between the two groups in terms of recurrence, morbidity, and short-term mortality. Knowledge of variations in clinical presentation is important for correct and timely diagnosis in younger cSDH patients.

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Project description:Colorectal cancer (CRC) is the third most diagnosed cancer worldwide and second leading cause of cancer death. Most CRCs arise from a polyp, developing through two major precursor lesion pathways: the traditional adenoma-carcinoma pathway, and the serrated neoplasia pathway. This provides opportunities to prevent cancer by removing its precursor lesions. CRC screening efforts are directed toward removal of precancerous polyps with colonoscopy and detection of early-stage CRC, which has been demonstrated to reduce CRC incidence and mortality effectively, making CRC one of the most preventable and treatable forms of cancer. Current guidelines in China recommend starting CRC screening uniformly at age 50 in average-risk individuals. However, a one-fits-all approach to determining CRC screening starting age may be not conducive to personalized screening, especially in the developing countries with scarce health resources. The incidence of early-onset CRC (CRC diagnosed before the age of 50) has shown a continuous increasing trend worldwide, spurring the US Preventive Services Task Force to recommend initiating average-risk CRC screening at age 45 instead of 50. Furthermore, different populations may benefit from even earlier screening, and CRC incidence may differ on the basis of population characteristics and CRC risk factors. For individuals younger than 50 years old, earlier screening based on risk factors may address this concern. Previous studies have recommended earlier starting age of CRC screening combined with risk factors such as but not limited to sex, age, family history, lifestyle and comorbidity. Some upper gastrointestinal diseases have also been reported to be associated with an increased risk of colorectal neoplasms, which may be related to the destruction of gastric acid barrier function and long-term use of pump proton inhibitors. Compared with colonoscopy examination, individuals were more willing to undergo esophagogastroduodenoscopy (EGD) examination for gastric cancer screening, especially among the younger, potentially utilizing the EGD to guide earlier colonoscopies for patients at increased risk. Therefore, this study was aimed to investigate the association between esophagogastric histopathology and colorectal neoplasms in patients under the age of 50 and whether these risks factor could be combined with to guide earlier CRC screening.

Dataset Information

Immunogenicity and safety of a quadrivalent plant-derived virus like particle influenza vaccine candidate-Two randomized Phase II clinical trials in 18 to 49 and ?50 years old adults.

Publications

Immunogenicity and safety of a quadrivalent plant-derived virus like particle influenza vaccine candidate-Two randomized Phase II clinical trials in 18 to 49 and ≥50 years old adults.

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