scholarly journals ChAdOx1 nCoV-19 (AZD1222) vaccine candidate significantly reduces SARS-CoV-2 shedding in ferrets

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Glenn A. Marsh ◽  
Alexander J. McAuley ◽  
Gough G. Au ◽  
Sarah Riddell ◽  
Daniel Layton ◽  
...  
Keyword(s):  
Intranasal Administration ◽  
Vaccine Candidate ◽  
Phase Iii ◽  
Intranasal Route ◽  
Nasal Wash ◽  
Oral Swab ◽  
Viral Loads ◽  
Safe Vaccine ◽  
Preclinical Trials ◽  
Vectored Vaccine

AbstractVaccines against SARS-CoV-2 are likely to be critical in the management of the ongoing pandemic. A number of candidates are in Phase III human clinical trials, including ChAdOx1 nCoV-19 (AZD1222), a replication-deficient chimpanzee adenovirus-vectored vaccine candidate. In preclinical trials, the efficacy of ChAdOx1 nCoV-19 against SARS-CoV-2 challenge was evaluated in a ferret model of infection. Groups of ferrets received either prime-only or prime-boost administration of ChAdOx1 nCoV-19 via the intramuscular or intranasal route. All ChAdOx1 nCoV-19 administration combinations resulted in significant reductions in viral loads in nasal-wash and oral swab samples. No vaccine-associated adverse events were observed associated with the ChAdOx1 nCoV-19 candidate, with the data from this study suggesting it could be an effective and safe vaccine against COVID-19. Our study also indicates the potential for intranasal administration as a way to further improve the efficacy of this leading vaccine candidate.

scholarly journals Immunogenicity and Protective Efficacy of an Intranasal Live-attenuated Vaccine Against SARS-CoV-2 in Preclinical Animal Models

2021 ◽  
Author(s):  
Jun-Guy Park ◽  
Fatai S. Oladunni ◽  
Mohammed A. Rohaim ◽  
Jayde Whittingham-Dowd ◽  
James Tollitt ◽  
...  
Keyword(s):  
Protective Efficacy ◽  
Immunoglobulin A ◽  
Clinical Disease ◽  
Cell Mediated Immunity ◽  
Complete Protection ◽  
Intranasal Route ◽  
Live Attenuated Vaccine ◽  
Safe Vaccine ◽  
Vectored Vaccine ◽  
Preclinical Animal Models

ABSTRACTThe global deployment of an effective and safe vaccine is currently a public health priority to curtail the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we evaluated a Newcastle disease virus (NDV)-based intranasal vectored-vaccine in mice and hamsters for its immunogenicity, safety and protective efficacy in challenge studies with SARS-CoV-2. The recombinant (r)NDV-S vaccine expressing spike (S) protein of SARS-CoV-2 administrated via intranasal route in mice induced high levels of SARS-CoV-2-specific neutralizing immunoglobulin A (IgA) and IgG2a antibodies and T cell-mediated immunity. Hamsters vaccinated with two doses of vaccine showed complete protection from clinical disease including lung infection, inflammation, and pathological lesions after SARS-CoV-2 challenge. Importantly, a single or double dose of intranasal rNDV-S vaccine completely blocked SARS-CoV-2 shedding in nasal turbinate and lungs within 4 days of vaccine administration in hamsters. Taken together, intranasal administration of rNDV-S has the potential to control infection at the site of inoculation, which should prevent both the clinical disease and transmission to halt the spread of the COVID-19 pandemic.

scholarly journals Soluble Spike DNA Vaccine Provides Long-Term Protective Immunity against SARS-CoV-2 in Mice and Nonhuman Primates

Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 307
Author(s):  
Yong Bok Seo ◽  
You Suk Suh ◽  
Ji In Ryu ◽  
Hwanhee Jang ◽  
Hanseul Oh ◽  
...  
Keyword(s):  
T Cell ◽  
Nonhuman Primates ◽  
Vaccine Candidate ◽  
T Cell Responses ◽  
Neutralizing Antibody ◽  
Dependent Manner ◽  
Viral Loads ◽  
Cell Responses ◽  
Rapid Spread

The unprecedented and rapid spread of SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) has motivated the need for a rapidly producible and scalable vaccine. Here, we developed a synthetic soluble SARS-CoV-2 spike (S) DNA-based vaccine candidate, GX-19. In mice, immunization with GX-19 elicited not only S-specific systemic and pulmonary antibody responses but also Th1-biased T cell responses in a dose-dependent manner. GX-19-vaccinated nonhuman primates seroconverted rapidly and exhibited a detectable neutralizing antibody response as well as multifunctional CD4+ and CD8+ T cell responses. Notably, when the immunized nonhuman primates were challenged at 10 weeks after the last vaccination with GX-19, they had reduced viral loads in contrast to non-vaccinated primates as a control. These findings indicate that GX-19 vaccination provides a durable protective immune response and also support further development of GX-19 as a vaccine candidate for SARS-CoV-2.

scholarly journals Immunogenicity and Safety of an Inactivated Quadrivalent Influenza Vaccine Candidate: A Phase III Randomized Controlled Trial in Children

2013 ◽  
Vol 208 (4) ◽  
pp. 544-553 ◽  
Author(s):  
Joanne M. Langley ◽  
Alfonso Carmona Martinez ◽  
Archana Chatterjee ◽  
Scott A. Halperin ◽  
Shelly McNeil ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Influenza Vaccine ◽  
Vaccine Candidate ◽  
Controlled Trial ◽  
Phase Iii ◽  
Randomized Controlled ◽  
Quadrivalent Influenza Vaccine

scholarly journals Replication-Competent NYVAC-KC Yields Improved Immunogenicity to HIV-1 Antigens in Rhesus Macaques Compared to Nonreplicating NYVAC

2018 ◽  
Vol 93 (3) ◽  
Author(s):  
Karen V. Kibler ◽  
Benedikt Asbach ◽  
Beatriz Perdiguero ◽  
Juan García-Arriaza ◽  
Nicole L. Yates ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Vaccine Candidate ◽  
Rhesus Macaques ◽  
Phase Iii ◽  
Effective Vaccine ◽  
Phase Iii Clinical Trial ◽  
Boost Regimen ◽  
Clade C ◽  
The One ◽  
Hiv 1

ABSTRACT As part of the continuing effort to develop an effective HIV vaccine, we generated a poxviral vaccine vector (previously described) designed to improve on the results of the RV144 phase III clinical trial. The construct, NYVAC-KC, is a replication-competent, attenuated recombinant of the vaccinia virus strain NYVAC. NYVAC is a vector that has been used in many previous clinical studies but is replication deficient. Here, we report a side-by-side comparison of replication-restricted NYVAC and replication-competent NYVAC-KC in a nonhuman primate study, which utilized a prime-boost regimen similar to that of RV144. NYVAC-C and NYVAC-C-KC express the HIV-1 antigens gp140, and Gag/Gag-Pol-Nef-derived virus-like particles (VLPs) from clade C and were used as the prime, with recombinant virus plus envelope protein used as the boost. In nearly every T and B cell immune assay against HIV-1, including neutralization and antibody binding, NYVAC-C-KC induced a greater immune response than NYVAC-C, indicating that replication competence in a poxvirus may improve upon the modestly successful regimen used in the RV144 clinical trial. IMPORTANCE Though the RV144 phase III clinical trial showed promise that an effective vaccine against HIV-1 is possible, a successful vaccine will require improvement over the vaccine candidate (ALVAC) used in the RV144 study. With that goal in mind, we have tested in nonhuman primates an attenuated but replication-competent vector, NYVAC-KC, in direct comparison to its parental vector, NYVAC, which is replication restricted in human cells, similar to the ALVAC vector used in RV144. We have utilized a prime-boost regimen for administration of the vaccine candidate that is similar to the one used in the RV144 study. The results of this study indicate that a replication-competent poxvirus vector may improve upon the effectiveness of the RV144 clinical trial vaccine candidate.

Bi-functional sterically hindered phenol lipid-based delivery systems as potential multi-target agents against Alzheimer's disease via an intranasal route

Nanoscale ◽  
2020 ◽  
Vol 12 (25) ◽  
pp. 13757-13770
Author(s):  
Evgenia A. Burilova ◽  
Tatiana N. Pashirova ◽  
Irina V. Zueva ◽  
Elmira M. Gibadullina ◽  
Sofya V. Lushchekina ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Intranasal Administration ◽  
Delivery Systems ◽  
Sterically Hindered Phenols ◽  
Intranasal Route ◽  
Sterically Hindered Phenol ◽  
Hindered Phenols ◽  
Hindered Phenol ◽  
Sterically Hindered

New lipid-based nanomaterials based on sterically hindered phenols were developed as potential drugs against Alzheimer's disease via intranasal administration.

The Intranasal Route as an Alternative Method of Medication Administration

2018 ◽  
Vol 38 (5) ◽  
pp. 26-31 ◽  
Author(s):  
Calvin Tucker ◽  
Lyn Tucker ◽  
Kyle Brown
Keyword(s):  
Intranasal Administration ◽  
Pediatric Patients ◽  
Medication Administration ◽  
Intravenous Route ◽  
Appropriate Use ◽  
Intranasal Route ◽  
Superior Efficacy ◽  
Invasive Method ◽  
Correct Technique ◽  
Intranasal Drug Administration

Intranasal drug administration is a less invasive method of drug delivery that is easily accessible for adult and pediatric patients. Medications administered by the intranasal route have efficacy comparable to intravenous administration and typically have superior efficacy to subcutaneous or intramuscular routes. The intranasal route is beneficial in emergent situations when the intravenous route is not available. The intranasal route is safe and effective in various indications, and therapeutic systemic concentrations of medication can be attained via this route. As the evidence for and comfort with intranasal administration continue to grow, guidance on correct technique, medications, and dosing is vital for appropriate use. This article reviews the process and practices of appropriate intranasal medication administration.

scholarly journals Lipoprotein-Associated Phospholipase A2 (Lp-PLA2): A Novel and Promising Biomarker for Cardiovascular Risks Assessment

2013 ◽  
Vol 34 (5) ◽  
pp. 323-331 ◽  
Author(s):  
Anping Cai ◽  
Dongdan Zheng ◽  
Ruofeng Qiu ◽  
Weiyi Mai ◽  
Yingling Zhou
Keyword(s):  
Phospholipase A2 ◽  
Clinical Studies ◽  
Vascular Inflammation ◽  
Specific Inhibitor ◽  
Basic Research ◽  
Phase Iii ◽  
Cardiovascular Risks ◽  
Two Phase ◽  
Preclinical Trials ◽  
Risks Assessment

Atherosclerosis and its manifestations namely cardiovascular diseases (CVD) are still the leading cause of morbidity and mortality worldwide. Although intensified interventions have been applied, the residual cardiovascular (CV) risks are still very high. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a novel and unique biomarker highly specific for vascular inflammation and atherosclerosis. Both pro-atherogenic property of Lp-PLA2and positive correlation with CV events have already been demonstrated by a large number of scientific and clinical studies. Currently, in the Adult Treatment Panel III (ATP III) guideline, Lp-PLA2has been recommended as an adjunct to traditional risk factors in assessing future CV risks. Encouragingly, darapladib, an orally Lp-PLA2specific inhibitor, has been tested in basic research and preclinical trials and the outcomes are quite striking. Additionally, there are two phase III ongoing clinical trials in evaluating the efficacy and safety of darapladib on cardiovascular outcomes. With regard to the potential values of Lp-PLA2in risk stratification, therapeutic regimen establishment and prognosis evaluation in patients with moderate or high risk, our present review is going to summarize the relevant data about the bio-chemical characteristics of Lp-PLA2, the actions of Lp-PLA2on atherosclerosis and the results of Lp-PLA2in scientific research and clinical studies.

Treatment of Migraine Attacks with Intranasal Alniditan: An Open Study

Cephalalgia ◽  
2001 ◽  
Vol 21 (2) ◽  
pp. 140-144 ◽  
Author(s):  
HC Diener ◽  
P Louis ◽  
R Schellens ◽  
F De Beukelaar ◽  
Keyword(s):  
Open Study ◽  
Migraine Headache ◽  
Intranasal Administration ◽  
Receptor Agonist ◽  
Intranasal Route ◽  
Taste Disturbance ◽  
Migraine Headaches ◽  
Nasal Irritation ◽  
Severe Intensity ◽  
Time To Onset

In this open phase-II clinical tolerability trial 17 neurologists enrolled a total of 112 patients and instructed them to administer a maximum of two doses of intranasal alniditan, a 5-HT1B/D receptor agonist, for the treatment of three consecutive migraine attacks of moderate to severe intensity. A second dose of the trial medication was allowed within 1–24 h after the first administration. At 1 h after intranasal administration, 70/103 (68%) patients had responded to treatment (reduction from severe or moderate headache before treatment to mild or no headache) after their first migraine attack, 65/94 (69%) after their second and 52/75 (71%) after their third. In 187/270 (69%) of all attacks, patients were considered responders at 1 h. The median time to onset of effect was 30 min. The migraine headache recurred in 44% (attack 1), 55% (attack 2) and 44% (attack 3) after 4–5 h. Sixty-eight per cent of the patients reported nasal irritation, 19% taste disturbance and 44% throat irritation. Alniditan 2 mg, administered via the intranasal route, was effective in relieving migraine headaches in over two-thirds of the patients at 1 h.

scholarly journals Bioavailability of butorphanol after intranasal administration to horses

2020 ◽  
Vol 23 (4) ◽  
pp. 443-447
Author(s):  
V. Ferreira ◽  
M. Velloso ◽  
M. Landoni
Keyword(s):  
Intranasal Administration ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Plasma Concentrations ◽  
Volume Of Distribution ◽  
Intravenous Route ◽  
Liquid Chromatography Mass Spectrometry ◽  
Intranasal Route ◽  
Predetermined Time ◽  
Mass Spectrometry Assay

The aim of the present study was to describe butorphanol pharmacokinetics and bioavailability following intranasal administration to horses. Six adult horses received 0.05 mg/kg butorphanol, in a randomised crossover design, by either intravenous or intranasal route. Plasma concentrations of butorphanol were measured at predetermined time points using liquid chromatography/mass spectrometry assay. After intravenous injection, mean ±SD butorphanol steady-state volume of distribution and clearance was 3.20 ± 1.77 l/kg and 3.18 ± 1.47 L/kg/h, respectively. Terminal half-lives for butorphanol after intravenous and intranasal administrations were 0.68 ± 0.17 h and 1.79 ± 1.43 h. For intranasal administration, absorption half-life and peak plasma concentration were 0.43 ± 0.33 h and 1.95 ± 1.7 ng/mL, respectively. Bioavailability was 54.45 ± 20.09%. Intranasal butorphanol administration in horses is practical, not stressful and well tolerated. Therefore, it might be a substitute to the intravenous route in adult horses

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