Sue Charlton presents analytical methods for assessing the efficacy of anthrax vaccines. A number of assays have been developed including macrophage cell lysis assays, toxin and antibody ELISAs, toxin neutralization assays, mouse potency tests, and rabbit challenge models. These assays have been used to evaluate traditional and novel anthrax vaccines and generate data to support regulatory submissions. Clinical studies on humans have also evaluated the immune response to booster vaccinations and how it is affected by time since the last booster. The various efficacy tests together provide a toolbox to characterize different anthrax vaccines and their ability to induce a protective immune response.
The lecture describes the performance and presentation of the antibiograms by the hospitals based upon recommendations of CLSI and shows experience of some of our MOH hospitals with the advantages and pitfalls in them.
Since the first EGFR targeting antibody panitumumab (Vectibix) from humanized mice has obtained regulatory approval in 2005, dozens of additional transgenic mouse-derived mAbs have entered human clinical testing, i.e., CD20 (Ofatumumab), CD4 (Zanolimumab), CD70, etc. These genetically "humanized" animals have become one of the most powerful strategies for therapeutic/ diagnostic antibody development, which is now the fastest growing group of mAb drugs in clinical trials currently.
The lecture describes the performance and presentation of the antibiograms by the hospitals based upon recommendations of CLSI and shows experience of some of our MOH hospitals with the advantages and pitfalls in them.
Since the first EGFR targeting antibody panitumumab (Vectibix) from humanized mice has obtained regulatory approval in 2005, dozens of additional transgenic mouse-derived mAbs have entered human clinical testing, i.e., CD20 (Ofatumumab), CD4 (Zanolimumab), CD70, etc. These genetically "humanized" animals have become one of the most powerful strategies for therapeutic/ diagnostic antibody development, which is now the fastest growing group of mAb drugs in clinical trials currently.
Evaluation of anti-HIV potential in selected medicinal plantsTitas Mallick
Acquired immunodeficiency syndrome (AIDS) is a global pandemic. Since its discovery >36.9 million people have lost their lives. Although highly active antiretroviral therapy (HAART) has been successful in significantly lowering viral titers as HIV-1 integrates into host genome it is not targeted by HAART and hence not eliminated. Therefore, the virus rebounds on discontinuation of drugs. Hence, patients are likely to take therapy for a lifetime and long-term drug treatment leads to severe drug-induced toxicity and also the emergence of multidrug-resistant viruses. It is pertinent to mention that the rate of emergence of resistant strains of HIV-1 is much greater than the rate of new drug development. Hence there is an urgent need to develop new strategies to tackle HIV-1 and emerging resistant strains.
Compounds from plant origin have enormous potential in terms of their incomparable structural diversity and plant kingdom needs to be explored for anti-HIV-1 molecules. In the present study medicinal plants namely Catharanthusroseus, Ocimumgratissimum, Mangifera sp., Tinospora sp., Solanum sp., Swertia bimaculata were evaluated for their anti-HIV-1 activity in cell culture. Crude extracts of the dried plants were prepared using solvents viz. hexane, chloroform, and methanol or Ethyl Acetate. Extracts were dissolved in DMSO and filter sterilized and screened for anti-HIV-1 activity using pseudotyped HIV-1 virus with GFP (Green Fluorescent Protein) reporter system. Prior cytotoxic concentrations 50 (CC50) of each extract was determined and all the extracts used in the present study were below their respective CC50 concentrations.
The significant anti-HIV-1 activity was observed in methanolic extracts of Ocimum gratissimum, ethyl Acetate extracts of Tinospora sp. Further fractionation of Ocimum gratissimum showed anti-HIV-1 activity in- E3M7 1 fraction.
Mario H. Skiadopoulos Presentation on "Evaluation of the Antibody Threshold o...Matthew Kirkby
Mario H. Skiadopoulos Presentation on "Evaluation of the Antibody Threshold of Protection Conferred by a NextGeneration Anthrax Vaccine Candidate Adjuvanted with the Immunostimulatory CPG 7909 TLR9 Agonist" at Biology of Anthrax, Tampa 2016
The purpose of this review is to provide veterinarians with key facts and information relevant to serological testing of individual dogs and cats in the clinical setting. Specifically, this paper addresses the role of antibody testing for the core, vaccine-preventable diseases canine distemper virus, canine and feline parvovirus, and canine adenovirus.
Dr. Sid Thakur - Antimicrobial Resistance: Do We Know Everything?John Blue
Antimicrobial Resistance: Do We Know Everything? - Dr. Sid Thakur, Assistant Professor, North Carolina State University, from the 2013 NIAA Merging Values and Technology conference, April 15-17, 2013, Louisville, KY, USA.
More presentations at http://www.trufflemedia.com/agmedia/conference/2013-niaa-merging-values-and-technology
This presentation is about lab diagnosis of tuberculosis. It highlights use of currently available diagnostic methods in identifying pulmonary and extrapulmonary tuberculosis.
Learn about novel cell-based assays that enable improved immunotherapy drug development. See case studies utilizing checkpoint receptors such as PD-1, VISTA, and NIK.
Evaluation of anti-HIV potential in selected medicinal plantsTitas Mallick
Acquired immunodeficiency syndrome (AIDS) is a global pandemic. Since its discovery >36.9 million people have lost their lives. Although highly active antiretroviral therapy (HAART) has been successful in significantly lowering viral titers as HIV-1 integrates into host genome it is not targeted by HAART and hence not eliminated. Therefore, the virus rebounds on discontinuation of drugs. Hence, patients are likely to take therapy for a lifetime and long-term drug treatment leads to severe drug-induced toxicity and also the emergence of multidrug-resistant viruses. It is pertinent to mention that the rate of emergence of resistant strains of HIV-1 is much greater than the rate of new drug development. Hence there is an urgent need to develop new strategies to tackle HIV-1 and emerging resistant strains.
Compounds from plant origin have enormous potential in terms of their incomparable structural diversity and plant kingdom needs to be explored for anti-HIV-1 molecules. In the present study medicinal plants namely Catharanthusroseus, Ocimumgratissimum, Mangifera sp., Tinospora sp., Solanum sp., Swertia bimaculata were evaluated for their anti-HIV-1 activity in cell culture. Crude extracts of the dried plants were prepared using solvents viz. hexane, chloroform, and methanol or Ethyl Acetate. Extracts were dissolved in DMSO and filter sterilized and screened for anti-HIV-1 activity using pseudotyped HIV-1 virus with GFP (Green Fluorescent Protein) reporter system. Prior cytotoxic concentrations 50 (CC50) of each extract was determined and all the extracts used in the present study were below their respective CC50 concentrations.
The significant anti-HIV-1 activity was observed in methanolic extracts of Ocimum gratissimum, ethyl Acetate extracts of Tinospora sp. Further fractionation of Ocimum gratissimum showed anti-HIV-1 activity in- E3M7 1 fraction.
Mario H. Skiadopoulos Presentation on "Evaluation of the Antibody Threshold o...Matthew Kirkby
Mario H. Skiadopoulos Presentation on "Evaluation of the Antibody Threshold of Protection Conferred by a NextGeneration Anthrax Vaccine Candidate Adjuvanted with the Immunostimulatory CPG 7909 TLR9 Agonist" at Biology of Anthrax, Tampa 2016
The purpose of this review is to provide veterinarians with key facts and information relevant to serological testing of individual dogs and cats in the clinical setting. Specifically, this paper addresses the role of antibody testing for the core, vaccine-preventable diseases canine distemper virus, canine and feline parvovirus, and canine adenovirus.
Dr. Sid Thakur - Antimicrobial Resistance: Do We Know Everything?John Blue
Antimicrobial Resistance: Do We Know Everything? - Dr. Sid Thakur, Assistant Professor, North Carolina State University, from the 2013 NIAA Merging Values and Technology conference, April 15-17, 2013, Louisville, KY, USA.
More presentations at http://www.trufflemedia.com/agmedia/conference/2013-niaa-merging-values-and-technology
This presentation is about lab diagnosis of tuberculosis. It highlights use of currently available diagnostic methods in identifying pulmonary and extrapulmonary tuberculosis.
Learn about novel cell-based assays that enable improved immunotherapy drug development. See case studies utilizing checkpoint receptors such as PD-1, VISTA, and NIK.
Identification of antibiotic resistance genes in Klebsiella pneumoniae isolat...QIAGEN
Antibiotic resistant strains of pathogenic bacteria are a growing worldwide health problem. To effectively combat the spread of difficult-to-treat bacterial infections, rapid surveillance methods for detection of antibiotic resistance genes is required to monitor both bacterial isolates and metagenomic samples. Additionally, identification of potential new sources for different antibiotic resistance genes is critical. Both of these goals require tools that can be used for profiling of antibiotic resistance genes from various types of samples. Real-time PCR has proven to be effective for the detection of antibiotic resistance genes. Using PCR array technology, simultaneous detection of 87 prevalent and important antibiotic resistance genes is possible and should prove to be an effective method for antibiotic resistance monitoring. This allows for a more comprehensive profiling of antibiotic resistance genes than is possible using individual PCR assays.
Novel research aimed at finding a cure for AIDS requires animal models responding to human antiretroviral drugs. However, there have been few antiretrovirals cross-active against the simian viruses. In this study, we expanded the arsenal of drugs active against the simian retrovirus SIVmac251 and showed that this virus is inhibited by the protease inhibitor, darunavir, and the CCR5 blocker, maraviroc. Administration of these two drugs in combination with the reverse transcriptase inhibitors, tenofovir and emtricitabine, and the integrase inhibitor, raltegravir, resulted in prolonged plasma viral loads below assay detection limits, and, surprisingly, restricted the viral reservoir, a marker of which is viral DNA. We then decided to employ this multidrug regimen (termed “highly intensified ART”) in order to increase the potency of a previous strategy based on the gold drug auranofin, which recently proved able to restrict the viral reservoir in vivo. A short course of highly intensified ART following the previous treatment resulted, upon therapy suspension, in a remarkably spontaneous control of the infection, that may pave the way to a persistent suppression of viremia in the absence of ART. These results corroborate the robustness of the macaque AIDS model as a vanguard for potentially future treatments for HIV in humans.
The effect of chemotherapy on the serological respons of patients with schist...Alim A-H Yacoub Lovers
Yacoub AA, Lillywhite J. The effect of chemotherapy on the serological response of patients with schistosoma haematobium infection using the Enzyme linked immunosorbent assay. Journal of Faculty of Medicine-Baghdad 1985;27(3):19-29.
Earliest Galaxies in the JADES Origins Field: Luminosity Function and Cosmic ...Sérgio Sacani
We characterize the earliest galaxy population in the JADES Origins Field (JOF), the deepest
imaging field observed with JWST. We make use of the ancillary Hubble optical images (5 filters
spanning 0.4−0.9µm) and novel JWST images with 14 filters spanning 0.8−5µm, including 7 mediumband filters, and reaching total exposure times of up to 46 hours per filter. We combine all our data
at > 2.3µm to construct an ultradeep image, reaching as deep as ≈ 31.4 AB mag in the stack and
30.3-31.0 AB mag (5σ, r = 0.1” circular aperture) in individual filters. We measure photometric
redshifts and use robust selection criteria to identify a sample of eight galaxy candidates at redshifts
z = 11.5 − 15. These objects show compact half-light radii of R1/2 ∼ 50 − 200pc, stellar masses of
M⋆ ∼ 107−108M⊙, and star-formation rates of SFR ∼ 0.1−1 M⊙ yr−1
. Our search finds no candidates
at 15 < z < 20, placing upper limits at these redshifts. We develop a forward modeling approach to
infer the properties of the evolving luminosity function without binning in redshift or luminosity that
marginalizes over the photometric redshift uncertainty of our candidate galaxies and incorporates the
impact of non-detections. We find a z = 12 luminosity function in good agreement with prior results,
and that the luminosity function normalization and UV luminosity density decline by a factor of ∼ 2.5
from z = 12 to z = 14. We discuss the possible implications of our results in the context of theoretical
models for evolution of the dark matter halo mass function.
Richard's aventures in two entangled wonderlandsRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
Toxic effects of heavy metals : Lead and Arsenicsanjana502982
Heavy metals are naturally occuring metallic chemical elements that have relatively high density, and are toxic at even low concentrations. All toxic metals are termed as heavy metals irrespective of their atomic mass and density, eg. arsenic, lead, mercury, cadmium, thallium, chromium, etc.
Observation of Io’s Resurfacing via Plume Deposition Using Ground-based Adapt...Sérgio Sacani
Since volcanic activity was first discovered on Io from Voyager images in 1979, changes
on Io’s surface have been monitored from both spacecraft and ground-based telescopes.
Here, we present the highest spatial resolution images of Io ever obtained from a groundbased telescope. These images, acquired by the SHARK-VIS instrument on the Large
Binocular Telescope, show evidence of a major resurfacing event on Io’s trailing hemisphere. When compared to the most recent spacecraft images, the SHARK-VIS images
show that a plume deposit from a powerful eruption at Pillan Patera has covered part
of the long-lived Pele plume deposit. Although this type of resurfacing event may be common on Io, few have been detected due to the rarity of spacecraft visits and the previously low spatial resolution available from Earth-based telescopes. The SHARK-VIS instrument ushers in a new era of high resolution imaging of Io’s surface using adaptive
optics at visible wavelengths.
hematic appreciation test is a psychological assessment tool used to measure an individual's appreciation and understanding of specific themes or topics. This test helps to evaluate an individual's ability to connect different ideas and concepts within a given theme, as well as their overall comprehension and interpretation skills. The results of the test can provide valuable insights into an individual's cognitive abilities, creativity, and critical thinking skills
Deep Behavioral Phenotyping in Systems Neuroscience for Functional Atlasing a...Ana Luísa Pinho
Functional Magnetic Resonance Imaging (fMRI) provides means to characterize brain activations in response to behavior. However, cognitive neuroscience has been limited to group-level effects referring to the performance of specific tasks. To obtain the functional profile of elementary cognitive mechanisms, the combination of brain responses to many tasks is required. Yet, to date, both structural atlases and parcellation-based activations do not fully account for cognitive function and still present several limitations. Further, they do not adapt overall to individual characteristics. In this talk, I will give an account of deep-behavioral phenotyping strategies, namely data-driven methods in large task-fMRI datasets, to optimize functional brain-data collection and improve inference of effects-of-interest related to mental processes. Key to this approach is the employment of fast multi-functional paradigms rich on features that can be well parametrized and, consequently, facilitate the creation of psycho-physiological constructs to be modelled with imaging data. Particular emphasis will be given to music stimuli when studying high-order cognitive mechanisms, due to their ecological nature and quality to enable complex behavior compounded by discrete entities. I will also discuss how deep-behavioral phenotyping and individualized models applied to neuroimaging data can better account for the subject-specific organization of domain-general cognitive systems in the human brain. Finally, the accumulation of functional brain signatures brings the possibility to clarify relationships among tasks and create a univocal link between brain systems and mental functions through: (1) the development of ontologies proposing an organization of cognitive processes; and (2) brain-network taxonomies describing functional specialization. To this end, tools to improve commensurability in cognitive science are necessary, such as public repositories, ontology-based platforms and automated meta-analysis tools. I will thus discuss some brain-atlasing resources currently under development, and their applicability in cognitive as well as clinical neuroscience.
ESR spectroscopy in liquid food and beverages.pptxPRIYANKA PATEL
With increasing population, people need to rely on packaged food stuffs. Packaging of food materials requires the preservation of food. There are various methods for the treatment of food to preserve them and irradiation treatment of food is one of them. It is the most common and the most harmless method for the food preservation as it does not alter the necessary micronutrients of food materials. Although irradiated food doesn’t cause any harm to the human health but still the quality assessment of food is required to provide consumers with necessary information about the food. ESR spectroscopy is the most sophisticated way to investigate the quality of the food and the free radicals induced during the processing of the food. ESR spin trapping technique is useful for the detection of highly unstable radicals in the food. The antioxidant capability of liquid food and beverages in mainly performed by spin trapping technique.
ISI 2024: Application Form (Extended), Exam Date (Out), EligibilitySciAstra
The Indian Statistical Institute (ISI) has extended its application deadline for 2024 admissions to April 2. Known for its excellence in statistics and related fields, ISI offers a range of programs from Bachelor's to Junior Research Fellowships. The admission test is scheduled for May 12, 2024. Eligibility varies by program, generally requiring a background in Mathematics and English for undergraduate courses and specific degrees for postgraduate and research positions. Application fees are ₹1500 for male general category applicants and ₹1000 for females. Applications are open to Indian and OCI candidates.
Professional air quality monitoring systems provide immediate, on-site data for analysis, compliance, and decision-making.
Monitor common gases, weather parameters, particulates.
Seminar of U.V. Spectroscopy by SAMIR PANDASAMIR PANDA
Spectroscopy is a branch of science dealing the study of interaction of electromagnetic radiation with matter.
Ultraviolet-visible spectroscopy refers to absorption spectroscopy or reflect spectroscopy in the UV-VIS spectral region.
Ultraviolet-visible spectroscopy is an analytical method that can measure the amount of light received by the analyte.
Nutraceutical market, scope and growth: Herbal drug technologyLokesh Patil
As consumer awareness of health and wellness rises, the nutraceutical market—which includes goods like functional meals, drinks, and dietary supplements that provide health advantages beyond basic nutrition—is growing significantly. As healthcare expenses rise, the population ages, and people want natural and preventative health solutions more and more, this industry is increasing quickly. Further driving market expansion are product formulation innovations and the use of cutting-edge technology for customized nutrition. With its worldwide reach, the nutraceutical industry is expected to keep growing and provide significant chances for research and investment in a number of categories, including vitamins, minerals, probiotics, and herbal supplements.
ANAMOLOUS SECONDARY GROWTH IN DICOT ROOTS.pptxRASHMI M G
Abnormal or anomalous secondary growth in plants. It defines secondary growth as an increase in plant girth due to vascular cambium or cork cambium. Anomalous secondary growth does not follow the normal pattern of a single vascular cambium producing xylem internally and phloem externally.
2. Abstract
There are currently two anthrax vaccines licensed for human use; the UK
anthrax vaccine precipitated and the US BioThrax anthrax vaccine
adsorbed. A number of second and third generation vaccines are also under
development.
We have developed a tool box of in vivo and in vitro tests to evaluate the
efficacy of traditional and novel vaccines. The tests include macrophage cell
lysis, antigen and antibody ELISAs for the three toxin components, a FRET
assay for LF activity, lethal toxin neutralisation, mouse potency assays and
rabbit efficacy challenge model. The assays (except for FRET) have been
validated and data generated used to support regulatory submissions.
These tests have been used to characterise a number of vaccines.
2 Efficacy Assessment of Anthrax Vaccines
3. Outline of talk
Anthrax vaccines
Vaccine efficacy
• Efficacy vs potency?
• Efficacy and the product lifecycle
• Issues
Analytical methods to support efficacy testing of anthrax vaccines
Example data
Conclusions
3 Efficacy Assessment of Anthrax Vaccines
5. Vaccine efficacy…..what is it?
“The percentage reduction in disease incidence in a
vaccinated group compared to an unvaccinated group”
“Efficacy is best measured in a double-blind,
randomized, controlled trials”
Potency testing is performed to demonstrate the
capacity of the product to confer protective immunity
5 Efficacy Assessment of Anthrax Vaccines
6. Efficacy testing and the product
(vaccine) lifecycle
6 Efficacy Assessment of Anthrax Vaccines
Phase3
Phase2
Phase1
INDapplication
Pre-clinical
• animal models
• assay
development
• process
formulation
ValidationDiscovery
Discovery (3-5 years) Development (5-10 years)
• Develop manufacturing process
• Formulation / stability
• GMP manufacture
• Regulatory submission
• Approval for sale
• Product Support
7. Issues/Challenges
7 Efficacy Assessment of Anthrax Vaccines
Anthrax vaccines present issues that impact on regulatory compliance
& efficacy testing
• Population not normally exposed to hazard
• Field trials after accidental or hostile exposure not usually feasible
• Unusual route of infection
• Need to respond rapidly
• ‘Normal’ licensure may present unacceptable risk
– Takes too long
– Cannot conduct human challenge/protection studies
– Surrogate markers (correlates of protection)?
• Phase III clinical trials not possible
• Animal rule
• Combination vaccines
9. Anthrax toxin:
mode of action
9 Efficacy Assessment of Anthrax Vaccines
Image from Qiagen
10. 10
Plated onto flat bottomed,
96-well cell culture plates
(>70% viability) 17-19hr at 37 ºC(+/- 2 ºC),
5% CO2 (+/- 1% CO2)
J774A.1 mouse
macrophage cells
Add MTT (dye internalised by active mitochondria)
3hrs (+/- 10mins) at 37 ºC (+/- 2 ºC), 5% CO2 (+/- 1% CO2)
Add solubilising buffer (cell lysis and solubilisation of MTT)
1hr (+/- 10mins) at 37 ºC (+/- 2 ºC), 5% CO2 (+/- 1% CO2)
Read plates at 570nm
Shake for 30mins
The reference curve is
used as a control to
monitor assay
performance
Dilute 2 fold
Cells >80% confluent
Efficacy Assessment of Anthrax Vaccines
Macrophage Cell LysisAssay
10
11. Dilution
1 10 100 1000 10000
0
0.5
1
1.5
Graph#1
4-P Fit: y = (A - D)/( 1 + (x/C)^B ) + D: A B C D R^2
Plot#1 (ReferenceP1: Dilution vs Values) 0.108 2.54 45 1.36 0.996
Plot#2 (Sample 1: Dilution vs Values) 0.0995 3.72 55.3 1.35 0.995
Plot#3 (Sample 2: Dilution vs Values) 0.114 3.61 70.6 1.35 0.997
Plot#4 (Sample 3: Dilution vs Values) 0.104 3.33 74.7 1.35 0.998
Plot#5 (Sample 4: Dilution vs Values) 0.115 4.07 103 1.32 0.999
__________
Curve Fit Option - Fixed Weight Value
11 Efficacy Assessment of Anthrax Vaccines
MCLA– generation of a reportable value
11
12. Toxin NeutralisationAssay (TNA)
Functional ability of antisera, containing antibodies to anthrax
lethal toxin components (PA and/or LF), to specifically
protect J774A.1 cells against Bacillus anthracis lethal toxin
cytotoxicity
Characterisation of the immune response to anthrax
vaccination – human, mouse, rabbit, NHP and guinea pig
12 Efficacy Assessment of Anthrax Vaccines12
13. Toxin Neutralisation Assay Format
Prepare dilutions of test sera
Add to LT (1µg/ml rPA and 0.2µg/ml rLF) and
pre-incubate (30mins ±5mins)
Add to cells (>80% confluent)
Add MTT (dye internalised by active mitochondria)
Add 100 μl/well solubilising buffer
(cell lysis and solubilisation of MTT)
Read plates at 570nm
Shake for 30mins (±5mins)
17- 20 hrs
37 ºC (±2ºC), 5% CO2 (±1%)
9x104 cells/well
(>70% viability)
J774A.1
Day 1
(DMEM, 10%FBS,
L-Glutamine, Pen/Strep)
1 2 3 4 5 6 7 8 9 10 11 12
A-
H
QC
(1)
T1
(1)
T2
(1)
Ref
(1)
T3
(1)
T4
(1)
T1
(2)
T2
(2)
Ref
(2)
T3
(2)
T4
(2)
QC
(2)
3hrs (±5min) 37 ºC (±2ºC), 5% CO2 (±1%)
1hrs (±5min) 37 ºC (±2ºC), 5% CO2 (±1%)
13 Efficacy Assessment of Anthrax Vaccines
14. TNA– generation of a reportable value
14
Picture of NF50
Dilution
OD
Efficacy Assessment of Anthrax Vaccines
15. Rabbit study data
15 Efficacy Assessment of Anthrax Vaccines
14121086420
100
80
60
40
20
0
Days-to-Death
Percent
*
*
2.09
Median
Table of Statistics
1
2
3
Group
Survival Plot for Days to death
Censoring Column in Censoring
Actuarial Method
16. Mouse potency test (MPT)
16 Efficacy Assessment of Anthrax Vaccines
Immunise
mice
Collect
serum
Analyse in
TNA
Determine
potency
relative to
reference
17. 17 Efficacy Assessment of Anthrax Vaccines
Mouse Potency Test
• GMP compliant, validated relative potency (RP) assay to replace
challenge assays for release and stability testing of Anthrax Vaccines.
• The in vivo phase, where mice are vaccinated on Days 0 and 14 with
the prepared doses and bled on Day 28.
• The in vitro phase, where mouse serum is tested in the mouse Toxin
Neutralisation Assay (mTNA).
• A dose dilution series is used, with 10 CD1 mice per dose for the test
batches and reference batch.
• The dose response of the test batches is compared to the reference
batch generating a relative potency (RP) value.
19. Human clinical study:
Assessment of the effect of priorAVPvaccination on the immune
response toboosterAVPvaccination.
• GroupA– received annual boosters as per schedule
• Group B – delayed booster recipients (not receivedAVPfor at
least 2 years)
• Subjects received booster on day 1
• Blood samples taken on days 1, 8, 15, 29 and 120
• anti-PA, anti-LF, anti-EF IgG
• TNA
19 Efficacy Assessment of Anthrax Vaccines
22. TNAresponses – time since last booster
22 Efficacy Assessment of Anthrax Vaccines
23. Conclusions
23 Efficacy Assessment of Anthrax Vaccines
Established GUP & PEP protocols in rabbits and NHPs
• Primary endpoint is survival
• Immune responses (ELISA & TNA)
• Bacterial and spore counts in blood and tissues
• Clinical parameters
• Time to death
An assay “tool box” is required to support efficacy
studies
• Toxin quantitation (ELISA, MSD)
• Toxin activity (MCLA)
24. Acknowledgments
• Bassam Hallis
• Kelly Thomas
• Hannah Cuthbertson
• Emily Hughes
• Lorna McInroy
• Debbie Powell
• Pamela Proud
• Chris Neil
• Kim Steeds
24 Efficacy Assessment of Anthrax Vaccines
• Mary Matheson
• Anna England
• Simon Funnell
• Irene Taylor
• Graham Hatch
• Hugh Dyson (DSTL)