Antibiotic and Antibacterial Vaccine Development Services · B0105 Post-antibiotic Effect (PAE): The post-antibiotic effect (PAE) is an important pharmacodynamics (PD) parameter that

www.SouthernResearch.org/Drug-Development

06/01/18

Antibiotic and Antibacterial Vaccine Development Services


Contents

Why choose Southern Research? ................................................................................................................. 4

in vitro Testing Services................................................................................................................................ 5

B0101 Minimum Inhibitory Concentration (MIC): ........................................................................................ 5

B0102 Minimum Bactericidal Concentration (MBC): .................................................................................... 5

B0103 Time-kill Assay: .................................................................................................................................. 5

B0104 Resistance Frequency Determination: ............................................................................................... 5

B0105 Post-antibiotic Effect (PAE): ............................................................................................................... 6

B0106 Serum and B0107 Protein Sensitivity: ............................................................................................... 6

B0108 Serum and B0109 Protein Binding: .................................................................................................... 6

B0110 Plasma and B0111 Microsome Stability: ........................................................................................... 6

B0112 Synergy Testing: ................................................................................................................................. 7

B0113 Minimum Biofilm Inhibition Concentration (MBIC): .......................................................................... 7

B0114 Minimum Biofilm Eradication Concentration (MBEC): ...................................................................... 7

B0115 Minimum Inhibitory Concentration 90% (MIC 90): ............................................................................. 8

B0116 Opsonophagocytic Killing Assay (OPKA): ........................................................................................... 8

B0117 Opsonophagocytic Uptake Assay (OPUA): ......................................................................................... 8

B0118 Serum Bactericidal Activity (SBA): ..................................................................................................... 8

in vivo Testing ............................................................................................................................................... 9

B0201 Maximum tolerated dose (MTD): ...................................................................................................... 9

B0202 Dose Range Finding (DRF): ................................................................................................................. 9

B0203 Pharmacokinetic Profiling (PK): ......................................................................................................... 9

B0204 Bioavailability: .................................................................................................................................... 9

B0205 Neutropenic Mouse Thigh (NMTh): ................................................................................................. 10

B0206 Neutropenic Mouse Lung (NMLu): .................................................................................................. 10

B0207 Acute Murine Sepsis/Peritonitis: ..................................................................................................... 10

B0208 Chronic Murine Sepsis (Cecal Ligation and Puncture): .................................................................... 10

B0209 Murine Acute Pneumonia: ............................................................................................................... 11

B0210 Skin Infection – Tape-stripping: ....................................................................................................... 11

B0211 Surgical Site Infection—Suture: ....................................................................................................... 11


B0212 Wound Infection—Punch Biopsy: .................................................................................................... 11

B0213 Transcervical Chlamydia Persistence: .............................................................................................. 12

B0214 Pharmacodynamic Dose Fractionation: ........................................................................................... 12

B0215 in vivo Resistance Monitoring: ......................................................................................................... 12

B0216 in vivo Post-Antibiotic Effect (PAE): ................................................................................................. 12

B0217 Vaccine Immunogenicity Evaluation: ............................................................................................... 13

IND-Enabling Toxicology: ............................................................................................................................ 13

Clinical Trial Endpoint Analysis .................................................................................................................. 14

B0301 Opsonophagocytic Killing Assay (OPKA): ......................................................................................... 14

B0302 Opsonophagocytic Uptake Assay (OPUA): ...................................................................................... 14

B0303 Serum Bactericidal Activity (SBA): ................................................................................................... 14

Additional Bioanalytical and Immunological Endpoint Assays: .................................................................. 14

Southern Research


What our clients are saying

“Everything has been excellent. Communication between my company and the SR group has been great. They have been very responsive and have expertly solved all issues we’ve encountered. The SR group has performed exceptionally well! We hope to work with them again.”

“I’m very impressed with the SR study director. He is very responsive and thoughtful. I very much enjoy working with him.”

“Thanks for all of your efforts. The study, although very challenging, really went a long way towards us obtaining clearance to commence our Phase I trial.”

Why choose Southern Research? Founded in 1941 in Birmingham, Alabama, Southern Research is a scientific and engineering contract

research organization that conducts drug discovery and development, environmental and occupational

hazard characterization, advanced engineering research in materials and systems development, and

energy and environmental technologies research. SR supports clients and partners in the

pharmaceutical, agrochemical, biotechnology, defense, aerospace, environmental, and energy

industries. We deliver quality results and a quality experience.

That means we’re rapid, reliable, and responsive. With over 50 years of experience, we recognized that

no two test articles are ever the same. That’s why our approach has always been, and still is, to focus on

each client’s individual needs. Our scientists and study directors will take the time to understand your

program and the specific risks and liabilities you are concerned about. Then, after we fully understand

your needs, we will work with you to develop the most appropriate, regulatory-compliant testing plan.

But the quality experience doesn’t stop when the study protocol is signed. Our nationally recognized

scientific and quality assurance teams will execute the plan to our exacting operational standards,

ensuring we generate the highest quality data and reports. Throughout the study, be it one day or two

years, your Southern Research study director will be readily accessible and will proactively communicate

the status of your project.

Services

In vitro antibacterial, antiviral and anticancer screening

Infectious disease and cancer animal efficacy models

Pharmacokinetics/Toxicokinetics

Immunoassay and bioanalytical chemistry

Immunogenicity and immunopotency

Vaccine neurovirulence/neuropathology

IND-enabling nonclinical toxicology

Developmental and reproductive toxicology

Neurotoxicity and neurobehavioral assessment

Clinical trial endpoint analysis

Experience

Internationally recognized infectious disease, cancer, immunoassay, and bioanalytical chemistry experts

Multiple American Board of Toxicology certified toxicologists

Multiple American College of Veterinary Pathologists certified pathologists

Multi-award winning histopathology support team

American Association for Laboratory Animal Science (AALAS) accredited technicians and managers

Nationally recognized quality assurance unit

Compliance with federal and industry regulations (ICH, OECD, EPA, FDA, USDA, OLAW, GLP)

The SR campus in downtown Bi rmingham, Alabam a.

Southern Research | in vitro Services


in vitro Testing Services

B0101 Minimum Inhibitory Concentration (MIC): The MIC is defined as the lowest concentration of compound needed to inhibit visible growth for a given

organism. It is determined following Clinical and Laboratory Standards Institute (CLSI) guidelines, as

appropriate. The MIC is reported as the lowest concentration of drug that completely inhibits growth of

the test organism. Southern Research has pre-assembled panels of test organisms to ease strain

selection including: An ESKAPE pathogen panel, an MDR panel, a CRE panel, an ESBL-panel, a respiratory

pathogen panel, a wound pathogen panel, a CF pathogen panel, an STI pathogen panel, a meningitis

panel, an endocarditis panel, and a gastroenteritis panel.

Reportable Results: Compound concentration (µg/mL)

B0102 Minimum Bactericidal Concentration (MBC): The MBC is defined as the lowest concentration of compound that achieves at least a 3 log10 reduction in

CFU compared to the initial inoculum. It is determined subsequent to MIC testing by subculturing

diluted aliquots to a solid medium for bacterial enumeration. These aliquots are taken from wells

containing compound but that fail to exhibit macroscopic growth. MBC values greater than 16 times the

MIC typically indicate bacteriostatic activity or antimicrobial tolerance.


B0103 Time-kill Assay: The time-kill or Suspension Test determines the time required for the antimicrobial agent to inactivate

the challenge test microorganism. Microbial kill is measured as a function of time and concentration.

Typically, testing is conducted over a 24-hour time period using concentrations of compound at 1-2X the

established MIC. Aliquots are plated at various time-points to determine bacterial viability.

Reportable Results: Log10 CFU v. Time

B0104 Resistance Frequency Determination: To determine the spontaneous resistance frequency, bacteria are grown to late Log phase, washed, and

plated onto agar plates containing the test article at 4 x the MIC. To determine the induced resistance

frequency, bacteria are grown to late log phase or stationary phase in sub lethal concentrations of the

test article before washing and plating. In both cases, the number of resistant colonies is divided by the

total viable cell count per plate to calculate the resistance frequency.

Reportable Results: Frequency of Resistance (resistant colonies/total viable cell count)



B0105 Post-antibiotic Effect (PAE): The post-antibiotic effect (PAE) is an important pharmacodynamics (PD) parameter that evaluates the

ability of a given test article to suppress bacterial growth after drug levels fall below the MIC. Bacteria in

the log phase of growth are exposed to 2X, 4X and 8X the MIC for 1 hour. After exposure, cells are

washed to remove the test article and suspended in broth without antibiotic. Viable bacteria are

enumerated by serial plating at hourly time points for 6-8 hours.

Reportable Results: PAE is the time (in hours) for drug exposed bacteria to increase in number by 1

log10 minus the time for non-exposed cells to increase in number by 1 log10.

B0106 Serum and B0107 Protein Sensitivity: The pharmacodynamics (PD) of antibiotics can be substantially altered due to binding to protein in

serum. To screen for this possibility, time-kill assays are performed at 2X, 5X, 10X, 20X and 50X the MIC

in media supplemented with 20 g/L human albumin (the albumin content of interstitial fluid) or

inactivated serum (50% v/v).

Reportable Results: Log10 CFU v. Time for each condition in standard media and media supplemented

with albumin or serum.

B0108 Serum and B0109 Protein Binding: Protein binding is determined by a standard dialysis method wherein the test article is suspended in a

solution containing active or inactivated human serum 50% v/v (B0108 Serum Binding) or 20 g/L or 40

g/L albumin (B0109 Protein Binding). During dialysis, the solution is allowed to equilibrate across a semi-

permeable membrane resulting in selective diffusion of unbound test article. The test article

concentration is determined in the initial samples and in the filtrates using an appropriate bioanalytical

chemistry method (transferred or developed separately) or a microbiological agar diffusion bioassay

that uses Bacillus stearothermophilus ATCC 3032 or another suitable species as a test organism.

Reportable Results: Percentage of protein binding.

B0110 Plasma and B0111 Microsome Stability: Plasma and hepatic stability play crucial roles in the ultimate efficacy of therapeutics. Test articles are

subject to degradation and modification by a wide range of enzymes in the liver and plasma. To assess

stability, the test article is mixed with plasma or liver microsomes from the target host species

(nonclinical species or human). At various time points post mixing, aliquots are extracted and analyzed

using an appropriate bioanalytical method.

Reportable Results: Half-life and Percent Parent Compound Remaining



B0112 Synergy Testing: Synergy, or combination, testing determines the interaction between two antimicrobials and the

resulting impact on the potency of each. The Fractional Inhibitory Concentration (FIC) is determined

using the following formula:

FICA + FICB = FIC FICA = MIC of compound A in combination/MIC of compound A alone FICB = MIC of compound B in combination/MIC of compound B alone

The FIC for any given combination is interpreted as follows:

Synergy = FIC < 0.5 No interaction = 0.5 < FIC < 4.0 Antagonism = FIC > 4.0

Reportable Results: Fractional Inhibitory Concentration (FIC)

B0113 Minimum Biofilm Inhibition Concentration (MBIC): Bacterial biofilms often demonstrate greater resistance to antibiotics compared with planktonic cells.

The Minimum Biofilm Inhibition Concentration (MBIC) assay is a derivative of the MIC wherein the

lowest concentration of compound needed to inhibit biofilm formation is determined via a broth

microdilution method. Briefly, the challenge bacterium is inoculated into a 96-well tissue culture plate

containing appropriate broth and two-fold dilutions of the test compound. The plates are then

incubated under conditions that promote biofilm formation. Following growth, total biomass is

measured using crystal violet dye. The MBIC is reported as the lowest concentration of drug that

completely inhibits biofilm formation.


B0114 Minimum Biofilm Eradication Concentration (MBEC): The MBEC is defined as the lowest concentration of compound needed to eradicate a pre-formed

biofilm. In this case, bacterial biofilms are formed on the surface of submerged polystyrene pegs. These

pre-formed biofilms are then transferred to a 96-well plate containing broth and two-fold dilutions of

the test compounds. After exposure for 18-24 hours at 37°C, the pegs are transferred to fresh media

without antibiotic. After an additional incubation period of 8 hours, the optical density of the medium in

these wells is measured at 650 nm. The MBEC is reported as the lowest concentration of drug that

prevents an increase in optical density of 0.05 or greater.




B0115 Minimum Inhibitory Concentration 90% (MIC 90): Where the classic MIC assay determines the minimum concentration of a test article required to inhibit

the growth of a particular isolate, the MIC50 and the MIC90 values represent the minimum concentration

of test article that is required to inhibit 50% or 90% of a population of isolates. Typically, at least 30 (and

often many more) isolates are tested, representing the full, clinically relevant phenotypic diversity of the

target species. Sothern Research maintains MIC50/90 panels for the following bacterial species:

Acinetobacter baumannii, Clostridium difficile, Klebsiella pneumonia, Neisseria gonorrhoeae,

Pseudomonas aeruginosa, Staphylococcus aureus, and Mycobacterium tuberculosis.


B0116 Opsonophagocytic Killing Assay (OPKA): Typically used as a non-clinical and clinical endpoint for the development of antibacterial vaccines or

therapeutic antibodies, the opsonophagocytic killing assay (OPKA) measures the titer of opsonic

antibody activity in sera. Briefly, the target bacterium is mixed with whole blood, polymorphonuclear

leukocytes (PMNs) or differentiated HL-60 cells and the test sera or antibody. Relative killing is

calculated as the percent difference in viable CFU after 0 and 60 minutes of exposure.

Reportable Results: Percent relative killing.

B0117 Opsonophagocytic Uptake Assay (OPUA): Typically used as a non-clinical endpoint for the development of antibacterial vaccines or therapeutic

antibodies, the opsonophagocytic uptake assay (OPUA) measures the titer of opsonic antibody activity in

sera. Briefly, a fluorescently-labeled target bacterium is mixed with polymorphonuclear leukocytes

(PMNs) or differentiated HL-60 cells and the test sera or antibody. Uptake is calculated using flow

cytometry.

Reportable Results: Percent uptake.

B0118 Serum Bactericidal Activity (SBA): The serum bactericidal assay (SBA) measures the ability of antibodies to mediate complement-

dependent pathogen killing. Log phase bacteria are mixed with serial dilutions of test serum or antibody

and an external source of complement. Following incubation, cells are washed and bacterial ATP

generation is measured in a microtiter format using a luciferase reporter. Bactericidal serum titers are

calculated as the reciprocal serum dilution necessary to obtain a 50% reduction in luminosity compared

to control wells.

Reportable Results: Bactericidal titer.

Southern Research | in vivo Services


in vivo Testing

B0201 Maximum tolerated dose (MTD): In order to properly interpret data from subsequent efficacy studies, it is necessary to form a basic

understanding of the test article toxicology and pharmacokinetics in rodents. The Maximum Tolerated

Dose (MTD) is defined as the highest dose of a test article that does not cause overt, acute toxicity.

Typically, the MTD is determined using a short duration dose escalation study that include a minimum

number of animals.

Reportable Results: Clinical Observations, Morbidity, Mortality, Weight Loss

B0202 Dose Range Finding (DRF): In order to properly interpret data from subsequent efficacy studies, it is necessary to form a basic

understanding of the test article toxicology and pharmacokinetics. The Dose Range Finding (DRF) study

is used to define the Maximum Repeatable Dose, which is critical for prolonged efficacy models such as

chronic sepsis or wound infections. In this study, three or four dose levels of the test article are

administered once daily for seven consecutive days. Afterwards, mice are euthanized and gross

necropsy and/or histopathological evaluation is used to identify acceptable dosing levels for efficacy

testing.

Reportable Results: Clinical Observations, Morbidity, Mortality, Weight Loss, Gross

Pathology, Histophathology

B0203 Pharmacokinetic Profiling (PK): Pharmacokinetic (PK) studies are used to determine the rate of test article clearance after

administration at the MTD or MRD defined above. This information is critical to proper design and

interpretation of subsequent efficacy studies. Serum concentration can be measured using an

appropriate bioanalytical assay (e.g., LC-MS/MS, ELISA, qPCR, etc.).

Reportable Results: Serum concentration, PK parameters: Tmax, Cmax, AUC, Vd, CL, T1/2, Kab

B0204 Bioavailability: Bioavailability can be measured during a PK study by adding a second treatment arm and comparing oral

or subcutaneous dosing with intravenous dosing.

Reportable Results: Systemically available fraction (plus typical PK results)



B0205 Neutropenic Mouse Thigh (NMTh): The neutropenic mouse thigh is a standard assay used to evaluate the pharmacodynamics

characteristics of a test article in vivo. Because viable but antibiotic-damaged bacteria are more

susceptible to killing by phagocytic cells, mice are rendered neutropenic for the course of the assay.

Mice are challenged with a single inoculation of bacteria into one or both thighs prior to administration

of the test article (typically two hours post challenge). At 24-hours post treatment, thighs are aseptically

removed, homogenized and plated to determine the total bacterial burden.

Reportable Results: CFU/g and Log10 CFU reduction from control group

B0206 Neutropenic Mouse Lung (NMLu): Because the pharmacokinetics of the lung compartment often differs from that of the serum and

muscle, the neutropenic mouse lung assay is used to evaluate the pharmacodynamics of a test article

during infection of the lung. Mice are rendered neutropenic for the course of the assay and are

challenged with a single intranasal inoculation of bacteria. Two hours after challenge, the test article is

administered. At 24-hours post treatment, lungs are aseptically removed, homogenized and plated to

determine the total bacterial burden.

Reportable Results: CFU/g tissue and Log10 CFU reduction from control group

B0207 Acute Murine Sepsis/Peritonitis: The acute sepsis/peritonitis model is an ideal platform to screen for initial in vivo efficacy relative to

systemic indications in an immune competent host animal. A single, high-dose challenge of bacteria is

used to generate acute bacteremia and endotoxemia. Antibacterial and control agents are administered

following challenge and blood is harvested from all animals at 12 hours post treatment. Symptoms are

recorded on a standardized scoresheet at 6 hours and 12 hours post-treatment and every 12 hours

thereafter until the end of the study. Bacterial burden in the spleen or kidney of surviving animals is

analyzed at 48-72 hours post-treatment.

Reportable Results: Survival, Clinical Score, CFU/ml blood, CFU/g tissue, Log10 CFU reduction from

control group

B0208 Chronic Murine Sepsis (Cecal Ligation and Puncture): Surgical ligation and puncture of the cecum induces a prolonged, low-level, polymicrobial septicemia.

This procedure generally leads to 80-90% mortality in untreated mice by day 5. All mice are observed

twice daily for mortality and surviving mice are weighed and scored for severity of disease symptoms

using a standardized score sheet.

Reportable Results: Survival, Clinical Score, Body Weight



B0209 Murine Acute Pneumonia: The acute pneumonia model is an ideal platform to screen for initial in vivo efficacy relative to lung

indications in an immune competent host. C57Bl/6 mice are challenged with a single dose of bacteria

delivered intranasally. Test and control articles are administered two hours after challenge. At 6- and 24-

hours after treatment, mice are euthanized and the bacterial burden in the blood and lungs are

determined by serial dilution.

Reportable Results: CFU/ml blood, CFU/g tissue, Log10 CFU reduction from control group

B0210 Skin Infection – Tape-stripping: The skin tape stripping model measures the efficacy of a test article in a setting of superficial skin

infection where damage of underlying layers of the skin is undesirable or irrelevant for the desired

indication. In this model, superficial damage is achieved by successive application of an adhesive

bandage to strip off the fur and epidermis. After stripping, bacteria are allowed to adhere to the wound

for 4 hours prior to initiation of treatment. All mice are observed at least twice daily for mortality and

surviving mice are weighed and scored for wound severity. At the end of the experiment, the wound

area is excised, homogenized, and bacterial burden is determined by serial dilution.

Reportable Results: Wound Severity, CFU/g tissue, Log10 CFU reduction from control group

B0211 Surgical Site Infection—Suture: The suture model measures efficacy of a test article in the setting of a surgical sight infection. A surgical

suture is contaminated with the bacterium of interest prior to implantation into an incision wound on

the back of mice. The wound is closed with a single, non-contaminated suture and test or control articles

treatment is initiated 2 hours post-surgery. Mice are euthanized at 24 hours post-treatment and the

wound area is excised, homogenized and plated to determine the bacterial burden.

Reportable Results: CFU/g tissue, Log10 CFU reduction from control group

B0212 Wound Infection—Punch Biopsy: The punch biopsy wound model measures the efficacy of a test article in the setting of a full-thickness

skin wound. A large skin biopsy punch is used to great a 6.0 mm wound on the back directly above the

thoracic spinal column and adjacent musculature. Bacteria are allowed to absorb to the wound prior to

covering with adherent dressing. Treatment is initiated 4 hours after wounding. Mice are euthanized

after 7 days, the wound is excised, homogenized and plated to determine the bacterial burden.

Reportable Results: CFU/g tissue, Log10 CFU reduction from control group



B0213 Transcervical Chlamydia Persistence: In order to meet the needs of Chlamydia vaccine developers, Southern Research developed a C57BL/6

model of infection/colonization by human Chlamydia trachomatis isolates. Infectious elementary bodies

are delivered directly to the upper reproductive tract using a non-surgical technique that results in

infection/colonization for several days. The assay has been used successfully with serovars D and L2.

Reportable Results: Bacterial burden in the upper genital tract (by qPCR)

B0214 Pharmacodynamic Dose Fractionation: PK-PD based non-clinical data helps de-risk drug development and strengthens NDA submissions

because it is critical to setting a successful dosing regimen. A dose fractionation strategy, whereby the

same total accumulative dose is given across different numbers of administrations, is used to identify

both the PK-PD index associated with efficacy and the index magnitude required for efficacy.

Reportable Results: PK-PD indices versus Log10 CFU bacteria at the site of infection.

B0215 in vivo Resistance Monitoring: Often performed in conjunction with B0214 Pharmacodynamic dose fractionation, this assay measures

the frequency of resistant mutant generation following different dosing regimens. Bacteria are

harvested from target organs at specific time points and plated on media containing the test article.

Reportable Results: Frequency of resistance emergence

B0216 in vivo Post-Antibiotic Effect (PAE): PK-PD based non-clinical data helps de-risk drug development and strengthens NDA submissions

because it is critical to setting a successful dosing regimen. The post antibiotic effect (PAE) is defined as

persistent suppression of bacterial growth following exposure. Analysis of the in vivo PAE helps inform

dosing strategy and, in general, antibiotics that induce a stronger PAE are more desirable because they

would require less frequent administration. This analysis is typically performed using the neutropenic

mouse thigh assay. The in vivo PAE is calculated using the formula PAE = T – C – M where M is the time

serum levels exceed the MIC, T is the time required for CFU in the thighs of treated mice to increase by 1

Log10 above the count at time M, and C is the time required for CFU in the thighs of untreated mice to

increase by 1 Log10.

Reportable Results: PAE (hours)



B0217 Vaccine Immunogenicity Evaluation: Proof-of-concept immunogenicity studies are critical to moving a candidate vaccine from early

development into the clinic. Data from these experiments is used to establish the immunological

characteristics of the product and may guide selection of doses, schedules and routes of administration

for subsequent efficacy studies in nonclinical models and in clinical trials. Southern Research can support

immunogenicity testing in a number of nonclinical species including rodents and non-human primates.

In most cases, both antigen binding and functional activity (e.g., neutralization or opsonophagocytic

activity) can be measured.

Reportable Results: Total and functional antibody titer over time.

IND-Enabling Toxicology: For nearly 50 years, Southern Research has conducted nonclinical safety assessments for a wide variety

of chemical entities—from small molecule pharmaceuticals to biologics to vaccines. Today, we continue

to focus on the unique needs of each client in order to execute the most appropriately designed studies

for each situation, thus ensuring that the path to regulatory approval is as smooth as possible. Our

toxicologists are backed by highly trained technical staff and an array of in-house core services including

on-site bioanalytical, histopathology and clinical pathology support as well as robust, state-of-the-art

systems for data capture and management. Study types include acute and repeat dose (subchronic and

chronic) toxicity, carcinogenicity/oncogenicity, developmental and reproductive toxicology (DART),

neurotoxicity and neurobehavioral assessment.

Southern Research | Clinical Trial Support Services


Clinical Trial Endpoint Analysis

B0301 Opsonophagocytic Killing Assay (OPKA): Typically used as a non-clinical and clinical endpoint for the development of antibacterial vaccines or

therapeutic antibodies, the opsonophagocytic killing assay (OPKA) measures the titer of opsonic

antibody activity in sera. Briefly, the target bacterium is mixed with polymorphonuclear leukocytes

(PMNs) or differentiated HL-60 cells and the test sera. Relative killing is calculated as the percent

difference between viable CFU after 0 and 60 minutes of exposure.

Reportable Results: Percent relative killing.

B0302 Opsonophagocytic Uptake Assay (OPUA): The opsonophagocytic uptake assay (OPUA) measures the titer of opsonic antibody activity in sera.

Briefly, a fluorescently-labeled target bacterium is mixed with polymorphonuclear leukocytes (PMNs) or

differentiated HL-60 cells and the test sera. Uptake is calculated using flow cytometry.

Reportable Results: Percent uptake.

B0303 Serum Bactericidal Activity (SBA): The serum bactericidal assay (SBA) measures the ability of antibodies present in serum to mediate

complement-dependent pathogen killing. Log phase bacteria are mixed with serial dilutions of test sera

and an external source of complement. Following incubation, cells are washed and bacterial ATP

generation is measured in a microtiter format using a luciferase reporter. Bactericidal serum titers are

calculated as the reciprocal serum dilution necessary to obtain a 50% reduction in luminosity compared

to control wells.

Reportable Results: Bactericidal serum titer.

Additional Bioanalytical and Immunological Endpoint Assays: Southern Research is a highly collaborative, full-service Contract Research Organization. For nearly 50

years, we have stayed at the forefront of biomedical research and drug development. This perspective

allows our scientists to apply their vast experiences and deep expertise in service of your specific needs.

We can develop fit-for-purpose bioanalytical and immunological assays from early discovery phase to

clinical trials including Anti-drug Antibody (ADA) Assays, Neutralizing Antibody (Nab) quantification, and

Serum Drug Concentration.

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Achromobacter xyloxidans x x Bacillus cereusAcinetobacter baumannii x x x x x x xAggregatibacter sp. xAtopobium vaginae xBurkholderia cepacia complex x x x xBurkholderia multivorans xCampylobacter jejuni xCardiobacterium hominis xChlamydia trachomatis xClostridium difficile x x xEikenella corrodens xEnteric Group 137 xEnterobacter aerogenes xEnterobacter cloacae x x x xEnterococcus faecium x xEscherichia coli x x x x x xGardnerella vaginalis xHaemophilus influenzae x x xHaemophilus sp. xHelicobacter pylori xKingella sp. xKlebsiella pneumoniae x x x x x xListeria monocytogenes xMobiluncus curtisii xMobiluncus mulieris xMycobacterium abscessus x

Mycoplasma genitalium xNeisseria gonorrhoeae x x x

Neisseria meningitidis x

Proteus mirabilis x xPseudomonas aeruginosa x x x x x x xSalmonella enterica xShigella dysenteriae xStaphylococcus aureus x x x x x x x x xStaphylococcus epidermidis x xStenotrophomonas maltophilia x x xStreptococcus agalactiae xStreptococcus gordonii xStreptococcus oralis xStreptococcus pneumonia x x x xStreptococcus pyogenes xViridians streptococci xYersinia enterocolitica x

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Achromobacter xyloxidans x x Bacillus cereusChlamydophila pneumoniaeCitrobacter freundii xCitrobacter koseriClostridium perfringensEnterococcus avium xEnterococcus faecalis xKlebsiella oxytoca xLactobacillus acidophilusLegionella pneumoniaeListeria monocytogenesMoraxella catarrhalisMorganella morganiiMycobacterium aviumMycobacterium intracellularaeMycobacterium smegmatisMycobacterium tuberculosis x xMycobacterium ulceransMycoplasma pneumoniaePropionibacterium acnesProteus vulgaris xProvidencia stuartiiSalmonella enterica xSerratia marcescens xShewanella putrefaciens xVibrio cholera


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Documents

Antibiotic and Antibacterial Vaccine Development Services · B0105 Post-antibiotic Effect (PAE): The post-antibiotic effect (PAE) is an important pharmacodynamics (PD) parameter that