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By: Mary N. Wessling, Ph.D. ELS

In this blog we will unravel the terminology describing bacterial toxins. In general, there are at least three ways that bacterial toxins are described in the literature:

Below are examples of each:

Biological designation

When described by their biological designation a part of the genus or species name is used for the toxin. For example: Clostridium tetani produces Tetanus toxin and Corynebacterium diphtheriae produces Diphtheria toxin.

Origin of the toxin

Exotoxins (e.g. polypeptides) are toxins released by a cell, whereas endotoxins (e.g. lipopolysaccharides) are an integral part of the bacterial cell wall.

Body part damaged by the toxin

Bacteria may cause disease through their toxins that enter the body via the respiratory tract, gastrointestinal tract, genital tract, and the skin. Enterotoxins mostly affect the gastrointestinal tract. “Entero” comes from the Greek word “enteron” meaning intestine.

Bacterial enterotoxins include examples of exotoxins produced by some strains of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli).Staphylococcal enterotoxin acts on intestinal neurons to induce vomiting; E. coli producing Shiga toxin causes serious dysentery and can lead to hemorrhagic diarrhea and kidney failure.

You will also see other terms used to designate toxins…

Superantigens: toxins that cause over-reaction

Antigens are characterized by their ability to activate T-cells and other immune system cells; while the T-cell response is a normal part of the immune process, over-activation of T-cells can cause an inflammatory response that can result in shock and multiple organ failure.

Pore-forming toxins that open host cell membranes

Pore-forming toxins (PFT) are toxin proteins with the ability to spontaneously self-assemble forming transmembrane pores in the membrane of target cells. Staphylococcal alpha toxin, also known as alpha-haemolysin, makes specific pores in target cells which are part of the pathology of infection and a valuable tool in construction of nanopores. Tetanolysin is another pore forming toxin produced by C. tetani which can make cells permeable to materials for experimentation.

Intracellular toxins

These toxins have two-part structures and are termed AB toxins. The A stands for “active”, the B for “binding”, for the ways that the two structures cooperatively cause cell damage. In most cases, the B structural element attaches to the cell membrane and provides an entry point for the other part, the A-enzyme component that causes damage to the inside of the cell through its enzymatic activity.

Some AB toxins have more than one B moiety: for example, the cholera toxin has five B proteins that provide entry for the A moiety, so it is designated AB5. The A moiety is initially a coiled chain but once inside the cell it uncoils, where its enzymatic activity kills the enteric cell.

Ligand-receptor interactions

The actions of exotoxins and endotoxins depend on a process whereby a part of their molecular structure, a ligand, can bind or otherwise interact with a structure on the host cell being attacked, a receptor. Thus, this ligand–receptor interaction is crucial to most diseases produced by bacterial toxins.

Lethal dose 50%

Bacteria cause disease by toxin production, invasion and inflammation. All toxins damage or disrupt the functions of the host cells. The term that describes the level of danger presented to the host by a toxin is “Lethal Dose 50%”, abbreviated LD50; the lower the LD50, the lower the amount of toxin to cause death.

 

By: Rachel Berlin, Marketing Manager

Microbiome Research ReagentsMicrobiome research is uncovering the enormous potential for developing drugs, such a live biotherapeutic products, from the microbiome.  This burgeoning field is the future of medicine.

List Labs is excited and proud to support microbiome research by providing reagents to scientists studying the human microbiome. Below is a list of microbiome research studies that have used List Labs’ research reagents such as Athrax, Pertussis, Cholera and Difficile Toxins.

Pertussis Toxins Used in Microbiome Research:

Difficile Toxins Used in Microbiome Research: 

Cholera Toxins Used in Microbiome Research: 

Anthrax Products

 

In addition to producing products for microbiome research, List Labs also provides contract GMP manufacturing of live biotherapeutic products for phases 1-3 of clinical trials. For more information on microbiome and live biotherapeutics- check out this blog post or watch our informative video. See how scientists have used our products in their research on our citations page.

Contact us to discuss your next project!

Botulinum Toxin Protein

3D Rendering of Botulinum Toxin Protein

By: T.J. Smith

Following a botulism outbreak due to contaminated ham that severely sickened 10 and resulted in the death of three people in Ellezelles, Belgium, a review and case study on botulism was published by a researcher named Emile Van Ermengem (Van Ermengem 1897).  While Van Ermengem was not the first to study this syndrome, his article supplied critical information defining botulism as a type of food poisoning having specific paralytic symptoms.   He determined that the illness was an intoxication, not an infection, and that its cause was a bacterial toxin.  He was also able to isolate and characterize the organism responsible for the toxin as an anaerobic spore-forming bacillus, which he named Bacillus botulinus (later renamed Clostridium botulinum).  “Botulinus” is the latin word for sausages, and this nomenclature was used due to the historic link between botulism and improperly processed sausages, particularly blood sausages.  His careful and painstaking research provided the foundation for future studies on botulism, its causes and treatments.

During this time, botulism was thought to be related specifically to improperly processed meat, such as sausages and ham, and caused by a single monospecific toxin.  Within the next decade both of these theories were proven wrong.  In 1904, Dr. G. Landmann isolated a botulinum toxin-producing bacterial strain from preserved bean salad which had caused 11 deaths in Darmstadt, Germany (Landmann 1904).  This was the first reporting of botulism due to a source other than meat or fish.  In 1910, Leuchs showed that the Ellezelles strain from Van Ermengem and the Darmstadt strain from Landmann were immunologically distinct toxins, providing the first evidence that all botulinum neurotoxins were not the same (Leuchs 1910).  This marked the beginning of a century of study related to botulinum neurotoxin diversity which included clinical case reviews and morphological, immunological, and, most recently, genetic studies.

As the bacteria responsible for botulinum neurotoxins initially seemed to be nearly identical in morphology and cultural characteristics, early delineations were the result of serological studies, which were apparently the “hot new thing” of the day.  Antisera produced using a particular bacterial strain was tested against other strains to determine relationships among both the toxins and the bacteria that produced them.  The assays were both qualitative and quantitative and included agglutination, immuno-absorption, and neutralization techniques (Schoenholz and Meyer 1925).  They were originally targeted to both the toxins and the bacteria that produced them, but the emphasis quickly shifted to neutralization of toxins using specific antisera.  These antisera, which were predominantly of equine origin, were developed for treatment purposes as well, and they continue to be the only approved treatment for botulism to this day.  In 1919, Georgina Burke produced antisera from three strains isolated in California, Oregon, and New York, and she was able to show that the toxins from the two West Coast strains were immunologically identical, while the New York toxin was distinct (Burke 1919).  She identified these toxins as type A (West) and Type B (East).  Later studies of U. S. strains by K. F. Meyer and B. Dubovsky substantiated her findings (Meyer and Dubovsky 1922).

In the following decades several additional serotypes were identified.  In 1922, Dr. Ida Bengtson reported a toxin from a C. botulinum strain that was not neutralized by either type A or type B antisera, which she designated type C (Bengtson 1922).  The bacterial strain was isolated from fly larvae that proved to be causative agents in the intoxication of chickens that had ingested these larvae.  This illustrates that botulism is not restricted to humans but rather can be seen in a wide variety of animals as well.  In fact, differential sensitivities of the toxins in animals has formed a background for discerning various toxin types.  In addition, catastrophic losses due to botulism have been noted in domestic fowl, cattle, horses, and even minks and foxes, prompting the development and use of vaccines in these animals for protection.   H. R. Seddon isolated a culture that apparently produced type C toxin from an outbreak in cattle in Australia (Seddon 1922).  The toxin could be neutralized by Bengtson’s antisera, however, the reverse was not true.  This “one-way” neutralization was the first of several anomalies that were discovered when serotyping botulinum neurotoxins.

In 1929, Meyer and Gunnison showed that the toxin from a culture isolated by Theiler and associates in South Africa was immunologically distinct from types A, B, or C.  This toxin, which was also related to intoxication in cattle, was designated type D (Meyer and Gunnison 1929).

In the following decade, several botulism cases were noted that were related to ingestion of fish.  While Russian scientists were the first to note these unusual cases of botulism, it was Dr. Janet Gunnison who determined the toxins were a new type, and Dr. Elizabeth Hazen who published initial reports on type E botulism cases (Gunnison, Cummings et al. 1936, Hazen 1937).  Outbreaks due to dried, smoked, or fermented fish, fish eggs, whale blubber, and seal or walrus meat are common, but there have been rare type E cases related to other foods as well.

The first case due to type F was linked to an outbreak involving duck paste on Langeland Island, Denmark, in 1958 (Moller and Scheibel 1960).  Reported cases due to type F are rare and have been restricted to humans so far.  Type G was isolated from a cornfield in Argentina in 1969 as part of a soil sampling study conducted by Dr D. F. Gimenez and Dr. A. S. Ciccarelli (Gimenez and Ciccarelli 1970).  This type is unusual in that there are no direct reports of intoxications due to type G in people or animals.  However, a study of autopsy materials related to sudden deaths due to unknown causes in Switzerland identified type G producing organisms among the samples (Sonnabend, Sonnabend et al. 1981).  Why type G is only found in Argentina or Switzerland is a mystery.

As of 1970, there were seven known immunologically distinct botulinum toxin types.   However, as we will discover, this was just the beginning of our understanding of the diversity that is seen within botulinum neurotoxins.

About List Labs

List Labs offers over 100 reagents including Botulinum Toxins. These products are used in a wide variety of scientific research studies. You can read about some of them on our citation page. Contact us today to discuss your next project.

About the Author

Theresa Smith has studied botulinum neurotoxins for over 25 years, specializing in toxin countermeasure research, and is considered a leading expert regarding diversity in botulinum neurotoxins as well as the organisms that produce these toxins.

References

Bengtson, I. (1922). “Preliminary note on a toxin-producing anaerobe isolated from the larvae of Lucilia caesar.” Pub Health Repts 37: 164-170.

Burke, G. S. (1919). “Notes on Bacillus botulinus.” J Bact 4: 555-571.

Gimenez, D. F. and A. S. Ciccarelli (1970). “Another type of Clostridium botulinum.” Zentralbl Bakteriol Parasitenk Infektionskr Hyg Abt 215: 221-224.

Gunnison, J. B., et al. (1936). “Clostridium botulinum type E.” Proc Soc Exp Biol Med 35: 278-280.

Hazen, E. L. (1937). “A strain of B. botulinus not classified as type A, B, or C.” J Infect Dis 60: 260-264.

Landmann, G. (1904). “Uber die ursache der Darmstadter bohnenvergiftung.” Hyg Rundschau 10: 449-452.

Leuchs, J. (1910). “Beitraege zur kenntnis des toxins und antitoxins des Bacillus botulinus.” Z Hyg Infekt 76: 55-84.

Meyer, K. F. and B. Dubovsky (1922). “The distribution of the spores of B. botulinus in the United States. IV.” J Infect Dis 31: 559-594.

Meyer, K. F. and J. B. Gunnison (1929). “South African cultures of Clostridium botulinum and parabotulinum. XXXVII with a description of Cl. botulinum type D, N. SP.” J Infect Dis 45: 106-118.

Moller, V. and I. Scheibel (1960). “Preliminary report of an apparently new type of Cl. botulinum ” Acta Path Microbiol Scand 48: 80.

Schoenholz, P. and K. F. Meyer (1925). “The serologic classification of B. botulinus.” J Immunol 10: 1-53.

Seddon, H. R. (1922). “Bulbar paralysis in cattle due to the action of a toxicogenic bacillus, with a discussion on the relationship of the condition to forage poisoning (botulism).” J Comp Path Ther 35: 147-190.

Sonnabend, O., et al. (1981). “Isolation of Clostridium botulinum type G and identification of type G botulinal toxin in humans: report of five sudden unexpected deaths.” J Infect Dis 143: 22-27.

Van Ermengem, E. (1897). “A new anaerobic bacillus and its relation to botulism (originally published as “Ueber einen neuen anaeroben Bacillus und seine beziehungen zum botulismus” in Zeitschrift fur Hygiene und Infektionskrankheiten, 26:1-56) ” Clin Infect Dis 4: 701-719.

 

 

By: Mary N. Wessling, Ph.D. ELS

Bacterial Toxins used for Vaccine Research

List Biological Laboratories’ (List Labs) catalog of products is related to furthering research in human health and preventing disease, most commonly as the starting materials for vaccine research & development or production around the world. Vaccines are mainly identified for their capacity to prevent diseases that the body’s innate defensive mechanisms (the skin and specialized cells in the blood, for example) can’t resist unaided. However, there are many other uses for these purified materials in medical research, and you will likely encounter wording on our website that is not part of everyday vocabulary for non-scientists. This article is intended to provide a basic understanding of some of the more frequently used terms and aid you in selecting the products most essential to your projects.

Toxin vs. Toxoid

For starters, what is the difference between “toxin” and “toxoid”. Broadly defined, anything that can cause harm to an organism is a toxin. However, for List Labs’ products and in biological usage, a toxin refers to a bacterial or viral product that has harmful effects when it enters the body (List Labs’ toxins are in a highly purified form). A toxoid is a chemically altered toxin that has reduced or no toxicity and is used for its remaining antigenic activity, which can stimulate an immune response.

Take, for example, cholera, a disease produced by Vibrio cholerae bacteria, possibly through contact with body fluids from a person ill with cholera or through contaminated water supply. Cholera causes severe diarrhea, and untreated, it can be fatal. However, the purified List Labs’ cholera toxin by chemical modification becomes a toxoid that lacks toxic activity but retains structures that make it useful for immunization of research animals or stimulation of immune cells in vitro.

How do Toxoids Impact the Immune Process? 

To understand how some List Labs products work, an overview of the immune process is helpful. During the course of a day, we frequently touch, ingest, or breathe in something that has potential to harm the body. Our cells react to this invader: is this a threat, or not, and if so, how serious is the threat?

What is the Innate Immune Response? 

The innate immune response is the first order of defense in the immune process. There are many different cell types in our body. Some of these cells are equipped by their structural and biochemical components to destroy dangerous microbial invaders–pathogens–quickly. The inflammation that we experience from minor infections is often a sign of this process as cells from the blood destroy the pathogen. This happens quickly, within hours.

What is the Adaptive Immune Response?

Another cellular response system requires a longer time to react to the threat. These cells react by changing from an inactive form to one that will start a more complex defensive process: this is the second step, the adaptive immune response. There are two different classes of cells that comprise the adaptive immune response; they differ by the structures that give them their ability to bind antigens– the invading bacteria and viruses. Both these cells are called lymphocytes; individually, they are the B-lymphocytes (B-cells) and T-lymphocytes (T-cells). Both originate from stem cells in the bone marrow; B and T refer to the place in the body where they mature. T-cells mature in the thymus into several subclasses of T-cells that circulate in the blood and lymph. “Killer” T-cells recognize foreign antigens on cell surfaces (e.g. from viral infection or malignancy). “Helper” T-cells induce B-cells to produce antibodies. “Suppressor” T-cells dampen or regulate the immune response to prevent over-reaction. B-cells mature in the bone marrow and migrate to secondary lymphoid tissues (e.g. spleen and lymph nodes). When they encounter foreign antigens and/or helper T-cells, they are stimulated to divide and expand clonally to produce antibodies and differentiate into plasma cells.

What is Immune Memory? 

After the B and T-lymphocytes react to an antigen, two results are possible. The first, and desirable result, is that the invader is identified and defeated, leaving behind what might be called its criminal record: immune memory. When the antigen comes creeping back in the future, the adaptive immune system recognizes it and attacks. The second possibility is an over-reaction and lack of cessation of the adaptive immune process that is harmful to the body: an autoimmune condition.

Antigens, Epitopes and Vaccines

Where do vaccines come into this process? An antigen is a substance that causes the body to mount an immune response against it. Antigens include toxins, bacteria, viruses, or other substances that the body recognizes as foreign or not “self”. Vaccines have structural features similar to structures of the toxin or invading pathogen that can elicit adaptive immunity.

An epitope is a specific molecular region on the surface of an antigen, typically one of many on the antigen, that elicits an immune response and is capable of binding with the specific antibody produced by the response. A toxin has many epitopes that can be recognized by the immune response. The epitopes that are required for toxicity have been altered chemically in toxoids or by specific genetic mutations in inactive mutants; however, many epitopes are retained and can stimulate an adaptive or memory immune response that will be effective against the toxin.

Toxins and Toxoid Products for Research

Below is a list of toxin and toxoid or inactive mutant pairs of products available to support your research.

Toxin and product numbers Toxoid Inactive Mutant
Botulinum Neurotoxin Type A from Clostridium botulinum – 130A, 130B, 9130A 133L
Botulinum Neurotoxin Type B, Nicked, from Clostridium botulinum – 136A, 136B 139
Toxin A from Clostridium difficile – 152C 153
Toxin B from Clostridium difficile – 155A, 155B, 155L 154A
Diphtheria Toxin, Unnicked, from Corynebacterium diphtheriae – 150 151 149
Enterotoxin Type B from Staphylococcus aureus – 122 123
Tetanus Toxin from Clostridium tetani – 190A, 190B 191A, 191B

 

 

List Labs Contract GMP ManufacturingBy: Rachel Berlin, Marketing Manager

List Labs provides expert GMP contract manufacturing services to aid you in developing product for your clinical trial. The List Labs difference is that we manufacture reagent grade biological toxins regularly for resale, which means that not only do we have current, state-of-the art facilities and equipment, but we also have the experience and expertise to provide our customers with the highest quality products available. We even have a GMP LPS product currently in stock. Here are five reasons List Labs can make a critical difference in your success as a GMP manufacturing partner.

  1. Product Manufacturing Experience

List Labs has nearly 40 years of experience cultivating anaerobic and aerobic organisms. Because we manufacture our own products, we are up to date with the most current regulations and best practices for the highest quality of product manufacturing. We are used to cultivating hard to grow organisms and thrive on the challenge.

  1. Biological Toxins Expertise

Our team of scientists, many with PHDs, have the expertise for manufacturing obligate anaerobes, spore forming organisms as well as aerobes. The majority of List Labs’ scientific management team has been here for over 20 years and has vast experience manufacturing biological toxins for research. As experts in their field, our scientists utilize their expertise to produce the highest quality research reagents on the market.

  1. Quality Research Reagents

List Labs produces only the highest quality products for our customers to conduct their research. We are known for our quality products and attention to detail throughout the industry. Over the past 40 years in business, List Labs has honed our processes and facilities to produce only the highest quality research reagents and GMP compliant products.

  1. Facilities Designed for GMP

Our state-of-the-art facility was designed with GMP work in mind and is constantly enhanced with new equipment and more efficient processes. Our lab provides containment for BL2 and BL3 organisms and spores, as well as segregation of projects. Contact us to come visit us and tour our facility.

  1. GMP Capabilities

List Labs’ contract research & manufacturing capabilities include analytics, process development, media optimization, downstream and upstream processing and bulk and final product lyophilization. Most of our cultivation and harvesting operations are in full closed systems. We are also capable of working with spore formers, which many organizations are unable to work with due to the difficult nature of these strains and regulatory compliance. List Labs is one of only about 16 private companies in the US registered with the Federal Select Agent Program.

When choosing your GMP partner – make sure it’s someone you can trust. Consider List Labs for your next GMP project.

Contact us today! 

List Labs' founder Linda Shoer

List Labs’ founder Linda Shoer

The origin of businesses is often an interesting story. List Biological Laboratories is no exception. The company was founded in 1978 by Linda Shoer. Linda was an entrepreneurial scientist in Silicon Valley, who’d been relocated with her husband from Boston. She had an idea for a company and leveraged an initial order into a loan from a bank, fearless that her vision would be successful. That order and loan served as the starting point for List Laboratories. The first product was a Cholera Toxin.

List Labs Develops Full Range of Bacterial Toxins and Contract Manufacturing Services

Linda had a clear plan for the company and it involved the development of a product line devoted exclusively to Bacterial Toxins and related products. List Labs was the first to commercialize many bacterial toxins for research including C. difficile Toxins and Pertussis Toxins.

Linda was well connected and comfortable networking with colleagues and proposing new business ideas or ventures.  She got the company involved in contract manufacturing and consulting early on. In the 90’s List Labs was instrumental in the manufacturing of a very popular injectable consumer product to smooth facial wrinkles.   Upon her death, she left the business to the current management team; a team that has now worked together for over 20 years.

List Labs – Still Women-Owned and Cutting Edge

Shoer’s presence is still strongly felt and the company has always remained a women owned and operated business. In an era of takeovers and transition, List Laboratories has remained true to its founding and focus. Today, the List Labs catalog offers over 100 products including Toxins, Peptides, Antibodies and Lipopolysaccharides. Many of the employees have worked together for decades.

In 2008, the company built out a new lab, complete with state of the art equipment.   List has produced several batches of high purity proteins used to test vaccines. Additionally, the company specializes in the production, shipment and handling of dangerous goods. In the last several years List Labs has worked on a variety of microbiome projects, custom fills, development work and special Select Agent projects on various subtypes of Botulinum Toxin. We have also provided GMP product for many phase 1 and 2 clinical trials. We enjoy the variety of work and welcome inquiries from new customers.  

Today, List Labs takes great pride in its reputation for high quality products and exceptional customer service. The company works with businesses and organizations worldwide on custom projects or contract manufacturing opportunities as well as selling a broad array of toxins and related products. List Labs heart is in the science and the discovery of innovative solutions. Their office is located in Campbell, CA, in the Silicon Valley. If you have questions about any of our products or services, contact us today!

By: Md. Elias, Ph.D, Senior Scientist

List Labs is one of the leading manufacturers of high quality adjuvants from bacterial sources. Our highly purified adjuvants for research and development are Tetanus Toxoid (Product #191), Cholera Toxin B Subunit (Product #104), Diphtheria Toxin CRM197 Mutant (Product #149), Adenylate Cyclase Mutant, Cya-AC– (Product #198L), Pertusis Toxin Mutant (Product #184), and LPS and its derivatives (Products #400, #401, #421, #423, #433, #434). GMP grade material is available by custom order.

In immunology, an adjuvant is a component that enhances and/or potentiates the immune responses (humoral and /or cell mediated) to an antigen and modulates it to achieve the desired immune responses. Adjuvants can be used for various reasons: (i) to enhance the immunogenicity of antigens; (ii) to reduce the amount of antigen or the number of immunizations needed for protective immunity; (iii) to improve the efficacy of vaccines in immune-compromised persons; (iv) to increase functional antibody titer; or (v) as antigen delivery systems for the uptake of antigens by the mucosa (1-3). Brief descriptions of List Labs products that have potential uses as vaccine adjuvants or immune modulators are provided below. For more details, please visit www.ListLabs.com.

Tetanus Toxoid (Product #191): Tetanus toxoid is prepared by formaldehyde inactivation of pure neurotoxin (Product #190). There are FDA approved vaccines that use a tetanus toxoid antigen to protect children and adult against tetanus such as DAPTACEL and Tripedia, and others that use it as a carrier in conjugate vaccines against various pathogens. For example, MenHibrix® is an FDA approved vaccine where tetanus toxoid has been conjugated to Neisseria meningitidis serogroup C and Y capsular polysaccharides and Hib capsular polysaccharide. Several other tetanus toxoid conjugated vaccines are in research and investigation stages such as Type III group B streptococcal polysaccharide-tetanus toxoid conjugate vaccine (4). Information on our entire family of Tetanus products can be found at https://listlabs.com/products/tetanus-toxins-&-related-products/.

Cholera Toxin B subunit (Products #103B and #104): Cholera toxin B subunit (CTB) is the cell binding domain of cholera toxin protein complex. The holotoxin consists of a single A subunit bearing ADP-ribosyl-transferase activity surrounded by five B subunits that bind to GM1 ganglioside receptors on mammalian cell surfaces and facilitate entrance of the A subunit into cells. The non-toxic CTB has been shown to be an efficient mucosal adjuvant and carrier molecule for the generation of mucosal antibody responses and/or induction of systemic T-cell tolerance to linked antigens. Due to the ubiquitous presence of the GM1 ganglioside receptor on eukaryotic cell membranes, CTB has been extensively used as a conjugate and non-conjugate vaccine adjuvant in a wide variety of model systems.

A CTB-urease conjugated vaccine has been shown to prevent infection by Helicobacter pylori, a bacterium that infects greater than 50% of world population and can cause a variety of gastrointestinal diseases (5). A series of studies have been carried out to develop CTB carrier based vaccines to prevent HIV-1 (6) and West Nile Virus infections (7). CTB has been used as a component of a skin patch for transcutaneous immunization against hepatitis B virus in a mouse model (8). Besides the adjuvant activity, recent studies show that CTB can suppress immunopathological reactions in allergy and autoimmune diseases such as Crohn’s disease (9). Information on our entire family of Cholera products can be found at https://listlabs.com/products/cholera-toxins/.

Diphtheria Toxin CRM197 Mutant (Product #149): CRM197 is a non-toxic mutant of diphtheria toxin lacking the ADP-ribosylation activity (10). CRM197 results from a naturally occuringsingle base change (glutamic acid to glycine) in the toxin gene which is immunologically indistinguishable from the native diphtheria toxin. CRM197 functions as a carrier for polysaccharides and haptens making them immunogenic (11, 12). It is utilized as a carrier to develop conjugate vaccines for diseases such as pneumococcal and meningococcal infections. MenACWY-CRM is an approved vaccine to protect adults and adolescents against disease caused by meningococcal serogroups A, C, W-135 and Y. Information on our entire family of Diphtheria products can be found at https://listlabs.com/products/diphtheria-toxins/.

Adenylate Cyclase Toxoid, Cya-AC– (Product #198L): A genetically modified adenylate cyclase toxin (ACT) lacking adenylate cyclase activity (CyaA-AC–) has been produced (13). Although the catalytic activity is destroyed, CyaA-AC– is still cell invasive and able to induce an immune response to co-administered pertussis antigens (14, 15).  CyaA-AC– has been shown to promote delivering of vaccine antigens into the cytosol of major histocompatibility complex (MHC) class I antigen-presenting cells (16). CyaA-AC– has been used as a tool to deliver antigens to T-cells in anti-cancer immunotherapeutic vaccines (17, 18).

Pertussis Toxin Mutant (Product #184): List Labs produces Pertussis Toxin Mutant, a genetically inactivated form of pertussis toxin where mutations were introduced to abolish the catalytic activity of the S1 subunit while the toxin complex still retains the cell binding ability (19). A pertusis toxin mutant has been used as an adjuvant or as a carrier to promote an immune response. These studies indicated that pertussis toxin mutant possesses adjuvant properties with the ability to encourage both local and systemic responses, to promote T helper cell responses to co-administered antigens and to favor the production of Th1/Th17 cells, important in mediating host immunity to infectious pathogens (20). Pertusis toxin binds to the cell receptor, TLR4 which activates Rac and subsequently causes various effects depending on the type of cell treated (21). The toxin or binding oligomer induces dendritic cell maturation in a TLR4-dependent manner (22). Information on our entire family of Pertussis products can be found at https://listlabs.com/products/pertussis-toxins-&-virulence-factors/.

LPS and its derivatives: List Labs provides LPS and various derivatives: highly purified HPTTM LPS from Escherichia coli O113 (Product #433); Ultar Pure Escherichia coli O111:B4 LPS (Product #421); Escherichia coli O55:B5 LPS (Product #423); Ultra pure LPS from Salmonella Minnesota R595 (Product #434); Lipid A Monophosphoryl from Salmonella Minnesota R595 (Product #401) and highly purified HPTTM LPS from Bordetella pertusis strain 165 (Product #400). For other LPS products please go to our product website. These LPS products are widely used as vaccine adjuvants and immune stimulators.

LPS is a potent stimulator of the vertebrate innate immune system mediated by macrophages and dendritic cells and generates a rapid response to infectious agents. Structural patterns common to diverse LPS molecules are recognized by Toll-like receptors (TLR) and accessory proteins in serum.  LPS released from bacterial membranes is bound to LPS binding protein (LBP) in serum, transferred to CD-14, an LPS receptor glycoprotein, and presented to the TLR-4-MD-2 complex, stimulating production of cytokines. LPS has a wide range of uses in research and drug development.  It may be used to stimulate immune cells and investigate the innate immune responses.  In drug development, structurally modified LPS forms, such as monophophoryl lipid A (MPLA) have been used as adjuvants in a wide range of vaccine formulations. MPLA, a TLR4 agonist has been formulated with liposomes, oil emulsions, or aluminium salts for several vaccines such as malaria vaccine (known as RTS,S) that is comprised of MPLA and a detoxified saponin derivative, QS-21 (3). Information on our entire family of Lipopolysaccharides can be found at https://listlabs.com/products/lipopolysaccharides/.

List Labs specializes in producing high quality adjuvants for vaccine development and is interested in partnering with others on new projects.  See some of our special projects or contact us for more information.

  1. Lee S.,Nguyen M.T. Recent advances of vaccine adjuvants for infectious diseases. Immune Netw. 2015, 15(2): 51-7. PMID: 25922593
  2. Petrovsky N., Aguilar J.C. Vaccine adjuvants: current state and future trends. Immunol Cell Biol.2004, 82(5): 488-96. PMID: 15479434 
  3. Alving C.R., Peachman K.K.,Rao M., Reed S.G. Adjuvants for human vaccines. Curr Opin Immunol. 2012, 24 (3):310-5. PMID: 22521140 
  4. Baker C.J., Rench M.A., McInnes P. Immunization of pregnant women with group B streptococcal type III capsular polysaccharide-tetanus toxoid conjugate vaccine. 2003. 21(24)3468-72. PMID: 12850362
  5. Guo L., Li X., Tang F., He Y., Xing Y., Deng X., Xi T. Immunological features and the ability of inhibitory effects on enzymatic activity of an epitope vaccine composed of cholera toxin B subunit and B cell epitope from Helicobacter pylori urease A subunit. Appl Microbiol Biotechnol. 2012, 93(5):1937-45. PMID: 22134639
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By:
Debra Booth, VP of Operations
Linda Eaton, Ph.D., VP of Research & Development
Stacy Burns-Guydish, Ph.D., Senior Director of Microbiology
PJ Nehil, Sales & Distribution Coordinator

Dear Researchers Everywhere,

List Labs recently exhibited at the 2016 BIO International Convention. As a producer of bacterial products for research, as well as a provider of custom laboratory services, we were excited to meet with current and potential customers. We were eager to gain some insight into the current and future state of biotechnology and the up and coming field of microbiome research. But you never know exactly how you’ll feel until you spend the time in the conference exhibit hall. We were very pleased to see that we are a part of an industry that is moving forward at the pace of a start up, fueled by the novel ideas and intellect of many scientists.

Last week, thousands of people filled the Moscone Convention Center in San Francisco. The event was brilliantly organized and the venue was strategically arranged. The various pavilions were organized by state or country and some by specialty. It was a great opportunity to network and identify new sources for projects and services. Attendees were CEO and business development folks interested in learning more about what exhibitors have to provide. At our booth, we talked about immunotherapy, live biotherapeutics, contract manufacturing, GMP production, and more. It was a pleasure to shake hands with many customers, distributors, and colleagues and discuss ways we can partner with them to move their research forward.

We also had the opportunity to meet with vendors, in shipping, supplies and services. These vendors are critical to delivery of our biological and therapeutic products, and we benefited from learning about their new offerings as strategic partners. The enthusiasm was palpable from both exhibitors and attendees. At this event, we didn’t just meet industry veterans. We met many young scientists and job seekers looking for their first break. Some even came directly to us to hand-deliver their resumes. The event had a job expo, fueling another layer of energy and opportunity for exhibitors. We were resident in the California Pavilion where we learned that the State of California has a Biosciences Training Program, which will help companies pay for new employment training. Community colleges around the country are encouraging students to contribute to the future of biotechnology through clinical and regulatory apprenticeships. It’s great to see that science is providing opportunity for students in so many ways.

In closing, we found the 2016 BIO International Convention to be highly productive for our company. For those of you who didn’t get a chance to meet us at the convention, it’s very easy to reach us online and on social media. We would love to connect with you on LinkedIn, tweet with you on Twitter, like each other on Facebook and Google+. You can also check these accounts if you’re curious about your next opportunity to meet us at a conference. We even have a YouTube channel and a blog where you can learn more about us. We’d love to see your YouTube videos and read your blog if you have them as well. The future of biotechnology looks bright and we’re more excited than ever to be a part of it. We will definitely attend more events like this and we hope to see you at BIO 2017 in San Diego!

Regards,
Debra, Linda, Stacy, & PJ

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