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Immunology

The lymphatic system 5: vaccinations and immunological memory – Nursing Times

Vaccines use components of infectious agents such as bacteria and viruses to stimulate the bodys immune system to recognise and mark them for destruction, preventing the infectious agents from replicating and causing infection. This article is the fifth in a six-part series about the lymphatic system

This article, the fifth in a six-part series on the lymphatic system, examines the role of antibodies in developing immunity to infectious viruses and bacteria. It also summarises the history of vaccine development and explains how different vaccines stimulate an immune response.

Citation: Knight J, Nigam Y (2021) The lymphatic system 5: vaccinations and immunological memory. Nursing Times [online]; 117: 2, 38-42.

Authors: John Knight is associate professor in biomedical science; Yamni Nigam is professor in biomedical science; both at the College of Human and Health Sciences, Swansea University.

Vaccination is very much in the news as the first vaccines to combat SARS-Cov-2, the coronavirus responsible for Covid-19, gain regulatory approval. This article, the fifth in a six-part series on the lymphatic system, examines in greater detail the nature of antibody-mediated immunity discussed in part 3 and explores how vaccines can be used to prime the immune system against infectious diseases.

As highlighted in part 3, which discussed the role of the lymphatic system in developing immunity, antibodies are produced by B-lymphocytes when the body is exposed to foreign material. Any foreign material that can elicit a specific immune response and stimulate the production of antibodies is referred to as an antigen (Aryal, 2018). This article focuses on those associated with pathogens that cause infectious diseases. When antibodies are generated during infection their major role is to bind to the infectious agent, marking it for destruction by the immune system; this process is termed opsonisation (see part 3).

Antibodies (also known as immunoglobulins) are soluble globular proteins. The most abundant antibody circulating in the blood is immunoglobulin G (IgG), which accounts for around 10-20% of the total plasma protein content (Vidarsson et al, 2014).

Antibodies have a characteristic molecular configuration, often described as resembling the letter Y. Each molecule consists of four polypeptide (protein) chains, linked by disulphide bonds (Fig 1). Each antibody molecule consists of two heavy chains and two light chains in a Y shape (Fig 1a); the stem region is constant but the terminal ends of the arms are highly variable. These variable portions are the antigen-binding sites and resemble three-dimensional clefts or pockets into which the corresponding antigen will fit.

Antibody molecules are highly specific: each is usually only able to bind to a single antigen (Fig 1b). Just as a key will only fit one particular lock, an antigen will only fit into its complementary antibody by slotting into one of its antigen-binding sites this is essential to the way antibodies recognise and bind to foreign material.

When antibodies are generated against a pathogen, most bind to that pathogen alone, although some can bind to molecules with similar configurations as their original target antigen (Jain and Salunke, 2019). Such cross-reactivity is known to be associated with many autoimmune diseases, such as rheumatic fever.

The process of clonal selection (Fig 2) is at the heart of antibody-mediated immunity. B-cells (B-lymphocytes), which generate antibodies, circulate in the blood and are also present in lymphoid organs, such as the spleen, bone marrow and lymph nodes. A typical human body has billions of B-cells, with many displaying antibody molecules with unique antigen-binding sites.

The red circle in Fig 2 represents a particle of foreign material such as a bacterium or virus. When pathogens enter the body they typically circulate in the blood and lymph and through the lymphoid organs, and randomly come into contact with B-cells. The antigens on the surface of the pathogen will fit into the antigen-binding site of a complementary antibody molecule just like a key slotting into a lock (Fig 2). Once this occurs, clonal selection is deemed to have taken place; the B-cell will divide repeatedly, producing a large population of clones of the original B-cell (Silverstein, 2002). The majority of newly generated B-cell clones mature and enlarge into antibody-producing plasma cells, which release antibodies (IgG) into the blood (Fig 2). These will circulate throughout the body and bind to and opsonise the pathogen when they encounter it, marking it for destruction.

Not all B-cells generated by clonal selection mature into antibody-producing plasma cells. A significant proportion remain in the body for many years as memory cells (Ratajczak et al, 2018). These display the same antibody as the original B-cell clone and effectively hold a long-term memory of the encounter (Fig 2). If the pathogen is encountered again, these memory cells ensure clonal selection can occur quickly, allowing rapid killing of the pathogen before it can cause disease.

There are many different forms of vaccination, but all work on the same basic principle of priming the immune system against a potential infectious pathogen. This involves introducing a harmless form of the pathogen (or a component derived from it) to initiate clonal selection, antibody production and production of a pool of circulating memory cells.

Just as a key will only fit one particular lock, an antigen will only fit into its complementary antibody

English physician Edward Jenners use of a cowpox inoculation to provide immunity against the deadly smallpox virus is recognised as a key foundation in the newly emerging field of immunology and led to the development of the first effective and widely used vaccine. Jenner noted that milkmaids frequently contracted the relatively mild viral infection cowpox, which appeared to protect them against smallpox. He began using cowpox inoculation in 1796 but it was not until 1840 that widespread vaccination against smallpox using the cowpox vaccine became available (Riedel, 2005). International use of smallpox vaccines led to its global eradication in 1980 and it remains the only infectious disease to be completely eradicated through the use of vaccination. Following Jenners success, research into vaccines boomed and has continued since with key vaccines developed against some of the most virulent and deadly human pathogens, including those causing typhoid (1896), diphtheria (1942), polio (1956), measles (1968) and rubella (1970).

These are the earliest vaccines successfully used to confer immunity. They use micro-organisms that display limited pathogenicity in humans to stimulate the production of antibody and memory cells against highly pathogenic bacteria and viruses; because this is how Jenners original smallpox vaccine using cowpox functioned, these types of vaccines are often referred to as Jennerian vaccines (Esparza et al, 2018). With more advanced vaccine techniques now available, there are few pure heterologous vaccines that are in general use today, although the Bacillus Calmette-Gurin (BCG) vaccine, which provides protection against tuberculosis (TB), is an example of an attenuated heterologous vaccine.

These vaccines use live micro-organisms that have been rendered less pathogenic (attenuated) either by culturing and selecting for less virulent strains or by manipulating the biological properties of the pathogen. Once administered, the constituent micro-organisms replicate freely within the body, generating a natural immune response but without causing the disease. A major advantage of these vaccines is that they elicit a powerful immune response that closely mirrors that seen in people exposed to the disease-causing pathogen. They tend to generate high antibody titres (concentrations) and a large pool of circulating memory cells, meaning booster shots are not usually required.

Attenuated live vaccines are not usually offered to people with a weakened immune system because, in the absence of a normal immune response, the component pathogens can replicate quickly, potentially leading to serious systemic infection. People who are likely to be immunosuppressed include those with congenital immune deficiencies, those undergoing chemotherapy or radiotherapy, transplant recipients and patients using corticosteroids to manage chronic inflammatory or autoimmune disease (Arvas, 2014).

One of the first attenuated vaccines developed was the BCG vaccine, which is used to vaccinate against Mycobacterium tuberculosis, the bacterium causing TB. BCG uses the closely related pathogen M bovis, which causes TB in cattle and is a zoonotic bacterium (capable of crossing species barriers and infecting a variety of animals). It can also infect humans, causing zoonotic TB, which has symptoms often indistinguishable from those caused by M tuberculosis (World Health Organization, 2017).

In 1908 French microbiologists Albert Calmette and Camille Gurin began culturing M bovis isolated from an infected cow. After 11 years and over 230 subcultures, they isolated a strain that failed to cause TB in a variety of experimental animals. This attenuated strain was named Bacillus Calmette-Gurin (BCG) and was first used to vaccinate humans against TB in 1921. Initially the vaccine was given orally, before intradermal administration into the skin became commonplace (Luca and Mihaescu, 2013).

Early vaccinations proved successful in conferring immunity against TB, and many countries adopted BCG vaccination. However, in 1930 a batch of BCG vaccine contaminated with virulent bacteria caused the deaths of 73 infants in the German city of Lbeck. The so-called Lbeck disaster was caused by negligent production of the vaccine. It undermined confidence in the vaccine worldwide (Fox et al, 2016) and is generally recognised as the first major incident to cast global doubt on the safety of vaccines. It was not until the 1940s and 1950s, when TB infections increased significantly, that the BCG vaccine was used again in vaccination programmes and proven to be safe.

Recent evaluations suggest that BCG is 70-80% effective in protecting against severe forms of TB, although it is less effective in adults than in children. Its widespread use has dramatically reduced the incidence of TB in many countries, although infections have started to rise again in many regions, along with antibiotic-resistant strains of M tuberculosis. Due to its relatively low incidence in the UK, the BCG vaccine is only given on the NHS to children and adults at increased risk of TB (NHS, 2019a).

BCG remains one of the worlds most widely used vaccines and is also used as an immunotherapy to upregulate the immune system in the treatment of bladder cancer (see part 6). Modified forms are also used to enhance immune responses in the treatment of a variety of bacterial, viral and parasitic diseases (Zheng et al, 2015) and it is currently being evaluated for use in treating Covid-19 (Curtis and Sparrow, 2020).

Other attenuated vaccines used in the UK vaccination schedule include MMR (measles, mumps and rubella), nasal flu, shingles, chickenpox and rotavirus vaccines (Vaccine Knowledge Project, 2019).

These vaccines incorporate whole pathogens that have been killed, usually by heating or by exposing them to noxious chemicals or ionising radiation, rendering them unable to infect, replicate and cause disease. The current polio vaccine is an inactivated whole-pathogen vaccine; and is initially given as a component of the 6-in-1 vaccine, which also affords protection against diphtheria, hepatitis B, Haemophilus influenzae type b (Hib), tetanus and pertussis (whooping cough). The 6-in-1 vaccine is given as three doses at eight, 12 and 16 weeks of age (NHS, 2019b). Subsequent boosters are required at the age of:

Because inactivated whole-pathogen vaccines cannot replicate, they tend to elicit much weaker and shorter-lived immune responses than live attenuated vaccines. Repeated doses are required to generate an adequate immune response, followed by booster vaccinations to maintain immunity.

To help enhance the immune response to inactivated vaccines, the killed pathogen is usually suspended in a fluid containing irritants such as aluminium salts, which act as an adjuvant. When injected, adjuvants initiate an inflammatory response, increasing blood flow to the site to strengthen and amplify the immune response.

The inflammation initiated by adjuvants can result in tenderness and pain at the injection site, which usually resolves after a few days (Vaccine Knowledge Project, 2019). Because inactivated whole-pathogen vaccines contain no viable pathogen, they can usually be given safely to immunocompromised patients (Arvas, 2014). Other examples of inactivated whole-pathogen vaccines include the annual winter influenza vaccine and the rabies vaccine (Vaccine Knowledge Project, 2019).

Unlike inactivated whole-pathogen vaccines, subunit vaccines contain no intact bacterial or viral particles but use fragments of material derived from the target micro-organism. The pathogen-derived subunits chosen are typically components of bacterial cell walls and viral envelopes, as these are the natural antigens that would trigger clonal selection and antibody production during infection.

Today most subunit vaccines are made using recombinant DNA techniques. A good example is the vaccine for the hepatitis B virus (HBV); here the gene for an antigen on the HBV surface is inserted into brewers yeast. This genetically modified yeast can be cultured and will synthesise the HBV surface antigen, which can be harvested and purified for use in the HBV vaccine (Das et al, 2019). Subunit vaccines are particularly useful for highly pathogenic micro-organisms, as the lack of any intact viable pathogen ensures infection is impossible, even in severely immunocompromised patients.

Many of the vaccines currently being developed against SARS-Cov-2 are subunit vaccines using the surface spike protein that allows the virus to enter its target cells. The vaccine developed at the University of Oxford designated ChAdOx1 nCoV-19, which is currently being rolled out, takes the gene for the SARS-Cov-2 spike protein and inserts it into a non-pathogenic chimpanzee adenovirus. Following vaccination, the genetically modified adenovirus will infect target cells, which then synthesise large quantities of the SARS-Cov-2 spike protein, triggering antibody production. If the vaccinated patient comes into contact with SARS-Cov-2, their immune system will be able to target the virus and prevent infection (Mahase, 2020a).

The symptoms associated with many bacterial infections are caused by toxins produced by the pathogen. For example, Corynebacterium diphtheria (responsible for diphtheria) generates a powerful toxin that inhibits protein synthesis in the body, damaging the respiratory tract, nerves and heart (Murtaza et al, 2016). The diphtheria vaccine uses a modified version of this toxin, which has been inactivated with a chemical (usually formalin). The modified toxin is referred to as a toxoid (toxin-like molecule); because it is structurally almost identical to the original diphtheria toxin, it elicits antibody production when used in a vaccine. If a vaccine recipient becomes infected with diphtheria, these antibodies bind to and neutralise the diphtheria toxin reducing or eliminating symptoms. Although the pathogen itself is not being targeted, eventually the persons immune system can target and eliminate the C diphtheria bacterium itself.

Some antigens on the surface of pathogens do not naturally elicit a strong immune response when used in vaccines. Conjugated vaccines can improve immune responses to these relatively weak antigens by linking (conjugating) them to other molecules, such as bacterial toxoids, which generate more robust immune reactions. The Hib vaccine is a good example of a conjugated vaccine. Hib is unrelated to viral influenza; it is a bacterial infection that typically infects babies and young children, causing potentially life-threating septicaemia and bacterial meningitis. The Hib vaccine takes portions of the bacterial cell wall and conjugates them to toxoids (commonly tetanus or diphtheria toxoids) to render them more powerful elicitors of antibody production (Heath and McVernon, 2002).

With recent advances in molecular biology allowing the rapid sequencing and manipulation of DNA, attention has turned to using this technology to design and produce a new generation of vaccines. DNA and RNA vaccines use the bodys own cells to make antigenic components of bacteria and viruses to trigger an immune response. For example, a DNA vaccine can be created by inserting the sequence of a viral protein into a small, ring-shaped piece of DNA called a plasmid, which is then injected into a muscle. The muscle cells take up the plasmid and use the information encoded in its sequences to make the viral protein; this stimulates the production of antibodies via normal clonal selection.

Although DNA vaccines are already licensed for veterinary use, none are yet licenced for use in humans. However, clinical trials are exploring their use against a variety of human pathogens, including the Ebola, Marburg and Zika viruses. Early results have been encouraging, with boostable antibody production reported (Liu, 2019).

The current coronavirus pandemic has advanced novel vaccine development: one of the first SARS-Cov-2 vaccines to undergo clinical trials was an RNA-based vaccine developed in the US. This uses messenger RNA (mRNA) sequences that code for the SARS-Cov-2 spike protein (Fig3); these are enveloped in a lipid coating and injected into the deltoid muscle. The mRNA will then initiate production of the spike protein in human cells, stimulating production of antibodies against the virus. Initial findings reported in July 2020 indicated the vaccine is effective in producing specific immune responses against SARS-Cov-2 without any trial-limiting safety concerns (Jackson et al, 2020). The vaccine, now known as the Moderna vaccine, was approved for use in the US in December 2020; earlier that month a similar RNA vaccine, developed by Pfizer and BioNTech, became the first SARS-Cov-2 vaccine to receive regulatory approval in the UK (Mahase, 2020b).

The anti-vaccination movement is as old as modern vaccination itself. When the effectiveness of Jenners smallpox vaccine became apparent, the Vaccination Act in 1840 made it mandatory for parents in the UK to vaccinate their children. This led to significant public opposition and the formation of the Anti-Vaccination League, which successfully campaigned for removal of penalties and for parents right to conscientiously object to vaccination (Hussain et al, 2018). Although the contaminated BCG vaccine that led to the Lbeck disaster shook public confidence in early TB vaccination programmes, the effectiveness of successive new vaccines against a variety of deadly diseases ensured that vaccine uptake was maintained at a high level.

The modern anti-vaccination movement was given great impetus by a paper published in The Lancet that linked the MMR vaccine with the development of autism in young children (Wakefield et al, 1998). Despite being widely criticised in the scientific community, and later retracted by The Lancet, there was widespread loss of public confidence in the vaccine. In the UK, uptake of the MMR vaccine dropped from 92% in 1996 to 84% in 2002 and in parts of London to as low as 61% which is far below the threshold required for herd immunity against measles. Unsurprisingly, cases increased significantly and in 2008 measles was declared endemic in the UK for the first time in 14 years (Hussain et al, 2018).

MMR vaccination has recovered in recent years and, currently, scheduled childhood vaccine uptake in the UK remains high. However, there is a major concern that increased use of the internet and social media to promote anti-vaccination messages will further undermine confidence in the safety of vaccines and reduce uptake (Gilroy, 2019).

Arvas A (2014) Vaccination in patients with immunosuppression. Turkish Archives of Pediatrics; 49: 3, 181-185.

Aryal S (2018) Antigen Properties, Types and Determinants of Antigenicity. Microbiologyinfo.com

Curtis N, Sparrow A (2020) Considering BCG vaccination to reduce the impact of COVID-19.The Lancet; 395: 1545-1546.

Das S et al (2019) Hepatitis B vaccine and immunoglobulin: key concepts. Journal of Clinical and Translational Hepatology; 7: 2, 165-171.

Esparza J et al (2018) Beyond the myths: novel findings for old paradigms in the history of the smallpox vaccine. PLoS Pathogens; 14: 7, e1007082.

Fox GJ et al (2016) Tuberculosis in newborns: the lessons of the Lbeck Disaster (1929-1933). PLoS Pathogy; 12: 1, e1005271.

Gilroy R (2019) The anti-vaccination movement: a concern for public health. Practice Nursing; 30: 5, 248-249.

Heath P, McVernon J (2002) The UK Hib vaccine experience. Archives of Disease in Childhood; 86: 396-399.

Hussain A et al (2018) The anti-vaccination movement: a regression in modern medicine. Cureus; 10: 7, e2919.

Jackson LA et al (2020) A SARS-CoV-2 mRNA vaccine preliminary report. New England Journal of Medicine; 383: 20, 1920-1931.

Jain D, Salunke DM (2019) Antibody specificity and promiscuity. Biochemical Journal; 476: 3, 433-447.

Liu MA (2019) A comparison of plasmid DNA and mRNA as vaccine technologies. Vaccines; 7: 2, 37.

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Mahase E (2020b) Covid-19: UK approves Pfizer and BioNTech vaccine with rollout due to start next week. British Medical Journal; 371: m4714.

Murtaza M et al (2016) Diphtheria: clinical manifestations, diagnosis, and role of immunization in prevention. IOSR Journal of Dental and Medical Sciences; 15: 10, 9790/0853-1508037176.

NHS (2019a) BCG Tuberculosis (TB) Vaccine Overview. NHS.

NHS (2019b) 6-in-1 Vaccine Overview. NHS.

NHS (2019c) 4-in-1 Pre-school Booster Overview. NHS.

NHS (2019d) 3-in-1 Teenage Booster Overview. NHS.

Ratajczak W et al (2018) Immunological memory cells. Central-European Journal of Immunology; 43: 2, 194-203.

Riedel S (2005) Edward Jenner and the history of smallpox and vaccination. Proceedings (Baylor University Medical Center); 18: 1, 21-25.

Silverstein A (2002) The Clonal Selection Theory: what it really is and why modern challenges are misplaced. Nature Immunology; 3: 793-796.

Vaccine Knowledge Project (2019) The UK Immunisation Schedule. Oxford Vaccine Group.

Vidarsson G et al (2014) IgG subclasses and allotypes: from structure to effector functions. Frontiers in Immunology; 5: 520.

Wakefield AJ et al (1998) Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. The Lancet; 1998: 351, 637-641.

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Zheng YQ et al (2015) Applications of bacillus Calmette-Guerin and recombinant bacillus Calmette-Guerin in vaccine development and tumor immunotherapy. Expert Review of Vaccines; 14: 9, 1255-1275.

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The lymphatic system 5: vaccinations and immunological memory - Nursing Times

Immunology

Lonza Announces High-Quality Cryopreserved Leukopaks for More Flexibility in Immunology and Cell Therapy Research – BioSpace

Quote from Andrew Winner, Product Manager, Lonza Bioscience:"The short viability window of fresh Leukopaks means researchers are at the mercy of donor and shipping schedules and any logistical delays can wreak havoc on project costs and the quality of research results. By offering cryopreserved Leukopaks, we are expanding our ability to deliver high-viability cell products internationally, and the rapid availability of stored cryopreserved Leukopaks means our customers are better able to adhere to uncompromising research timelines."

Basel, Switzerland, 28 January 2021 Lonza has expanded its renowned human primary cell offerings with the launch of fully customizable, high-quality cryopreserved Leukopaks. The frozen Leukopaks will enable long-distance shipping of leukapheresis products without the concern of reduced cell viability encountered with fresh Leukopaks. Being suitable for long-term storage in research labs, the cryopreserved Leukopaks will also allow immediate access to viable cells for greater convenience and workflow flexibility. The cryopreserved Leukopaks come in a range of sizes, and multiple donor characteristics and testing options are available through a unique costing structure that allows customers to only pay for the customization that they need.

A Leukopak is an enriched leukapheresis-derived product containing high concentrations of peripheral blood mononuclear cells like T cells, B cells and monocytes. Such cells are a critical raw material in immunotherapy research and for optimizing cell therapy process development before progressing to full clinical manufacture. However, fresh Leukopaks can be hard to access and must be used rapidly to avoid cell degradation. International transportation options are thus severely limited, and logistical delays or donor cancellations can have catastrophic impacts on research costs and quality. Cryopreserved Leukopaks allow reliable global shipping while maintaining cell viability and functionality, and the ability to thaw cryopreserved Leukopaks when needed means researchers are better able to plan ahead for more cost-efficient therapy development.

Lonzas cryopreserved Leukopaks are available in a range of sizes, including packs of 2.5, 5 and 9.5 billion cells, which can be subdivided into separate smaller bags for greater convenience. Specific donor characteristics like age, gender and Human Leukocyte Antigen (HLA) type are also available, with a wide range of recallable donors and several product testing options. Customization follows a unique, tailored pricing structure, where customers only pay for the customization they require. Customers will also have access to Lonzas globally renowned technical support services to facilitate optimized product usage and greater research success.

To find out more about Lonzas cryopreserved Leukopak offerings, please clickhere.

About LonzaLonza is the preferred global partner to the pharmaceutical, biotech and nutrition markets. We work to prevent illness and enable a healthier world by supporting our customers to deliver new and innovative medicines that help treat a wide range of diseases. We achieve this by combining technological insight with world-class manufacturing, scientific expertise and process excellence. These enable our customers to commercialize their discoveries and innovations in the healthcare sector.

Founded in 1897 in the Swiss Alps, today Lonza operates across three continents. With approximately 14,000 full-time employees, we are built from high-performing teams and of individual talent who make a meaningful difference to our own business, as well as to the communities in which we operate. The company generated sales of CHF 4.5 billion in 2020 with a CORE EBITDA of CHF 1.4 billion. Find out more atwww.lonza.com

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Lonza Contact Details

Dr. Sanna FowlerHead of External CommunicationsLonza Group LtdTel +41 61 316 8929sanna.fowler@lonza.com

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Additional Information and DisclaimerLonza Group Ltd has its headquarters in Basel, Switzerland, and is listed on the SIX Swiss Exchange. It has a secondary listing on the Singapore Exchange Securities Trading Limited ("SGX-ST"). Lonza Group Ltd is not subject to the SGX-STs continuing listing requirements but remains subject to Rules 217 and 751 of the SGX-ST Listing Manual.

Certain matters discussed in this news release may constitute forward-looking statements. These statements are based on current expectations and estimates of Lonza Group Ltd, although Lonza Group Ltd can give no assurance that these expectations and estimates will be achieved. Investors are cautioned that all forward-looking statements involve risks and uncertainty and are qualified in their entirety. The actual results may differ materially in the future from the forward-looking statements included in this news release due to various factors. Furthermore, except as otherwise required by law, Lonza Group Ltd disclaims any intention or obligation to update the statements contained in this news release.

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Lonza Announces High-Quality Cryopreserved Leukopaks for More Flexibility in Immunology and Cell Therapy Research - BioSpace

Immunology

Assistant/Associate Professor in Immunology job with UNITED ARAB EMIRATES UNIVERSITY | 243125 – Times Higher Education (THE)

Job Description

The Department of Medical Microbiology & Immunology, College of Medicine and Health Sciences (CMHS), UAE University, seeks candidates for a faculty position at the rank of Assistant/Associate Professor in Immunology. Outstanding candidates working in all areas of immunology are invited to apply. We are particularly looking for an innovative investigator with a strong research productivity who has an established, or a clear potential to establish, an independent research program.

Candidates with experience in translational immunology research and with a strong background in computational and systems biology, genomics or bioinformatics will be preferred. Screening of applications will continue until the position is filled. The College of Medicine operates an internationally recognized, integrated, problem/team-based learning curriculum and provides excellent research facilities. English is the language of instruction. Areas of research within the Department include integrative immunology approaches to study cancer immunity and immunotherapy, mechanisms of autoimmune disorders, molecular epidemiology of human bacterial pathogens and antibiotic resistance, development of retroviral vectors for gene therapy, EBV and its role in the pathogenesis of human diseases and public health, neuroimmune regulatory pathways, and host-pathogen interactions.

Minimum Qualification

The successful candidate must have a PhD or MD/PhD from an accredited institution. The candidate should have a strong track record of research in immunology. It is expected that the appointee will also have experience in teaching medical and postgraduate students. Importantly, candidates must demonstrate the potential to establish an independent and sustained research program in their area of expertise and be able to obtain peer-reviewed internal and external funding.

Preferred Qualification

As above.

Division College of Medicine&Health ScienceDepartment Microbiology - (CMHS)Job Close Date open until filledJob Category Academic - FacultySalary 30000-40000 UAE Dirhams per month, based on experience

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Assistant/Associate Professor in Immunology job with UNITED ARAB EMIRATES UNIVERSITY | 243125 - Times Higher Education (THE)

Immunology

Immunology, immunopathogenesis and immunotherapeutics of COVID-19; an overview – DocWire News

This article was originally published here

Int Immunopharmacol. 2021 Jan 5;93:107364. doi: 10.1016/j.intimp.2020.107364. Online ahead of print.

ABSTRACT

Coronavirus disease 2019 (COVID-19) infection which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to a public health emergency of international concern (PHEIC). The infection is highly contagious, has a high mortality rate, and its pathophysiology remains poorly understood. Pulmonary inflammation with substantial lung damage together with generalized immune dysregulation are major components of COVID-19 pathogenesis. The former component, lung damage, seems to be at least in part a consequence of immune dysregulation. Indeed, studies have revealed that immune alteration is not merely an association, as it might occur in systemic infections, but, very likely, the core pathogenic element of COVID-19. In addition, precise management of immune response in COVID-19, i.e. enhancing anti-viral immunity while inhibiting systemic inflammation, may be key to successful treatment. Herein, we have reviewed current evidence related to different aspects of COVID-19 immunology, including innate and adaptive immune responses against the virus and mechanisms of virus-induced immune dysregulation. Considering that current antiviral therapies are chiefly experimental, strategies to do immunotherapy for the management of disease have also been reviewed. Understanding immunology of COVID-19 is important in developing effective therapies as well as diagnostic, and prophylactic strategies for this disease.

PMID:33486333 | DOI:10.1016/j.intimp.2020.107364

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Immunology, immunopathogenesis and immunotherapeutics of COVID-19; an overview - DocWire News

Immunology

Scientists Find Key Function of Molecule in Cells Crucial for Regulating Immunity – Newswise

Newswise CHAPEL HILL, NC Many molecules in our bodies help our immune system keep us healthy without overreacting so much that our immune cells cause problems, such as autoimmune diseases. One molecule, called AIM2, is part of our innate immunity a defense system established since birth to fight pathogens and keep us healthy. But little was known about AIM2s contribution to T cell adaptive immunity defenses developed in response to particular pathogens and health problems we develop over the course of our lives.

Now, UNC School of Medicine scientists co-led by Jenny Ting, PhD, the William Kenan Distinguished Professor of Genetics, and Yisong Wan, PhD, professor of microbiology and immunology, discovered that AIM2 is important for the proper function of regulatory T cells, or Treg cells, and plays a key role in mitigating autoimmune disease. Treg cells are a seminal population of adaptive immune cells that prevents an overzealous immune response, such as those that occurs in autoimmune diseases.

Published in Nature, the research shows that AIM2 is actually expressed at a much higher level in Treg cells of the adaptive immune system than in innate immune cells.

Our study unveils an unexpected and previously unappreciated role for AIM2 in Treg cells in adaptive immunity, which is independent of AIM2s classic function in the innate immunity, said Ting, co-senior author of the study, member of the UNC Lineberger Comprehensive Cancer Center, and director of the Center for Translational Immunology.

Wan, co-senior author and member of the UNC Lineberger Comprehensive Cancer Center, added, Because Treg cells are well-known players in a broad range of diseases including autoimmunity, inflammation, and cancers, our findings will help us identify new molecular targets and develop new therapeutic strategies to test against debilitating and fatal diseases.

Normal immune responses are carried out by both innate immunity and adaptive immunity to fight pathogens and maintain biological stability. But these responses need to be regulated so they do not escalate and cause a whole host of different health problems aside from what the pathogen originally caused. Distinct cell types and molecules play discrete roles in the down-regulation of innate immunity and adaptive immunity. This work shows that AIM2, in Treg cells, is one of them. Treg cells dampen over-exuberant immune responses, and so they are critical for the check-and-balance of the immunity system.

Impaired function of Treg cells often perturbs immune system stability and can trigger autoimmune and inflammatory diseases.

In lab experiments led by first author Wei-Chun Chou, PhD, research associate in the Ting Lab, the UNC scientists found that AIM2 was expressed at a much higher level in Treg cells than in innate immune cells, in both mice and humans.

This suggests a big role for AIM2 in Treg cells, Chou said. We found that AIM2 is important to maintain the normal function of Treg cells, which could not effectively protect mice from developing autoimmune encephalomyelitis and inflammatory colitis without AIM2.

Those two conditions are models of the human diseases multiple sclerosis and colitis.

We conducted further molecular and biochemical analysis to reveal a new, cellular signaling pathway of protein molecules in Treg cells called the AIM2-RACK1-PP2A-AKT pathway which regulates the metabolism and function of Treg cells to mitigate autoimmune disease.

Co-first author Zengli Guo, PhD, a research associate at the UNC Lineberer Comprehensive Cancer Center and in the UNC Department of Microbiology and Immunology, added, Essentially, AIM2 restrains AKT phosphorylation, an important biological process but one that needs to be regulated.

As a result of these studies, these investigators hope to modulate the expression or function of molecules in the AIM2 signaling pathway in human Treg cells to eventually affect the outcome of diseases such as cancer or autoimmune disorders.

Other authors are: Xian Chen, Maureen Su, Song Zhang, Leslie Freeman, Meng Deng, W. June Brickey, Stephanie Montgomery, Yan Wang, Elena Eampanelli, Sara Gibson, Zianming Tan, Ling Xie, Kaixin Liang, Ge Zhang, Liang Chen, and Hao Guo.

Funding for this research: National Institutes of Health, the National Multiple Sclerosis Society, UNC Lineberger, and a Yang Family Biomedical Scholar Award to Yisong Wan.

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Scientists Find Key Function of Molecule in Cells Crucial for Regulating Immunity - Newswise

Immunology

Orange County native and lead scientist for Moderna vaccine honored by county – The Daily Tar Heel

One of the lead scientists who developed Moderna's coronavirus vaccine is a UNC alumna and an Orange County native.

Kizzmekia Corbett is a graduate of Orange High School and UNC's doctoral program in microbiology and immunology.

It goes without saying that this is home, Corbett said at a Jan. 19 Orange County Board of Commissioners meeting, where she was honored by the board declaring Jan. 20 "Dr. Kizzmekia S. Corbett Day." Corbett was also honored by the towns of Hillsborough and Carrboro.

Early life

During her time at Orange High School, Corbett trained as a junior researcher in UNC's Kenan Laboratories while in theProject SEED program.

She went on to attend the University of Maryland-Baltimore County as a Meyerhoff Scholar, receiving a bachelor's degree in biological sciences. While attending UMBC, Corbett studied respiratory syncytial virus and focused on why vaccines had not been effective against it.

From 2006 to 2007, Corbett worked as a lab tech in Susan Dorseys lab at the University of Maryland's School of Nursing.

What we always say is you cant train passion for research, Dorsey said. I can train you to do anything, but that passion and that dedication, that resilience, is not trainable. We all saw that very early on and we thought, The skys the limit."

After receiving her bachelors degree, Corbett attended UNC, where she got her doctorate in microbiology and immunology. While at UNC, Corbett studied dengue fever, a virus that had proved difficult to create a vaccine for.

She also worked with professor Ralph Baric, someone Corbett described as one of the best coronavirus virologists in the world.

He studied coronavirus evolution, and it was very clear even in 2014 when I left UNC that coronaviruses had this potential to cause pandemics, Corbett said at the Jan. 19 BOCC meeting.

The U.S. government wasnt paying enough attention to coronaviruses, she said, which is why she decided to join the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases.

Baric said there is hope the vaccine developed by Corbett and others at the Vaccine Research Center will make a difference.

She has a real sense for not only the basic science part of what we do, but the personal side of how infectious diseases really impact people on the ground at all social levels, Baric said. Thats a rare insight that many of us dont get to achieve.

COVID-19 pandemic

In January 2020, Moderna announced it would be partnering with the National Institute of Health to develop a coronavirus vaccine in the Vaccine Research Center. Clinical trials for the vaccine began in March.

Dr. Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases and a prominent scientist during the pandemic, praised Corbett in a conference hosted by the National Urban League last December.

Kizzy is an African American scientist who is right at the forefront of the development of the vaccine, Fauci said. So the first thing you might want to say to my African American brothers and sisters is that the vaccine you are going to be taking was developed by an African American woman, and that is just a fact.

Since the Moderna vaccine was given emergency use authorization by the FDA in December, Corbett has been raising public support for the vaccine, especially within Black communities that have been historically marginalized for the sake of science.

Chapel Hill may be seeing more of Corbett in the future, as she revealed at the meeting that she is being recruited by UNC to become a professor. She has not yet announced whether she will be accepting the position.

For now, Corbett can be found on Twitter, where she posts regular vaccine updates often accompanied by a GIF.

@trevorwmoore

@DTHCityState | city@dailytarheel.com

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Orange County native and lead scientist for Moderna vaccine honored by county - The Daily Tar Heel

Immunology

Cross Reactivity Seen Between SARS-CoV-2 and Antibodies to 2003 SARS Outbreak Virus – Technology Networks

A new study demonstrates that antibodies generated by the novel coronavirus react to other strains of coronavirus and vice versa, according to research published today by scientists from Oregon Health & Science University.

However, antibodies generated by the SARS outbreak of 2003 had only limited effectiveness in neutralizing the SARS-CoV-2 virus. Antibodies are blood proteins that are made by the immune system to protect against infection, in this case by a coronavirus.

The study published today in the journal Cell Reports.

Our finding has some important implications concerning immunity toward different strains of coronavirus infections, especially as these viruses continue to mutate, said senior author Fikadu Tafesse, Ph.D., assistant professor of molecular microbiology and immunology in the OHSU School of Medicine.

Given the speed of mutations estimated at one to two per month its not surprising that an antibody generated from a virus 18 years ago provides a meager defense against the new coronavirus. Nonetheless, Tafesse said the findings suggest more work needs to be done to determine the lasting effectiveness of COVID-19 vaccines.

I dont think there is any one size-fits-all vaccine, he said. Although the vaccines coming out now may break the momentum of the virus and end the pandemic, they may not be the end game.

Tafesse noted that researchers used individual antibody clones to test cross-reactivity, and that a bodys normal immune system will generate many antibodies that are more likely to neutralize a wider series of targets on the mutating virus.

Im not personally terribly concerned, said lead author Timothy Bates, a fourth-year molecular microbiology and immunology graduate student in the OHSU School of Medicine. Emerging mutant viruses may have some propensity to escape certain antibodies raised by previous infection or vaccine.

Every individual has a different immune system that will make a unique repertoire of different antibodies that bind to different places on the virus, so the chance of any one SARS-CoV-2 variant escaping from all of them is quite low.

The study also suggests that efforts to accurately discern a previous COVID-19 infection, by analyzing antibodies in blood, may be confounded by the presence of antibodies reacting to other strains of coronavirus including the common cold. Although this complicates diagnosis of older infections, researchers say the finding actually expands scientists ability to study the biology and disease-causing effects of the SARS-CoV-2 virus since they know it reacts to antibodies of multiple strains of coronaviruses.

It provides more tools to study the biology of this virus because we have very limited reagents available right now for SARS-CoV-2, Tafesse said.

ReferenceBates TA, Weinstein JB, Farley S, Leier HC, Messer WB, Tafesse FG. Cross-reactivity of SARS-CoV structural protein antibodies against SARS-CoV-2. Cell Reports. Published online January 2021:108737. doi:10.1016/j.celrep.2021.108737

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Cross Reactivity Seen Between SARS-CoV-2 and Antibodies to 2003 SARS Outbreak Virus - Technology Networks

Immunology

Nirogy Therapeutics Launches with $16.5 Million Series A FinancingProceeds to support the development of small-molecule drugs that modulate the…

BOSTON, Jan. 26, 2021 (GLOBE NEWSWIRE) -- Nirogy Therapeutics Inc., a privately-held biotechnology company developing novel small molecules to target cellular transporters, today announced the closing of a $16.5 million Series A financing. The financing was co-led by Sant Ventures and Sporos. In conjunction with the financing, Dennis McWilliams of Sant and Joseph Kekst of Sporos will join Nirogys board of directors, and Casey Cunningham, Ph.D. will join Nirogys scientific advisory board.

Nirogy plans to use the proceeds to advance its drug discovery platform to generate a pipeline of small-molecule drugs designed to target the solute carrier family of transporter proteins (SLCTs) embedded in the cell membrane. SLCTs are gatekeepers of essential physiological functions, including nutrient uptake and metabolite disposal, which are aberrantly altered in many diseases. Enabled by its proprietary small-molecule compound library and rapid development strategies, Nirogy is developing first-in-class medicines with an initial focus on oncology and autoimmune diseases.

Cellular transporters, which are central to many aspects of cell biology and dysregulated in myriad diseases, have not been effectively targeted due to the complex structures of SLCTs. Our teams strength in computational modeling, medicinal chemistry and cancer biology has enabled us to overcome the challenge of drugging these critical untapped targets, said Vincent Sandanayaka, Ph.D., founder, president and chief executive officer of Nirogy Therapeutics. We are fortunate to have a world-class scientific advisory board, highly committed investor partners and a dedicated team with proven scientific and drug development expertise.

Nirogys lead program targets lactate transporters for the treatment of cancer and is expected to enter human clinical trials in 2022. Unlike normal cells, cancer cells consume large amounts of glucose and excrete a huge excess of lactic acid to the tumor microenvironment via lactate transporters for their rapid growth and survival. Lactate-rich tumors create a hostile environment for immune cells to survive, thus suppressing anti-tumor immunity. Nirogys lactate transport inhibitors have shown robust anti-tumor efficacy in preclinical models, either as monotherapy or combination therapy. Nirogys pipeline also includes a second transporter target in cancer and a third program in immunology.

Dennis McWilliams, partner at Sant Ventures, said: We recognize the potential of the Nirogy team and its proprietary drug discovery engine in SLCTs, which could yield over 450 potential druggable targets and open up new treatment modalities for a number of life-threatening diseases.

Ronald DePinho, M.D., Nirogy co-founder and chair of the Sporos strategic advisory board, added: It is a privilege to work with this incredible team thats focused on revealing the mysteries of cellular transport biology and converting such insights into medicines for our patients in need.

ABOUT NIROGY

Nirogy Therapeutics is a biotechnology company based in Boston, MA developing novel small molecules to target cellular transporters. The company is currently advancing a class of small molecules intended to disrupt metabolic and immune mechanisms operative in the tumor microenvironment. Follow-on platform programs are targeting additional disease pathways in oncology as well as autoimmune diseases.

For more information, please visitnirogytx.com.

ABOUT SANTE VENTURES

Founded in 2006, Sant Ventures is a specialized healthcare and life sciences investment firm with over a half-billion dollars in capital under management. The firm invests in early-stage companies developing innovative new medical technologies, biotechnologies, and digitally enabled healthcare services. Recent Sant successes include Claret Medical (Boston Scientific), TVA Medical (Becton Dickinson), Millipede Medical (Boston Scientific), Molecular Templates (MTEM), AbVitro (Celgene), and Explorys (IBM Corp). Sant invests nationally and has offices inAustin, TX andBoston, MA.For more information, please visitsante.com.

MEDIA CONTACT:

Grace FotiadesLifeSci Communications+1. 646.876.5026gfotiades@lifescicomms.com

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Nirogy Therapeutics Launches with $16.5 Million Series A FinancingProceeds to support the development of small-molecule drugs that modulate the...

Immunology

BioAesthetics and Tulane awarded grant to develop new advanced wound-care graft – News from Tulane

BioAesthetics founder and CEO Nick Pashos, PhD, and Dr. Lisa Morici, PhD, associate professor of microbiology and immunology at Tulane University School of Medicine.

The National Science Foundation has awarded a $250,000 grant to BioAesthetics Corp. todevelop a new advanced wound-care product for treating bed sores or pressure ulcers. The product will be testedat Tulane University.

TheSmall Business Technology Transfer (STTR) Phase I award will fund initial testing and development of a skin graft that combines the companys tissue regeneration technology with infection-fighting drugs to better promote healing.

BioAesthetics founder and CEO Nick Pashos, PhD, and COO Billy Heim, are both Tulane alumni. BioAesthetics was spawned at Tulane in 2015 to commercialize a pioneering tissue graft Pashos, a Tulane student at the time, developed to regenerate a nipple and areola in breast reconstruction surgery after a mastectomy.

Lisa Morici, PhD, associate professor of microbiology and immunology at Tulane University School of Medicine, will lead testing for the study at Tulane.

Severe bed sores are particularly difficult to heal and primarily affect the elderly or those who are bed-ridden. These pressure ulcers are open wounds on the skin, commonly in bony areas like the hip, back or ankles, caused by prolonged pressure on the skin from staying in the same position. The condition affects more than 2.5 million a year.

Current treatment options involve surgical reconstruction with skin or skin substitute grafts, which can fail to heal the pressure ulcer because of infection or because the graft was not strong enough. TheBioAesthetics graft is stronger,releases medication at the surgical site to fight infection, and is designed to accelerate wound healing.

Like the companys product for breast reconstruction, the new graft uses decellularized tissue that acts as a collagen scaffold for new cells to easily grow into as the wound heals.

The underlying technology of the proposed solution can be used to make novel grafts for treatment of numerous wound types, improving healing and patient quality of life, Pashos said.

Researchers at Tulane will test the acellular biologic graft, which is strengthened with a polymer hydrogel, to see how effectively it releases the medication over a 14-day period. The study will measure the drug release and bioactivity in vitro and, using a mouse model, assess its efficacy against a common antibiotic-resistant bacterium.

Adding a biocompatible polymer to an acellular biologic graft for therapeutic applications is a unique approach that hasnt been done before, Morici said. The goal is to have a regenerative graft that can also prevent the most common complications during wound healing.

The National Science Foundations STTR program focuses on transforming scientific discovery into products and services with commercial potential and/or societal benefit. Unlike fundamental research, the program supports startups and small businesses in the creation of deep technologies, getting discoveries out of the lab and into the market.BioAesthetics is developing new products for use in reconstructive surgeries through its mission to transform lives through advancements in biomaterials.

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BioAesthetics and Tulane awarded grant to develop new advanced wound-care graft - News from Tulane

Immunology

Some Experts Claim Covid-19 Reinfections Are Not A Huge ProblemBut Nobodys Tracking The Numbers – Forbes

Doctor hand holding positive Covid-19 rapid test

Dr. Daniel Griffin, an infectious disease physician in New York, is certain hes seen multiple cases of Covid-19 reinfections. The problem is, hes just not sure how many. Were seeing a lot of people that we took care of back in the early spring returning to the hospitals with Covid-19 symptoms, he says. Other physicians that hes spoken to agree that theyve seen what seem to be Covid-19 reinfections on a regular basis, but their evidence is only anecdotal.

Krutika Kuppalli, an infectious disease physician who also treats Covid-19 patients, also believes she has seen multiple cases of reinfections. Ive had patients that Ive suspected, but theres no way to test, she says. Reinfections are definitely happening, she says, we just dont know on what scale.

According to Alessandro Sette, an immunobiologist at the La Jolla Institute for Immunology, at this point, reinfections are not a huge problem. Sette is a coauthor on a recent study published in the journal Science which suggests that a majority of patients remain immune to Covid-19 reinfection at least eight months after diagnosis.

But as the world looks forward to Covid-19 vaccines and reliable treatments to recover from nearly a year of locking down, those missing numbers could be hiding the true story about how long vaccinations will last, and whether the pandemic can be brought under control as the virus evolves more contagious strains.

The number of patients suffering Covid-19 reinfections is likely a small percentage of the hundreds of thousands of new infections diagnosed worldwide daily, immunologists suggest. The only place that seems to be even attempting to track reinfections is a Dutch news site that has counted over 9,000 cases of suspected reinfection. But to know for sure would require a genetic sequence of the virus in both the first and second diagnosis to compare whether the new infection is a genetically distinct virus or the same from the original infection. Countries such as Australia and Taiwan are doing routine sequencing, which could teach scientists more about the Covid-19 immunity as well as new, more contagious variants of Covid-19. On the U.S. frontlines however, most doctors just dont have the time or resources to be sequencing thousands of viral genomes each day. Were swamped, Griffin says, were trying to keep people alive.

Currently, the U.S. ranks as 43rd worldwide when it comes to genomic sequencing of Covid-19. The United States is not doing enough, says Jessica Malaty Rivera, the communications lead for The COVID Tracking Project. Rivera says that she doesnt believe states are tracking it on a local level, and there is no central database where physicians across the country can report suspected or confirmed cases of reinfections. The only way to properly track reinfections is to do much more genomic sequencing than were doing, she says. Only then will the true scope of Covid-19 reinfections be made clear.

Sette says that reinfections are likely to be mild cases compared to initial cases of the disease though thats not always true. An article published in medical journal the Lancet last October detailed a case of Covid-19 reinfection of a 25-year old man in Nevada whose second infection was more severe than his first. Griffin says he has also personally seen at least one case of reinfection where the first infection was beaten at home, but the patient had to be hospitalized to treat the second infection. This is where better data would reveal the true story.

Tracking reinfections would also teach scientists more about the new, more contagious variants of Covid-19 that are currently circulating the globe. Current data indicates that some of these SARS-CoV2 lineages might have a higher capacity to reinfect people, says Ramon Lorenzo Redondo, a professor of infectious diseases at Northwestern. But more research is needed. Of particular concern is a Covid-19 variant, first discovered in South Africa and now in more than 30 countries, including the U.S. which may prevent patients from developing immunity. But, he says, I dont believe that any of the initial concerns about reinfections have amounted to much so far.

It will matter down the road, however. Knowing how many reinfections are actually occurring provides valuable clues to how long natural immunity to Covid-19 actually lasts. Stanley Perlman, a coronavirus researcher at the University of Iowa, expects that immunity to Covid-19 begins to wane anywhere from between 6 months to a year. Reinfections would be a key indicator of that, he notes, adding I think what one can say is its not permanent immunity.

This article was updated at 6:30pm ET on 1/29/21 for clarity

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Some Experts Claim Covid-19 Reinfections Are Not A Huge ProblemBut Nobodys Tracking The Numbers - Forbes