Immune enhancers and allergy

Allergies are usually associated with an imbalance and an over-dominant Th2 response. In essence, the immune system gets the wrong message and “sees” a perfectly harmless antigen such as found in pollens or house dust mites as if coming from a tapeworm or other parasite.

The Th2 controlled response involves recruiting inflammatory cells, particularly eosinophils and mast cells and the production of IgE against the antigen (allergen). These work together to release a cocktail of inflammatory chemicals including histamine from mast cells and cytotoxic chemicals from eosinophils, which produce the swelling and redness associated with allergic reactions. Allergic reactions in the nose and nasal passages produce the symptoms experienced by hay fever sufferers called allergic rhinitis. This typically includes swelling and blockage of the nasal passages and increased mucus secretion and a runny nose. Similar reactions in the delicate cornea result in conjunctivitis.

Continual exposure to aeroallergens can lead to inflammation in the lungs. Over time this can result in chronic changes in lung tissue, hyper-reactivity to a variety of stimuli, constriction of airway smooth muscle and excessive mucus secretion leading to obstruction of airways. Asthma is a serious disease and is a disease on the increase in developed countries.

Immune enhancers shift the balance in favour of a Th1 controlled immune response and re-trains the Th controlling cells to respond with a non-allergic response. In essence the immune enhancer provides the secondary signals that allow the immune system to “see” the allergen as being microbial rather than of parasitic origin. As balance is restored, other regulatory T lymphocytes develop that reduce the overall responsiveness of the immune system to the allergens, inducing a state of immune tolerance.

Scientific papers
Intranasal application of chitin microparticles down-regulates symptoms of allergic hypersensitivity to Dermatophagoides pteronyssinus and Aspergillus fumigatus in murine models of allergy. Download PDF

Treatment with chitin microparticles is protective against lung histopathology in a murine asthma model. C. Ozdemir, D. Yazi, M. Aydogan, T. Akkoc, N. N. Bahceciler, P. Strong , and I. B. Barlan. Download PDF

Immune enhancers and infection

The lungs are a major portal of entry for pathogenic and non-pathogenic bacteria, viruses and fungal spores. The ability to fight off infections depends on a healthy and robust immune system in the nasal and respiratory mucosal membranes. The early response is vital to stop the microbes becoming established and to prevent them proliferating. This first line defence is referred to as the Innate Immune system. The major effectors of this first line defence are the phagocytic cells – the macrophages, dendritic cells and natural killer cells (NK cells). These not only directly recognise and destroy microbes but also produce the warning signals to galvanise the immune system to respond. The principle cytokines that do this are IL-12 produced by phagocytes when they encounter microbes and IFNg produced by NK cells either directly or when activated by IL-12. These cytokines set in action a series of events that result in the attraction of activated effector cells, including more macrophages and neutophils to the sight of infection.

Immune enhancers, which are often the by-products of microbes, provide a method of stimulating and activating the defensive response against potential infection. This is of particular importance for those with a weak immune system – the elderly, or those with a chronic disease such as AIDS or cystic fibrosis. There would also be beneficial to strengthen the immune system of children, whose immune system is in the early stages of development.

Scientific Paper
Prophylactic Effects of Chitin Microparticles on Highly Pathogenic H5N1 Influenza Virus. Download PDF

Immune enhancers as vaccine adjuvants

The development of vaccines represents perhaps the single greatest advance in medicine. The world wide market for vaccines was $5 billion in 2000 and is expected to reach $15 billion by 2010.  Currently all vaccines are prophylactic, but it is expected that in the next few years we will see an explosion in therapeutic vaccines for treating ongoing diseases such as AIDS, cancer and allergies.

Therapeutic vaccines are based on the sound concept of eliciting the powerful disease fighting capabilities of the immune system and enhancing this. A vaccine is composed of one or more antigens, typically a bacterial or viral protein, and the vaccine is designed to stimulate the generation of neutralizing antibodies against the antigens as well as producing memory T and B cells, which can be quickly activated if there should be a subsequent infection. However, antigens alone are typically insufficient to achieve protective immunization and in fact this is part of the body’s strategy not to respond to every encounter with the billions of foreign molecules that are encountered in our environment.

A vaccine adjuvant is a substance often of microbial origin that enhances, accelerates, modifies or prolongs specific immune responses to the antigens such that the vaccine itself achieves acceptable performance, good efficacy at minimal antigen dose and dosage schedule. Many of the best prophylactic vaccines are either live attenuated viruses or bacteria for measles, mumps and polio or killed bacteria such as the pertussis vaccine against whooping cough and inactivated flu virus vaccines to protect against flu. Clearly these vaccines contain the natural adjuvants components of the bacteria or virus, which make them very effective. For other antigens, it is necessary to add an adjuvant. The DTP triple vaccine is an interesting example in which the high adjuvant property of the killed pertussis bacterium is combined with diptheria and tetanus toxoids, both of which are not very immunogenic by them selves.

Nasal Vaccines
Of course most vaccines are designed for injection. However, injection based vaccination has two disadvantages, the first practical and the second immunological. Injections are painful and expensive and require a level of sterility that is not always practical as well as medical staff to administer the injections. Barriers to compliance are a serious issue with mass vaccination programmes, which are often necessary to achieve target levels of herd immunity.

The immunological drawback is that injection is not the usual route of entry for the majority of pathogens. A more typical route of infection is through the mucosal surfaces of the respiratory tract or gut. For example, the highly successful live attenuated Sabin polio vaccine is taken orally and protects against polio virus, which is transmitted through fecal contamination. The mucosal surfaces have evolved a specific immune system that is quite unique and specialized to deal with pathogens such as influenza virus, rhinovirus and a host of other air borne pathogens as well as non-pathogenic microbes. For this reason there has been a great deal of interest in developing nasal vaccines for flu and other respiratory pathogens. On the practical side, nasal vaccines are easy to use and provide good solutions for the rapid mass vaccination required to deal with flu epidemics and other such threats.

Scientific Papers
Protection against influenza virus infection by intranasal administration of hemagglutinin vaccine with chitin microparticles as an adjuvant. Download PDF

Chitin microparticles (CMP): A useful adjuvant for inducing viral specific immunity when delivered intranasally with an HIV-DNA vaccine. Download PDF

Intranasal administration of adjuvant-combined recombinant influenza virus HA vaccine protects mice from the lethal H5N1 virus infection. Download PDF