Vaccines and the immune response
A vaccine initiates innate and adaptive immunity to build long-term immunological memory against a pathogen, without causing the disease, and an adjuvant enhances and modulates the immunogenicity of the vaccine's antigens. A preventive vaccine protects a healthy person before exposure, and a therapeutic vaccine treats a disease already present. Because vaccines are given to large populations of healthy people, their benefit-risk profile has to be highly favourable. Allergen immunotherapy is now considered a type of therapeutic vaccination.
How a vaccine works
Vaccines act by initiating innate and adaptive immunity to produce long-term immunological memory against disease-causing pathogens. A vaccine trains the immune system to recognise and handle harmful pathogens. It does so by stimulating the production of specific antibodies, which produces immunity to a disease. Human immunity needs some stimulation from an outside source to emerge. A vaccine gives a person a way to recognise a threatening pathogen and mobilise their own resources to conquer a miniature form of it, so that the full pathogen does not come as a surprise. A person exposed to a pathogen through a vaccine has an immune memory of it and can call on the memory of defeating the miniature pathogen to neutralise the full one. A person whose vaccination enables an immediate response has a strong chance of gaining the upper hand on the pathogen, which will not have time to make a full-scale attack.
Unlike a natural infection, a vaccine does not cause the disease, because it contains only inactivated or attenuated micro-organisms or, in a subunit vaccine, selected antigenic fragments from pathogens. Some vaccines expose the body to a weakened or attenuated live form of the pathogen, such as measles virus, or to an inactivated form of it, such as hepatitis A virus. Others expose the body to a minimally dangerous pathogen that invokes an immune response able to neutralise a more dangerous one, such as cowpox virus, which is used to vaccinate people against smallpox. Vaccines are prepared from the disease pathogen or its products, or from synthetic substitutes that act like antigens without inducing disease. They are typically administered by injection, orally or by aerosol. Vaccine development has progressed significantly, from empirical design in its early days to rational design based on the biology of the targeted infection and of the disease to be prevented.
Preventive and therapeutic vaccines
A preventive or prophylactic vaccine, given before exposure to a disease, enables the body to build protective mechanisms against infection while the person is still healthy, averting future illness. Examples include vaccines against meningitis, influenza, polio, smallpox, measles, rubella and hepatitis. A therapeutic vaccine treats disease in infected people by stimulating the immune system to target diseased cells, which improves the immune response and enables the body to curb or exterminate a pathogen.
Adjuvants and booster doses
A vaccine adjuvant is a substance that enhances and modulates the immunogenicity of the vaccine's antigens and increases the magnitude and durability of the immune responses the vaccine elicits. An adjuvant may be added to a candidate vaccine to make it more effective. Adjuvants can be just as important in vaccine design as the vaccine antigen itself. They are used to activate innate immunity, improve memory responses, and broaden or extend innate and adaptive immune responses. This can help to reduce the amount of antigen per dose or the number of doses needed for a given vaccine. Subunit vaccines usually require adjuvants, because they contain fewer antigens and may lack some molecular components of whole pathogens that trigger innate immune cells.
In the prime-boost technique of vaccination, booster doses are given after vaccination with a primary vaccine to prolong the durability of protection and counteract the inadequacy of primary vaccination alone, whose effect wanes.
Benefits and safety
Vaccines are among the greatest triumphs in public health of recent times. They are the safest and most cost-effective way to prevent and eliminate infectious diseases, disability and death. As of 2018, they saved 2 million to 3 million lives each year. They had substantially reduced the incidence of several major diseases, such as polio and measles, in the few decades before 2018. In 2018, licensed vaccines were available for preventing more than 30 different infectious diseases, several of which can be combined or administered at the same vaccination visit.
Because vaccines are given as preventive measures to large populations of healthy individuals, especially infants and children, a highly favourable benefit-risk profile is essential. When adverse events do occur, they are usually mild and transient and typically centred at the injection site, such as injection-site pain, redness and swelling. Mild and transient systemic reactions, such as headache and fever, can also occur with some vaccines.
Allergen immunotherapy
Allergen immunotherapy modulates the immune system to prevent and relieve allergic symptoms. Unlike allergen avoidance and medication to control symptoms, such as antihistamines and corticosteroids, it targets the underlying pathophysiology of allergic diseases. It is now considered a type of therapeutic vaccination, because it uses antigens to treat an existing illness by modulating the immune system.
Allergen immunotherapy is indicated in patients whose allergies interfere with daily activities or sleep despite allergen avoidance and medication, who have moderate-to-severe allergic symptoms when exposed to an aeroallergen, and who are sensitised to allergen-specific immunoglobulin E. These patients often also have asthma.
In allergen immunotherapy, the allergen is administered subcutaneously or sublingually at regular intervals to modulate the immune response. The aim is to reduce associated symptoms, decrease the need for medication, and prevent the development of new allergies and asthma.
Traditionally, allergen immunotherapy products contain allergens isolated from biological sources such as pollen or house dust mites, which can be used unmodified or denatured with aldehydes and may be mixed with an adjuvant. Allergen products for subcutaneous immunotherapy are mainly applied as depot formulations, meaning that the drug is injected as a localised mass. Subcutaneous immunotherapy is given in escalating doses every 7 and 14 days for depot solutions and every 3 to 7 days for aqueous solutions. Once the maximum tolerated dose is reached, the injection intervals can be extended to every 4 to 8 weeks. In one example schedule, increasing doses are applied every 7 days during a dose-escalation phase until the maximum tolerated dose is reached, followed by a maintenance phase of 3 to 5 years. For airway allergies, such as allergy-induced asthma, the overall duration of subcutaneous immunotherapy should be at least 3 years.