pink book | Principles of Vaccination | Epidemiology of VPDs (2023)

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Immunology and vaccine-preventable diseases

To understand how vaccines work and the basis for recommendations on their use, it is helpful to understand the basic function of the human immune system. The following description is simplified; Many excellent immunology textbooks provide additional detail.

Immunity is the human body's ability to tolerate the presence of endogenous substances and eliminate foreign substances. This discriminatory ability to eliminate foreign substances is performed by a complex system of interacting cells called the immune system. Because most organisms (eg, bacteria, viruses, and fungi) are identified as foreign, the ability to identify and eliminate these substances provides protection against infectious disease. Immunity is generally specific to a single organism or a group of closely related organisms.

The immune system develops a defense against antigens, which are substances that can stimulate the immune system. This defense is known as the immune response and usually involves the production of:

• Protein molecules (immunoglobulins or antibodies, the main component of humoral immunity) from B lymphocytes (B cells)
• Specific cells including T lymphocytes (aka cell-mediated immunity)

The most effective immune responses are generally generated in response to antigens present in a living organism. However, an antigen need not necessarily be present in a living organism to elicit an immune response. Some antigens such as Viruses such as hepatitis B surface antigen are readily recognized by the immune system and provide adequate protection even when not transmitted with the live hepatitis B virus. Other materials are less potent antigens and the immune response they elicit may not provide good protection.

types of immunity

There are two basic mechanisms for acquiring immunity: passive and active.

Passive Immunity

Passive immunity is protection from antibodies or antitoxins produced by one animal or human and transferred to another. Passive immunity provides immediate protection against infection, but this protection is temporary. The antibodies are broken down over a period of weeks to months and the recipient is no longer protected.

The most common form of passive immunity is that which an infant receives from the mother. Antibodies, particularly the class of antibodies called IgG, are transported across the placenta mainly during the last 1 to 2 months of pregnancy. As a result, a full-term infant has the same type of antibodies as the mother. These antibodies can protect the infant from certain diseases in the first few months after birth. Maternal antibodies provide better protection against some diseases (eg, measles, rubella, tetanus) than others (eg, polio, whooping cough).

Passive immunity can also be acquired by transfusing blood products. Some blood products (eg, washed or reconstituted red blood cells) contain a relatively small amount of antibody, while others (eg, intravenous immunoglobulin and plasma products) contain a large amount.

Besides blood products used for transfusions, there are three other important sources of antibodies used in human medicine. These are homologous pooled human antibody, homologous human hyperimmune globulin and heterologous hyperimmune serum.

Homologous pooled human antibody, also known as immunoglobulin, is made by combining the antibody fraction, specifically the class of antibodies called IgG, from the blood of thousands of adult donors. Because it comes from many different donors, it contains antibodies to many different antigens. It is mainly used for the prophylaxis of hepatitis A and measles and for the treatment of certain congenital immunoglobulin deficiencies.

Human Hyperimmunoglobulin Homologsare antibody products that contain high titers of antibodies that target more specific antigens. These products are made from donated human plasma with high levels of the antibody of interest. Since hyperimmune globulins are human derived, they are mainly polyclonal and contain many types of antibodies at lower levels. Hyperimmunoglobulins are used for post-exposure prophylaxis in several diseases including hepatitis B, rabies, tetanus and chickenpox.

Heterologes Hyperimmunserum, also called antitoxin, is produced by animals, mostly horses, and contains antibodies against only one antigen. Antitoxins are available in the United States to treat botulism and diphtheria. These products can cause serum sickness, an immune response to equine protein.

Immunoglobulin products from human sources are primarily polyclonal; they contain many types of antibodies. Monoclonal antibody products have many uses, including diagnosis of certain types of cancer (colon, prostate, ovarian, breast), treatment of cancer (B-cell chronic lymphocytic leukemia, non-Hodgkin's lymphoma), prevention of transplant rejection, and treatment of autoimmune diseases (Crohn's disease, rheumatoid arthritis) and infectious diseases.

While certain antibody products such as immunoglobulins interfere with the immune response to live virus vaccines, monoclonal antibody products do not because they are directed against an antigen or a closely related group of antigens. A monoclonal antibody product, palivizumab (Synagis), is available to prevent respiratory syncytial virus (RSV) infection. Because Synagis contains only RSV antibodies, it will not affect the response to a live vaccine.

Active Immunity

Active immunity is protection created by a person's own immune system. The immune system is stimulated by an antigen to produce antibody-mediated and cell-mediated immunity. Unlike passive immunity, which is temporary, active immunity usually lasts for many years, often for life.

One way to gain active immunity is to survive infection with the disease-causing form of the organism. In general, individuals who have recovered from an infectious disease have lifelong immunity to that disease (there are exceptions, such as malaria). The persistence of protection for many years after infection is referred to as immunological memory. After the immune system is exposed to an antigen, certain memory B cells continue to circulate in the blood and reside in the bone marrow for many years. Upon renewed exposure to the antigen, these memory cells begin to rapidly replicate and produce antibodies to restore protection.

Another way to create active immunity is vaccination. Vaccines contain antigens that stimulate the immune system to produce an immune response that often resembles that produced by natural infection. However, vaccination does not expose the recipient to the disease and its possible complications.

Many factors can influence the immune response to vaccination. These include the presence of maternal antibodies, the type and dose of antigen, the route of administration, and the presence of an adjuvant (e.g., aluminum-containing material added to improve the immunogenicity of the vaccine). Host factors such as age, diet, genetics, and comorbidities can also affect the immune response. The more similar a vaccine is to the disease-causing form of the organism, the better the immune response to the vaccine.

Classification of vaccines

There are two basic types of vaccines:

1. Live, muffled and
2. Disabled. Their properties are different and determine how each type is used.

live attenuated vaccines

Live vaccines are derived from "wild" viruses or bacteria. These wild viruses or bacteria are weakened (weakened) in a laboratory, usually through repeated cultivation. For example, the measles virus used today as a vaccine was isolated in 1954 from a child suffering from measles. Almost 10 years of serial passage with tissue culture media were required to transform wild-type virus into attenuated vaccine virus.

In order to elicit an immune response, live attenuated vaccines must be replicated in the vaccinated individual. A relatively small dose of virus or bacteria administered will replicate in the body and generate enough of the organism to stimulate an immune response.

Although live attenuated vaccines replicate, they do not usually cause diseases like those caused by the wild-type organism. When a live attenuated vaccine causes disease, it is usually much milder than the natural disease and is considered an adverse reaction to the vaccine.

The immune response to a live attenuated vaccine is virtually identical to that of a natural infection because the immune system does not distinguish between infection with an attenuated vaccine virus and infection with a wild virus. Injected live attenuated vaccines produce immunity in most recipients with one dose. However, a small percentage of recipients do not respond to the first dose of an injected live attenuated vaccine (such as measles, mumps and rubella [MMR]) and a second dose is recommended to achieve an extremely high level of immunity in the population. Orally administered live attenuated vaccines require more than one dose to produce immunity.

A live attenuated vaccine can cause serious or fatal infections as a result of uncontrolled growth of the vaccine virus or bacteria. However, this only occurs in people with a weakened immune system (eg, due to leukemia, treatment with certain drugs, or human immunodeficiency virus [HIV] infection).

A live attenuated vaccine virus could theoretically revert to its original pathogenic form. This is known to be the case only with live (oral) polio vaccines, which are no longer available in the United States.

Active immunity against a live attenuated vaccine may not develop because the vaccine virus is disrupted by circulating antibodies. Antibodies from any source (e.g., transplacental transmission to infants, transfusion of blood products) can interfere with the replication of the vaccinee and result in a weak or no response to the vaccine (also known as vaccine failure).

Live attenuated vaccines are fragile and can be damaged or destroyed by heat and light. They must be stored and handled with care. The live, attenuated viral vaccines currently available and routinely recommended in the United States are MMR, chickenpox, rotavirus, and influenza (intranasal). Other live vaccines that are not routinely recommended include adenovirus vaccine (used by the military), typhoid fever vaccine (Ty21a), and bacille Calmette-Guerin (BCG). BCG is not used as a vaccine in the United States but is used to treat bladder cancer.

Inactivated vaccines

Inactivated vaccines are not live and cannot replicate. These vaccines cannot cause disease even in an immunocompromised person. Inactivated antigens are less affected by circulating antibodies than live antigens, so they can be given when antibodies are present in the blood (eg, in infancy or after receiving antibody-containing blood products).

The immunity provided by inactivated vaccines is generally not as long-lasting as that provided by live attenuated vaccines. Multiple doses over a period of time are required to achieve sustained immunity. In general, the first dose does not create protective immunity, but rather "primes" the immune system. After the second or third dose, a protective immune response develops. Unlike live vaccines, which elicit an immune response very similar to a natural infection, the immune response to an inactivated vaccine consists primarily of the production of antibodies. Little or no cellular immunity results. Antibody titers against inactivated antigens decrease over time. As a result, some inactivated vaccines may require periodic supplemental doses to increase or "boost" antibody titers.

Inactivated vaccines include inactivated whole-cell vaccines (eg, polio, hepatitis A, and rabies vaccines), subunit vaccines (eg, influenza and pneumococcal vaccines), toxoids (eg, diphtheria and tetanus toxoid) and recombinant vaccines (eg, hepatitis B, human papillomavirus [HPV], and influenza [Flublok brand]).

Inactivated whole cell vaccinesContain bacteria or viruses that have been killed by a physical or chemical process. Whole-cell inactivated viral vaccines for polio, hepatitis A, and rabies are available in the United States. A vaccine made from killed pertussis (whooping cough) bacteria is available outside the United States.

subunit vaccinescontain some of the bacteria or viruses. The part of the organism selected is that part needed to elicit a protective immune response. Antigens in subunit vaccines can be protein, polysaccharide, or a combination of polysaccharide and protein molecule (i.e., conjugate vaccine).

Conjugated subunit vaccines (e.g.Haemophilus influenzaeType b and pneumococcal conjugate vaccines are made by chemically attaching a polysaccharide from the bacterial surface to a protein molecule through a process called conjugation. Conjugation of a polysaccharide antigen to a protein molecule produces long-lasting protective immunity against the polysaccharide antigen.

The immune response to a pure polysaccharide vaccine is typically T cell independent, meaning these vaccines can stimulate B cells without the help of helper T cells. T-cell independent antigens, including polysaccharide vaccines, are not consistently immunogenic in children under 2 years of age, probably due to immune system immaturity. Attaching the polysaccharide antigen to a protein makes it possible to prevent bacterial infections in populations where a polysaccharide vaccine is ineffective or only provides temporary protection.

toxoid vaccinesare made using inactivated toxins produced by bacteria. These protein-based toxins are inactivated by heat, chemicals, or other methods. Some bacteria (e.g. tetanus, diphtheria) cause disease by producing toxins. The immune system's ability to recognize and eliminate these toxins provides protection against the disease.

Recombinant Vaccinesare produced by recombinant DNA technology. Recombinant DNA technology allows DNA from two or more sources to be combined. Hepatitis B, human papillomavirus (HPV) and influenza vaccines (Flublok brand) are made by inserting a segment of the appropriate viral gene into the gene of a yeast cell or virus. The modified yeast cell or virus produces pure hepatitis B surface antigen, HPV capsid protein, or influenza hemagglutinin as it grows. Meningococcal serogroup B vaccines are proteins and outer membrane vesicles created by recombinant technology.

thanks

The editors thank Jennifer Hamborsky, Andrew Kroger, Ginger Redmon, and Skip Wolfe for their contributions to this chapter.

Selected references

American Academy of Pediatrics. Active and passive immunization. In: Kimberlin D, Brady M, Jackson M, et al., eds.Red Book: 2018 Report of the Infectious Diseases Committee. . . . 31. Aufl. Itasca, IL: American Academy of Pediatrics;2018:13–64.

Plotkin S. Correlates of vaccine-induced immunity.Clin Infect Dis2008;47:401–9.

Plotkin S. Vaccines, vaccination and vaccinology.J Infect Dis2003;187:1347–59.

Siegrist C. Vaccine Immunology. In: Plotkin S, Orenstein W, Offit P, et al., Hrsg. Plotkinsvaccinations.7th ed. Elsevier;2018:16-34.