23.8: Classes of Vaccines
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Learning Objectives
- Describe different types of vaccines
- Explain their respective advantages and disadvantages
- Identify the risk associated with a live attenuated vaccine
Classes of Vaccines
For a vaccine to provide protection against a disease, it must expose an individual to pathogen-specific antigens that will stimulate a protective adaptive immune response. By its very nature, this entails some risk. As with any pharmaceutical drug, vaccines have the potential to cause adverse effects. However, the ideal vaccine causes no severe adverse effects and poses no risk of contracting the disease that it is intended to prevent. Various types of vaccines have been developed with these goals in mind. These different classes of vaccines are described in the next section and summarized in Table \(\PageIndex{1}\).
Live Attenuated Vaccines
Live attenuated vaccines expose an individual to a weakened strain of a pathogen with the goal of establishing a subclinical infection that will activate the adaptive immune defenses. Pathogens are attenuated to decrease their virulence using methods such as genetic manipulation (to eliminate key virulence factors) or long-term culturing in an unnatural host or environment (to promote mutations and decrease virulence).
By establishing an active infection, live attenuated vaccines stimulate a more comprehensive immune response than some other types of vaccines. Live attenuated vaccines activate both cellular and humoral immunity and stimulate the development of memory for long-lasting immunity. In some cases, vaccination of one individual with a live attenuated pathogen can even lead to natural transmission of the attenuated pathogen to other individuals. This can cause the other individuals to also develop an active, subclinical infection that activates their adaptive immune defenses.
Disadvantages associated with live attenuated vaccines include the challenges associated with long-term storage and transport as well as the potential for a patient to develop signs and symptoms of disease during the active infection (particularly in immunocompromised patients). There is also a risk of the attenuated pathogen reverting back to full virulence. Table \(\PageIndex{1}\) lists examples of live attenuated vaccines.
Inactivated Vaccines
Inactivated vaccines contain whole pathogens that have been killed or inactivated with heat, chemicals, or radiation. For inactivated vaccines to be effective, the inactivation process must not affect the structure of key antigens on the pathogen.
Because the pathogen is killed or inactive, inactivated vaccines do not produce an active infection, and the resulting immune response is weaker and less comprehensive than that provoked by a live attenuated vaccine. Typically the response involves only humoral immunity, and the pathogen cannot be transmitted to other individuals. In addition, inactivated vaccines usually require higher doses and multiple boosters, possibly causing inflammatory reactions at the site of injection.
Despite these disadvantages, inactivated vaccines do have the advantages of long-term storage stability and ease of transport. Also, there is no risk of causing severe active infections. However, inactivated vaccines are not without their side effects. Table \(\PageIndex{1}\) lists examples of inactivated vaccines.
Subunit Vaccines
Whereas live attenuated and inactive vaccines expose an individual to a weakened or dead pathogen, subunit vaccines only expose the patient to the key antigens of a pathogen—not whole cells or viruses. Subunit vaccines can be produced either by chemically degrading a pathogen and isolating its key antigens or by producing the antigens through genetic engineering. Because these vaccines contain only the essential antigens of a pathogen, the risk of side effects is relatively low. Table \(\PageIndex{1}\) lists examples of subunit vaccines.
Toxoid Vaccines
Like subunit vaccines, toxoid vaccines do not introduce a whole pathogen to the patient; they contain inactivated bacterial toxins, called toxoids. Toxoid vaccines are used to prevent diseases in which bacterial toxins play an important role in pathogenesis. These vaccines activate humoral immunity that neutralizes the toxins. Table \(\PageIndex{1}\) lists examples of toxoid vaccines.
Conjugate Vaccines
A conjugate vaccine is a type of subunit vaccine that consists of a protein conjugated to a capsule polysaccharide. Conjugate vaccines have been developed to enhance the efficacy of subunit vaccines against pathogens that have protective polysaccharide capsules that help them evade phagocytosis, causing invasive infections that can lead to meningitis and other serious conditions. The subunit vaccines against these pathogens introduce T-independent capsular polysaccharide antigens that result in the production of antibodies that can opsonize the capsule and thus combat the infection; however, children under the age of two years do not respond effectively to these vaccines. Children do respond effectively when vaccinated with the conjugate vaccine, in which a protein with T-dependent antigens is conjugated to the capsule polysaccharide. The conjugated protein-polysaccharide antigen stimulates production of antibodies against both the protein and the capsule polysaccharide. Table \(\PageIndex{1}\) lists examples of conjugate vaccines.
| Class | Description | Advantages | Disadvantages | Examples |
|---|---|---|---|---|
| Live attenuated | Weakened strain of whole pathogen | Cellular and humoral immunity | Difficult to store and transport | Chickenpox, German measles, measles, mumps, tuberculosis, typhoid fever, yellow fever |
| Long-lasting immunity | Risk of infection in immunocompromised patients | |||
| Transmission to contacts | Risk of reversion | |||
| Inactivated | Whole pathogen killed or inactivated with heat, chemicals, or radiation | Ease of storage and transport | Weaker immunity (humoral only) | Cholera, hepatitis A, influenza, plague, rabies |
| No risk of severe active infection | Higher doses and more boosters required | |||
| Subunit | Immunogenic antigens | Lower risk of side effects | Limited longevity | Anthrax, hepatitis B, influenza, meningitis, papillomavirus, pneumococcal pneumonia, whooping cough |
| Multiple doses required | ||||
| No protection against antigenic variation | ||||
| Toxoid | Inactivated bacterial toxin | Humoral immunity to neutralize toxin | Does not prevent infection | Botulism, diphtheria, pertussis, tetanus |
| Conjugate | Capsule polysaccharide conjugated to protein | T-dependent response to capsule | Costly to produce |
Meningitis ( Haemophilus influenzae , Streptococcus pneumoniae , Neisseria meningitides ) |
| No protection against antigenic variation | ||||
| Better response in young children | May interfere with other vaccines |
DNA Vaccines
DNA vaccines represent a relatively new and promising approach to vaccination. A DNA vaccine is produced by incorporating genes for antigens into a recombinant plasmid vaccine. Introduction of the DNA vaccine into a patient leads to uptake of the recombinant plasmid by some of the patient’s cells, followed by transcription and translation of antigens and presentation of these antigens with MHC I to activate adaptive immunity. This results in the stimulation of both humoral and cellular immunity without the risk of active disease associated with live attenuated vaccines.
Although most DNA vaccines for humans are still in development, it is likely that they will become more prevalent in the near future as researchers are working on engineering DNA vaccines that will activate adaptive immunity against several different pathogens at once. First-generation DNA vaccines tested in the 1990s looked promising in animal models but were disappointing when tested in human subjects. Poor cellular uptake of the DNA plasmids was one of the major problems impacting their efficacy. Trials of second-generation DNA vaccines have been more promising thanks to new techniques for enhancing cellular uptake and optimizing antigens. DNA vaccines for various cancers and viral pathogens such as HIV, HPV, and hepatitis B and C are currently in development.
Some DNA vaccines are already in use. In 2005, a DNA vaccine against West Nile virus was approved for use in horses in the United States. Canada has also approved a DNA vaccine to protect fish from infectious hematopoietic necrosis virus. 4 A DNA vaccine against Japanese encephalitis virus was approved for use in humans in 2010 in Australia.
Query \(\PageIndex{1}\)
Key Concepts and Summary
- Live attenuated vaccines and inactivated vaccines contain whole pathogens that are weak, killed, or inactivated. Subunit vaccines, toxoid vaccines, and conjugate vaccines contain acellular components with antigens that stimulate an immune response.
Footnotes
- S.B. Halstead and S. J. Thomas. “New Japanese Encephalitis Vaccines: Alternatives to Production in Mouse Brain.” Expert Review of Vaccines 10 no. 3 (2011): 355–64.