Chapter 6: Immunoprophylaxis
Learning Objectives
By the end of this chapter you will be able to:
- Explain the role of individual and herd immunity in public immunization programs.
- Distinguish between passive and active immunity as well as natural and artificial immunity.
- Describe the historical basis of vaccines and the different types of modern approaches for immunization.
Case Study
Alex was diagnosed with Common Variable Immunodeficiency (CVID) in their 30s. CVID is a primary immunodeficiency disorder characterized by a variable impairment of the immune system, specifically affecting antibody production. The first indications for Alex’s condition were frequent recurrent infections of the respiratory tract and ears. Blood tests showed hypogammaglobulinemia.
Alex has been hospitalized for infection several times and requires regular antibiotics treatments. Due to the impaired immune response, vaccinations are not effective for Alex. As a consequence, Alex relies on herd immunity, which is a strategy that uses vaccination or previous infections to reduce the overall spread of pathogens within the community.
Immunodiagnostic tests, such as ELISA, are used to monitor Alex’ antibody levels and Alex receives intravenous immunoglobulin (IVIG) therapy in an effort to establish passive immunity and prevent severe infection.
- What do you think caused this immunodeficiency disorder in Alex?
- Why might vaccines not work for Alex and how does herd immunity compensate for this situation?
- How can components of the immune system be used to develop the immunotherapies (e.g. IVIG) that help keep Alex safe?
Answers to these questions are at the end of the chapter.
6.1 Individual and Population Level Immunity
The term immunity is often used to describe the resistance to infection by a particular pathogen or to infectious disease achieved by engaging the adaptive immune response. The adaptive immune response produces memory lymphocytes that can be activated by antigen in a manner independent of antigen presentation. The resulting secondary immune response occurs more quickly, is more intense and may eliminate a pathogen before a person experiences infectious disease. As such, there is a benefit when an otherwise healthy person recovers from infection because they develop immunity to protect themselves when their immune system is more vulnerable.
In addition to immunity in an individual person, the concept of immunity can be extended to entire populations. As more people recover from an infection, there are fewer potential hosts in the population for the pathogen to infect and spread. This creates a phenomenon called herd immunity, where the initial rapid spread of infection ultimately slows down and the pathogen may even be eliminated from the population if there are no suitable hosts to allow it to spread.
Figure 6-1 Herd Immunity. The top image illustrates a scenario where there is no pre-existing immunity. Almost everybody in the population becomes infected, except a few individuals who are perhaps no in contact with other people in the community or are genetically resistant to this particular pathogen. The middle image shows a small fraction of previously immune individuals. These people are individually immune but the pathogen spreads effectively to individuals who did not have prior immunity. The bottom image illustrates herd immunity, where a majority of people are immune from previous exposure. Even those people who are not immune are protected from infection because the pathogen will not spread within this population. [Link to Image Description]
Image Source: By Tkarcher CC BY 4.0, via Wikimedia Commons
Individual Immunity
Immunity provides significant personal protection from specific pathogens. Since immunity operates through prior exposure to pathogens, inducing a person’s immunity could serves as prophylaxis. Prophylaxis is a method of preventative medicine used before the onset of a disease whereas treatment options are used to manage an existing disease condition.
Immunity may be acquired through active or passive mechanisms. Active immunity involves actively triggering a person’s own adaptive immune response. Passive immunity refers to the transfer of adaptive immune components from an individual or animal that is actively immune. These two strategies have distinct benefits and limitations. For example, passive immunization provides an immediate supply of antibodies, which contributes to immediate immune protection that is available to a person whose immune system may be otherwise compromised. However, the supplied antibodies are consumed over time since passive immunization do not generate the memory B-cells needed for longterm immunity. In contrast, active immunization uses a person’s immune system to generate a response. However, the immune protection is delayed by 5-10 days as the adaptive immune system is engaged and may not occur at all if a person is immunocompromised. Active immunity provides longterm protection due to the formation of memory lymphocytes.
Natural and artificial mechanisms to induce active immunity:
Natural Active Immunity – Natural active immunity is developed following an infection. However, in this situation the benefits of exposure should be balanced against the risks of infection. For example, prior to vaccine availability, pox parties were promoted in certain communities, where parents intentionally exposed their children to varicella zoster virus (chickenpox). The belief was that symptoms were more mild in children compared to adults and that infected children would develop longterm immunity. However, chickenpox infection can be fatal even in children and these intentional exposures contributed to the death of 100-150 U.S. children annually.
Artificial Active Immunity – Artificial active immunity involved vaccination. Rather than obtaining immunity by infection with the natural or wild form of a pathogen, individuals are given a “live” vaccine, which incorporates a weakened or “attenuated” version of the pathogen generated in the lab. Live vaccines are effective, but people who are immunocompromised may (albeit rarely) develop an infection from even an attenuated pathogen in a process called reversion. Therefore, live vaccines are not recommended for immunocompromised individuals.
Natural and artificial mechanisms to induce passive immunity:
Natural Passive Immunity – Nature has devised a powerful mechanism to extend a mother’s immunity to protect the newborn baby. Before birth, maternal IgG cross the placenta and accumulate within the circulatory system of the fetus. This placental transfer of antibodies can provide immune protection for six months after birth. After birth, a mother may express breastmilk infused with secretory IgA. These antibodies encase potential pathogens and prevent them from binding and infecting the feeding infant.
Artificial Passive Immunity – Antibodies can be purified from immunized animals (polyclonal antibodies) or may be produced in cell lines within a laboratory (monoclonal antibodies). These purified antibodies may be used as a prophylaxis, prior to pathogen exposure during intravenous immunoglobulin (IVIG) therapies. For example, palivizumab is an antibody that can be offered to children who are at high risk for infection by respiratory syncytial virus (RSV). IVIGs can also be used when a person is exposed to a pathogen if provided within a specific period of time through post-exposure prophylaxis (PEP). When treated with PEP within the window of opportunity antibodies are able to block the infection process. Rabies virus or hepatitis B virus exposures are examples of infections that can be treated with PEP.
Table 6-1. Comparing Passive and Active Immunization
| PASSIVE IMMUNITY |
ACTIVE IMMUNITY |
| Pros: Immediate effect, does not depend on the recipient’s immune status | Pros: Provides longterm immunological memory |
| Cons: No immunological memory | Cons: Response delayed 5-10 days. Immunocompromised persons may have a poor response. |
| Natural: Placental transfer, Breastmilk | Natural: Exposure to pathogen |
| Artificial: Antibodies purified from animals or engineered in laboratory, e.g. “rabies shot” | Artificial: Vaccines consisting of attenuated pathogen, pathogen subunit, pathogen proteins or genetic material coding for those proteins. |
Vaccination
The history behind smallpox variolation and vaccination stands as a testament to humanity’s quest for protection against a deadly disease. Smallpox, caused by the variola virus, is a highly contagious and often fatal disease that afflicted countless individuals throughout history. However, individuals who survive smallpox infections develop robust immunity to future infection.
Variolation is a process believed to have originated from 10th century China where healthy individuals are deliberately inoculated with pustules or scabs from an infected person. While the procedure risked both infection and spread of smallpox, most people treated this way experienced only mild disease.
The advent of modern vaccination is attributed to the groundbreaking work of Dr Edward Jenner, an English physician, in the late 18th century. In 1796, Jenner noticed that milkmaids who contracted cowpox, a related but milder disease, were immune to smallpox. Jenner hypothesized that exposure to cowpox could protect against smallpox. Jenner conducted an experiment in which he deliberately inoculated a young boy with material from cowpox lesions and later exposed him to smallpox. The boy remained unaffected by smallpox, confirming Jenner’s hypothesis. This marked the inception of vaccination, derived from the Latin word “vacca,” meaning cow where antigens from the pathogen are utilized to develop immunological memory.
The vaccine antigen may include a full and competent pathogen or other pathogen components that are immunogenic.
Live Attenuated Vaccines: These vaccines use a weakened form of the live pathogen, which can still reproduce within the host but causes only a mild or asymptomatic infection. Because they closely mimic natural infections, live attenuated vaccines tend to provide strong and long-lasting immunity. Examples include the measles, mumps, and rubella (MMR) vaccine and the oral polio vaccine (OPV). However, live vaccines are generally not suitable for individuals with weakened immune systems.
Inactivated or Killed Vaccines: In these vaccines, the pathogen is rendered non-infectious through physical or chemical processes, such as heat or formaldehyde treatment. Examples include the inactivated polio vaccine (IPV) and the hepatitis A vaccine. While they are safe, inactivated vaccines often require booster shots because they may not induce as long-lasting immunity as live vaccines.
Subunit or Recombinant Vaccines: These vaccines contain only specific proteins or protein subunits from the pathogen, rather than the entire microorganism. Subunit vaccines can be biochemically extracted from the pathogen surface and purified. Recombinant vaccines are produced by engineering pathogen genetic material into other organisms like baker’s yeast or certain plants. The engineered pathogen proteins are purified to generate the vaccine antigen. Subunit and recombinant vaccines are safer than live vaccines but may require adjuvants (substances that enhance the immune response) to be effective. Examples include the hepatitis B vaccine and the human papilloma virus (HPV) vaccine.
Nucleic Acid Vaccines: These are a newer class of vaccines that use only the genetic material from the pathogen, such as DNA or RNA, to induce an immune response. They do not contain live or inactivated pathogens and are considered safe. COVID-19 mRNA vaccines, like the Pfizer-BioNTech and Moderna vaccines, are examples of nucleic acid vaccines.
Virus-Like Particle (VLP) Vaccines: VLP vaccines are designed to mimic the structure of a virus without containing its genetic material. They are made from self-assembled proteins and can stimulate a strong immune response. The human papilloma virus (HPV) vaccine and some experimental vaccines for other viruses utilize VLP technology.
Toxoid Vaccines: These vaccines use toxins produced by certain bacteria rather than the microbe themselves. Toxins are chemically inactivated to create toxoids, which are used as antigens. The tetanus and diphtheria vaccines are examples of toxoid vaccines.
Conjugate Vaccines: Conjugate vaccines combine a weak antigen from the pathogen with a strong antigen from another source (often a protein carrier). This approach is used to enhance the immune response, especially in young children whose immune systems may not respond well to certain antigens. The Haemophilus influenzae type b (Hib) vaccine and certain pneumococcal vaccines are conjugate vaccines.
Table 6-2. A comparison of vaccine types
| Vaccine Type |
PROS | CONS |
| Live Attenuated Pathogen |
Similar to natural infection and produces a strong immune response.
Booster vaccines may not be necessary.
|
Possibility of reversion to a harmful form of pathogen in people who are immunocompromised.
Serological blood tests cannot determine if the immune response is to the vaccine or the ‘wild’ pathogen. |
| Inactivated Pathogen |
No live pathogen used in the vaccine product, making it safer. | Since vaccine pathogen does not replicate, additional vaccine immunizations may be needed to serve as boosters.
Serological blood tests cannot determine if the immune response is to the vaccine or the ‘wild’ pathogen. |
| Purified pathogen subunit or recombinant protein | Only a segment of the pathogen is used, making these vaccines safer than live pathogen.
Recombinant vaccines are inexpensive to mass produce. Since only part of the pathogen is used, serological blood tests can scan the antibodies produced and determine if the immune response is against the vaccine or ‘wild’ pathogen. |
Since the number of antigen is low, immune stimulator chemicals (“adjuvants”) as well as booster shots may be needed.
There are fewer epitopes being engaged in the immune response, compared to inactivated pathogen. The pathogen may evolve and adapt resistance against the antibodies produced by the vaccine. |
| Nucleic Acid Vaccines |
All of the advantages of a recombinant vaccine but even less expensive to produce. | All of the disadvantages of recombinant vaccine. |
Summary
- Herd immunity involves immunizing most individuals in a population in order to protect those individuals who cannot be immunized.
- For an individual, immunization by vaccine can provide a prophylaxis that is given before exposure to pathogen to minimize the impact of an infectious disease.
- Immunization can be natural (infection, breastfeeding) or artificial (immunoglobulin therapy, vaccine).
- Immunization can be passive (provide antibodies, no immunity; e.g. breastfeeding, immunoglobulin therapy) or active (generate immune response to antigen; e.g. infection, vaccine).
- Different types of vaccines are available with different benefits and limitations
