Principles of Vaccination

1

1 Immunology and Vaccine-Preventable Diseases

To understand how vaccines work and the foundation of 

recommendations for 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 ability of the human body to tolerate the 

presence of material indigenous to the body and to eliminate 

foreign substances. This discriminatory ability to eliminate 

foreign substances is performed by a complex system of 

interacting cells called the immune system. Since most 

organisms (e.g., bacteria, viruses, and fungi) are identified as 

foreign, the ability to identify and eliminate these substances 

provides protection from infectious diseases. Immunity is 

generally specific to a single organism or 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 major component of humoral immunity) by

B-lymphocytes (B-cells)

• Specific cells, including T-lymphocytes (also known

as cell-mediated immunity)

The most effective immune responses are generally produced 

in response to antigens present in a live organism. However, 

an antigen does not necessarily have to be present in a live 

organism to produce an immune response. Some antigens, 

such as hepatitis B surface antigen, are easily recognized by 

the immune system and produce adequate protection even 

if they are not carried on the live hepatitis B virus. Other 

materials are less effective antigens, and the immune response 

they produce may not provide good protection. 

A. Patricia Wodi, MD and Valerie Morelli, BA

NOTES

https://www.cdc.gov/vaccines/pubs/pinkbook/prinvac.html Aug 2021
2

Principles of Vaccination

 1 Types of Immunity

There are two basic mechanisms for acquiring immunity: 

passive and active. 

Passive Immunity

Passive immunity is protection by antibody or antitoxin 

produced by one animal or human and transferred to another. 

Passive immunity provides immediate protection against 

infection, but that protection is temporary. The antibodies will 

degrade during a period of weeks to months, and the recipient 

will no longer be protected. 

The most common form of passive immunity is that which an 

infant receives from the mother. Antibodies, specifically the 

class of antibody referred to as IgG, are transported across the 

placenta, primarily during the last 1 to 2 months of pregnancy. 

As a result, a full-term infant will have the same type of 

antibodies as the mother. These antibodies can protect the 

infant from certain diseases within the first few months after 

birth. Maternal antibodies provide better protection from some 

diseases (e.g., measles, rubella, tetanus) than from others (e.g., 

polio, pertussis).

Passive immunity can also be acquired through the transfusion 

of blood products. Some blood products (e.g., washed or 

reconstituted red blood cells) contain a relatively small amount 

of antibody, while some (e.g., intravenous immune globulin and 

plasma products) contain a large amount. 

In addition to blood products used for transfusion, there are 

three other major sources of antibody 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 immune 

globulin, is produced by combining the antibody fraction, 

specifically the class of antibody referred to as IgG, from the 

blood of thousands of adult donors. Because it comes from 

many different donors, it contains antibody to many 

different antigens. It is used primarily for prophylaxis for 

hepatitis A and measles, and treatment of certain congenital 

immunoglobulin deficiencies. 

NOTES
Principles of Vaccination

3

1

Homologous human hyperimmune globulins are antibody 

products that contain high titers of antibody targeting more 

specific antigens. These products are made from donated 

human plasma with high levels of the antibody of interest. Since 

hyperimmune globulins are from humans, they are primarily 

polyclonal, containing many types of antibodies in lesser 

quantities. Hyperimmune globulins are used for postexposure 

prophylaxis for several diseases, including hepatitis B, rabies, 

tetanus, and varicella. 

Heterologous hyperimmune serum, also known as antitoxin, is 

produced in animals, usually horses, and contains antibodies 

against only one antigen. In the United States, antitoxins are 

available for the treatment of botulism and diphtheria. These 

products can cause serum sickness, an immune reaction to the 

horse protein. 

Immune globulin products from human sources are primarily 

polyclonal; they contain many kinds of antibodies. Monoclonal 

antibody products have many applications, including the 

diagnosis of certain types of cancer (colorectal, prostate, 

ovarian, breast), treatment of cancer (B-cell chronic lymphocytic 

leukemia, non-Hodgkin lymphoma), prevention of transplant 

rejection, and treatment of autoimmune (Crohn’s disease, 

rheumatoid arthritis) and infectious diseases. 

While certain antibody products, such as immune globulins, 

interfere with the immune response to live-virus vaccines, 

monoclonal antibody products do not because they are 

directed against one antigen or a closely related group of 

antigens. A monoclonal antibody product, palivizumab 

(Synagis), is available for the prevention of respiratory syncytial 

virus (RSV) infection. Since Synagis only contains RSV antibody, 

it will not interfere with the response to a live vaccine.

Active Immunity

Active immunity is protection produced 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 a lifetime. 

One way to acquire active immunity is to survive infection with 

the disease-causing form of the organism. In general, once 

persons recover from infectious diseases, they will have lifelong 

immunity to that disease (there are exceptions, e.g., malaria). 

The persistence of protection for many years after the infection 

is known as immunologic memory. Following exposure of the 

immune system to an antigen, certain memory B-cells continue 

to circulate in the blood and reside in the bone marrow for 

many years. Upon re-exposure to the antigen, these memory 

NOTES
4

Principles of Vaccination

 1

cells begin to replicate and produce antibody rapidly to 

reestablish protection. 

Another way to produce active immunity is by vaccination. 

Vaccines contain antigens that stimulate the immune 

system to produce an immune response that is often similar 

to that produced by the natural infection. With vaccination, 

however, the recipient is not subjected to the disease and its 

potential complications. 

Many factors may influence the immune response to 

vaccination. These include the presence of maternal antibody, 

the nature and dose of antigen, the route of administration, 

and the presence of an adjuvant (e.g., aluminum-containing 

material added to improve immunogenicity of the vaccine). 

Host factors, such as age, nutrition, genetics, and coexisting 

disease, may 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. Their characteristics 

are different and determine how each type is used.

1. Live, attenuated, and 

2. Inactivated. 

Live, Attenuated Vaccines

Live vaccines are derived from “wild” viruses or bacteria. 

These wild viruses or bacteria are attenuated (weakened) in 

a laboratory, usually by repeated culturing. For example, the 

measles virus used as a vaccine today was isolated from a child 

with measles disease in 1954. Almost 10 years of serial passage 

using tissue culture media were required to transform the wild 

virus into the attenuated vaccine virus.

To produce an immune response, live, attenuated vaccines must 

replicate in the vaccinated person. A relatively small dose of 

administered virus or bacteria replicates in the body and creates 

enough of the organism to stimulate an immune response. 

Although live, attenuated vaccines replicate, they usually do 

not cause disease such as that caused by the wild form of the 

organism. When a live, attenuated vaccine does cause 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 produced by a natural infection because the 

immune system does not differentiate between an infection 

with a weakened vaccine virus and an infection with a wild 

NOTES
Principles of Vaccination

5

1

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 provide 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 may cause severe or fatal infections 

as a result of uncontrolled replication of the vaccine virus or 

bacteria. However, this only occurs in persons with a weakened 

immune system (e.g., from 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 happen only with 

live (oral) polio vaccine, which is no longer available in the 

United States. 

Active immunity from a live, attenuated vaccine may not 

develop because of interference with the vaccine virus 

by circulating antibody. Antibody from any source (e.g., 

transplacental transfer to infants, transfusion of blood products) 

can interfere with replication of the vaccine organism and lead 

to poor response 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 carefully. The live, attenuated viral vaccines currently 

available and routinely recommended in the United States 

are MMR, varicella, rotavirus, and influenza (intranasal). Other 

non-routinely recommended live vaccines include adenovirus 

vaccine (used by the military), typhoid vaccine (Ty21a), and 

Bacille Calmette-Guerin (BCG). BCG is not used as a vaccine in 

the United States, but as a treatment for bladder cancer.

Inactivated Vaccines

Inactivated vaccines are not live and cannot replicate. These 

vaccines cannot cause disease, even in an immunodeficient 

person. Inactivated antigens are less affected by circulating 

antibody than are live antigens, so they may be given when 

antibody is present in the blood (e.g., in infancy or following 

receipt of antibody-containing blood products).

The immunity provided by inactivated vaccines is generally not 

as long-lasting as that obtained from live, attenuated vaccines. 

Multiple doses over time are needed to obtain ongoing 

immunity. In general, the first dose does not produce protective 

immunity, but “primes” the immune system. A protective 

NOTES
6

Principles of Vaccination

 1

immune response develops after the second or third dose. 

Unlike live vaccines, which produce an immune response that 

closely resembles natural infection, the immune response to 

an inactivated vaccine is mostly antibody production. Little or 

no cellular immunity results. Antibody titers against inactivated 

antigens diminish with time. As a result, some inactivated 

vaccines may require periodic supplemental doses to increase, 

or “boost,” antibody titers. 

Inactivated vaccines include whole-cell inactivated vaccines 

(e.g., polio, hepatitis A, and rabies vaccines), subunit vaccines 

(e.g., influenza and pneumococcal vaccines), toxoids (e.g., 

diphtheria and tetanus toxoid), and recombinant vaccines 

(e.g., hepatitis B, human papillomavirus [HPV], and influenza 

[Flublok brand]). 

Whole-cell inactivated vaccines contain bacteria or viruses 

that have been killed through a physical or chemical process. 

Whole-cell inactivated viral vaccines against polio, hepatitis A, 

and rabies are available in the United States. A vaccine made 

from whole killed pertussis (whooping cough) bacteria is 

available outside the United States.

Subunit vaccines contain a portion of the bacteria or virus. The 

portion of the organism selected is the part needed to produce 

a protective immune response. Antigens in subunit vaccines can 

be protein, polysaccharide, or a combination of polysaccharide 

and protein molecule (i.e., conjugate vaccine).

Conjugate subunit vaccines (e.g., Haemophilus influenzae 

type b and pneumococcal conjugate vaccines) are produced 

by chemically attaching a polysaccharide from the surface 

of bacteria to a protein molecule through a process called 

conjugation. Conjugating a polysaccharide antigen to a protein 

molecule produces long-lasting protective immunity to the 

polysaccharide antigen. 

The immune response to a pure polysaccharide vaccine is 

typically T-cell-independent, which means these vaccines 

can stimulate B-cells without the assistance of T-helper cells. 

T-cell-independent antigens, including polysaccharide vaccines, 

are not consistently immunogenic in children younger than 

age 2 years, probably because of immaturity of the immune 

system. Attaching the polysaccharide antigen to a protein 

makes it possible to prevent bacterial infections in populations 

where a polysaccharide vaccine is not effective or provides only 

temporary protection.

NOTES
Principles of Vaccination

7

1

Toxoid vaccines are made using inactivated toxins produced 

by bacteria. These protein-based toxins are inactivated using 

heat, chemicals, or other methods. Some bacteria (e.g., tetanus, 

diphtheria) cause disease by producing toxins. The ability of 

the immune system to recognize and eliminate these toxins 

provides protection from the disease.

Recombinant vaccines are produced by recombinant DNA 

technology. Recombinant DNA technology enables the 

combination of DNA from two or more sources. Hepatitis B, 

human papillomavirus (HPV), and influenza (Flublok brand) 

vaccines are produced by insertion of a segment of the 

respective 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 when 

it grows. Serogroup B meningococcal vaccines are proteins and 

outer membrane vesicles generated by recombinant technology.

Acknowledgements

The editors would like to acknowledge 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 Committee on Infectious Diseases. 

31st ed. Itasca, IL: American Academy of Pediatrics;2018:13–64.

Plotkin S. Correlates of vaccine-induced immunity. 

Clin Infect Dis 2008;47:401–9. 

Plotkin S. Vaccines, vaccination, and vaccinology.

J Infect Dis 2003;187:1347–59.

Siegrist C. Vaccine immunology. In: Plotkin S, Orenstein W, Offit 

P, et al., eds. Plotkin’s Vaccines. 7th ed. Elsevier;2018:16–34.

NOTES
8

Principles of Vaccination

 1 NOTES