Chapter 12: Bacterial Vaccines

Several bacterial diseases can be prevented by using immunizations that induce either active or passive immunity. Active immunity is induced by vaccines prepared from bacteria or their products. This chapter presents a summary of the types of vaccines (Table 12–1); detailed information regarding each vaccine is located in the chapters on the specific organisms. Passive immunity is provided by the administration of preformed antibody in preparations called immune globulins. The immune globulins useful against bacterial diseases are described later. Passive–active immunity involves giving both immune globulins to provide immediate protection and a vaccine to provide long-term protection. This approach is described later in the section on tetanus antitoxin.

Bacterial vaccines are composed of capsular polysaccharides, inactivated protein exotoxins (toxoids), killed bacteria, or live, attenuated bacteria. The available bacterial vaccines and their indications are described next. Table 12–2 lists the bacterial (and viral) vaccines recommended for children from 0 to 6 years of age as of 2017. Table 12-3 lists some important bacterial (and viral) vaccines recommended for travelers. Location and duration of travel are important factors when determining whether a vaccine should be recommended. Additional information regarding vaccines for travelers can be found at the website for the Centers for Disease Control and Prevention: www.cdc.gov/travel.

Capsular Polysaccharide Vaccines

1. Both versions of the vaccine against Streptococcus pneumoniae contain the capsular polysaccharide of the bacteria as the immunogen. One version contains the capsular polysaccharide of the 23 most prevalent serotypes. It is recommended for persons older than 60 years of age and adult patients of any age with such chronic diseases as diabetes and cirrhosis or with compromised spleen function or splenectomy. A second version containing the capsular polysaccharide of 13 pneumococcal serotypes coupled to a carrier protein (diphtheria toxoid) is available for the protection of young children who do not respond well to the unconjugated vaccine. The function of the carrier protein is explained in Figure 57–3.

   A potential problem regarding the use of the pneumococcal vaccine (or a vaccine against any organism with multiple serotypes) is that of serotype replacement. Will the vaccine reduce the incidence of disease caused by the serotypes in the vaccine but not the overall incidence of disease because other serotypes that are not in the vaccine will now cause disease? In fact, this occurred. An increase in invasive pneumococcal disease caused by serotype 19A, a serotype not in the previous vaccine, was observed. In view of this, serotype 19A is included in the current 13 serotype vaccine.

2. There are more than a dozen serogroups of Neisseria meningitidis that are classified according to the capsular polysaccharide. Serogroups A, B, C, W, and Y are the primary causes of meningococcal disease throughout the world. In the United States, two quadrivalent meningococcal polysaccharide vaccines conjugated to either diphtheria toxoid or tetanus toxoid are available that protect against serogroups A, C, W, and Y. Immunization with conjugate vaccines elicits a much more robust antibody response, particularly in children, than vaccine formulations containing only polysaccharide as the main antigen.

   Until recently, efforts to develop a vaccine against serogroup B strains were unsuccessful because the capsule of that serogroup is composed of a polysaccharide that is also found on the surface of many host tissues. This makes it a poorly immunogenic antigen, and any antibodies raised against the polysaccharide could potentially elicit an autoimmune response by cross-reacting with host cell surfaces. Nonpolysaccharide vaccines against serogroup B were licensed beginning in 2014 (see below).

3. Haemophilus influenzae vaccine contains the type b polysaccharide conjugated to diphtheria toxoid or other carrier protein. It is given to children between the ages of 2 and 15 months to prevent meningitis. The capsular polysaccharide alone is a poor immunogen in young children, but coupling it to a carrier protein greatly enhances its immunogenicity. A combined vaccine consisting of this vaccine plus the diphtheria, tetanus, and pertussis (DTP, DTaP) vaccine is available.

4. One of the vaccines against typhoid fever contains the capsular polysaccharide of Salmonella typhi. It is indicated for persons living or traveling in areas where there is a high risk of typhoid fever and for persons in close contact with either infected patients or chronic carriers.

Toxoid Vaccines

1. Corynebacterium diphtheriae vaccine contains the toxoid (formaldehyde-treated exotoxin). Immunization against diphtheria is indicated for every child and is given in three doses at 2, 4, and 6 months of age, with boosters given 1 year later and at intervals thereafter.

2. Clostridium tetani vaccine contains tetanus toxoid (formaldehyde-treated exotoxin) and is given to everyone both early in life and later as boosters for protection against tetanus.

3. Bordetella pertussis vaccine contains pertussis toxoid but includes other proteins as well. Therefore, it is described in the next section.

Purified Protein Vaccines

1. There are two types of B. pertussis vaccines: an acellular vaccine containing purified proteins and a vaccine containing whole killed bacteria. The acellular vaccine is now recommended in the United States. The principal antigen in the acellular vaccine is inactivated pertussis toxin (pertussis toxoid), but other proteins, such as filamentous hemagglutinin and pertactin, are also required for full protection. Pertussis toxin for the vaccine is inactivated genetically by introducing two amino acid changes that eliminate its toxic (ADP-ribosylating) activity but retain its antigenicity. It is the first vaccine to contain a genetically inactivated toxoid. The vaccine is indicated for every child as a protection against whooping cough. It is usually given in combination with diphtheria and tetanus toxoids (DTP or DTaP vaccine).

2. Bacillus anthracis vaccine contains “protective antigen” purified from the organism. It is given to persons whose occupations place them at risk of exposure to the organism.

3. As mentioned above, challenges developing a polysaccharide-based vaccine for N. meningitidis serogroup B were overcome with the introduction of vaccines containing one or more surface-exposed proteins expressed by N. meningitidis serotype B. Factor H binding protein is main antigen in these vaccines against serogroup B meningococci. These vaccines are discussed in depth in Chapter 16.

Live, Attenuated Bacterial Vaccines

1. The vaccine against tuberculosis contains a live, attenuated strain of Mycobacterium bovis called bacillus Calmette-Guérin (BCG) and, in some countries (but not the United States), is recommended for children at high risk for exposure to active tuberculosis.

2. One of the vaccines against typhoid fever contains live, attenuated S. typhi. It is indicated for persons living or traveling in areas where there is a high risk of typhoid fever and for persons in close contact with either infected patients or chronic carriers.

3. The vaccine against tularemia contains live, attenuated Francisella tularensis organisms and is used primarily in people who are exposed in their occupation, such as laboratory personnel, veterinarians, and hunters.

4. An oral, live attenuated cholera vaccine (Vaxchora) is used in the United States for travelers to areas where cholera caused by serogroup O1 is endemic.

Killed Bacterial Vaccines

1. Another Vibrio cholerae vaccine contains killed organisms. It is not available in the United States but is used in many other countries where cholera is endemic.

2. Yersinia pestis vaccine contains killed organisms and is indicated for persons at high risk for contracting plague.

3. The vaccine against typhus contains killed Rickettsia rickettsiae organisms and is used primarily to immunize members of the armed forces.

4. The vaccine against Q fever contains killed Coxiella burnetii organisms and is used to immunize those who are at high risk for being exposed to animals infected with the organism.

Passive Immunity

Antitoxins (immune globulins) can be used for either the treatment or prevention of certain bacterial diseases. The following preparations are available:

1. Tetanus antitoxin is used in the treatment of tetanus and in its prevention (prophylaxis). In treatment, because the goal is to neutralize any unbound toxin to prevent the disease from getting worse, the antitoxin should be given promptly. In prevention, the antitoxin is given to inadequately immunized persons with contaminated (“dirty”) wounds. The antitoxin is made in humans to avoid hypersensitivity reactions. In addition to the antitoxin, these people should receive tetanus toxoid. This is an example of passive–active immunity. The toxoid and the antitoxin should be given at different sites in the body to prevent the antitoxin from neutralizing the toxoid.

2. Botulinum antitoxin is used in the treatment of botulism. Because the antitoxin can neutralize unbound toxin to prevent the disease from progressing, it should be given promptly. It contains antibodies against botulinum toxins A, B, and E, the most commonly occurring types. The antitoxin is made in horses, so hypersensitivity may be a problem.

3. Diphtheria antitoxin is used in the treatment of diphtheria. The antitoxin can neutralize unbound toxin to prevent the disease from progressing; therefore, the antitoxin should be given promptly. The antitoxin is made in horses, so hypersensitivity may be a problem.

4. Bezlotoxumab, a monoclonal antibody against exotoxin B of Clostridium difficile, is effective in preventing relapses of pseudomembranous colitis.

Waning Immunity to Vaccines

The duration of protection provided by vaccines can decline with time, that is, it can wane. It also varies greatly from one vaccine to another. Evidence that waning immunity is a medical problem is based on the observation that some cases of vaccine-preventable diseases occur in those who have been immunized. For example, in the 2019 outbreak of measles in the United States, about 3% of adults who contracted measles received the MMR (measles, mumps, and rubella) vaccine.

Some vaccines provide adequate protection for months and others for many years. For example, the protection induced by the acellular pertussis vaccine wanes rapidly during the first few years, but the protection induced by the tetanus and diphtheria vaccine lasts for at least a decade.

One suggested explanation for waning immunity is that the ability of memory cells to survive and to retain function declines with time. One explanation offered for this decline is that the response of memory cells may depend upon the precise nature of the antigen used in the vaccine. Determining the criteria required to induce long-lived immunity will be important in developing more effective vaccines.