by H. Cody Meissner, M.D., FAAP
Vaccine-mediated immunity is surprisingly complex. Vaccines stimulate specific antibodies, but
protection depends not only on the amount of vaccine-induced antibody but also the quality of the
antibody response (antigen binding avidity).
In time, B cells undergo a process whereby mutations result in antibodies that bind to specific bacterial and viral antigens with greater avidity (called
affinity maturation). The B cell response to a vaccine
antigen is mediated by T cells that are important for
long-term immunologic memory.
Match each of the following vaccines to
the best category:
BCG vaccine is a live bacterial vaccine. It generally
is not recommended for use in the United States
because of the low risk of infection with
Mycobacterium tuberculosis, variable BCG effectiveness against
tuberculosis and the vaccine’s ability to interfere with
tuberculin skin test reactivity (but not current interferon gamma release assays). BCG sometimes is
used in U.S. children who have a negative skin test,
will have long-term exposure to adults who are not
treated effectively for tuberculosis or have isolates
resistant to isoniazid and rifampin.
Encapsulated H. influenzae have a polysaccharide capsule that is one of several virulence factors.
The polysaccharide capsule enables the organism
to evade the mucosal immune response by resist-
ing bactericidal antibody and opsonic activity and
by protecting the organism from phagocytosis and
complement mediated lysis. The polysaccharide cap-
sule of type b appears to be particularly effective at
avoiding complement mediated killing and splenic
clearance. Other virulence factors (not contained
in the vaccine) include lipooligosaccharides that are
toxic to epithelial cells of the upper respiratory tract,
facilitating passage through the nasopharyngeal mu-
Two rabies vaccines are available in the United
States. One is grown in human diploid cells (Imovax,
Sanofi Pasteur), and one is grown in chick embryo
cells (RabAvert, Novartis). β-propiolactone is used
for inactivation of both vaccines. The two vaccines
are considered equally safe and effective. Treatment
after an exposure to a possibly rabid animal in a
previously unvaccinated person requires a dose of
rabies immune globulin and four (or five if the person’s immune system is suppressed) doses of vaccine.
Vaccination before exposure requires three doses of
vaccine and no immune globulin.
Currently recommended influenza vaccines consist primarily of surface proteins, hemagglutinin
and neuraminidase. For practical purposes, the duration of immunity following inactivated influenza
vaccination is less than one year because of waning of vaccine-induced antibody. Influenza vaccine
effectiveness varies by the similarity of the vaccine
strain(s) to the circulating strain(s) and the recipient’s age and health status. During the 2016-’ 17
season, the adjusted overall vaccine effectiveness
against medically attended events is estimated to be
48%. Because the recommended influenza vaccines
are killed vaccines, there is no risk of acquiring influenza from the vaccine.
Diphtheria vaccine consists of diphtheria toxoid.
A toxoid is a bacterial toxin that has been rendered
harmless but still elicits a protective immune response against the toxin. Diphtheria toxoid is produced by growing toxigenic C. diphtheriae in liquid
medium. The filtrate is incubated with formaldehyde to convert toxin to toxoid and then is adsorbed
onto an aluminum salt.
Hepatitis B vaccines are recombinant vaccines.
The two vaccines are produced by inserting a plasmid
containing the gene for hepatitis B surface antigen
(HBsAg) into common baker’s yeast (Saccharomyces
cerevisiae). During a fermentation pro-
cess, growth of Saccharomyces cerevisiae
produces the surface protein, HBsAg,
which is harvested and purified. The
recombinant vaccine contains more
than 95% HBsAg protein, but no
yeast DNA is detectable in the vaccine.
HBV infection cannot result from use
of the recombinant vaccine, since no
potentially infectious viral DNA or
complete viral particles are produced
in the recombinant system.
Measles virus was first isolated by
John Enders in 1954. Both an inactivated and a live attenuated vaccine
The only measles virus vaccine currently available in the United States is a live, more attenuated
Edmonston-Enders strain. The vaccine is available
as a combination vaccine with mumps and rubella
vaccines (MMR) or as a combination vaccine with
mumps, rubella and varicella vaccine (MMRV).
Single-antigen measles vaccine is not available in
the United States.
Dr. Meissner is professor of pediatrics
at Floating Hospital for Children, Tufts
Medical Center. He also is an ex officio
member of the AAP Committee on Infectious Diseases and associate editor of
the AAP Visual Red Book.
AAP Red Book chapter on vaccine ingredients, http://
Answers:a) 3,b) 4,c) 2,d) 6,e) 5,f) 7,g) 1
Vaccines protect against disease in remarkably diverse ways
This month in Pediatrics
Coming in the August issue of Pediatrics:
• Guiding Principles for Team-Based Pediatric Care
• Quality Early Education and Child Care From
Birth to Kindergarten
• Oral and Dental Aspects of Child Abuse and
• The Metabolic Syndrome in Children and Ado-
lescents: Shifting the Focus to Cardiometabolic
• Operating Procedures for Pediatric Telehealth
a)Bacille Calmette-Guérin (BCG)
b) Haemophilus influenzae type b
f) Hepatitis B
1. Live attenuated virus
2. Inactivated virus
3. Live attenuated
4. Bacterial polysaccharide
5. Inactivated protein
6. Surface proteins
7. Genetically engineered vaccine