PUBH501, Fall 2015 : Topics in

Community & Preventive

Medicine

Vaccines and
Vaccine-Preventable Diseases

Learning Objectives
Distinguish active from passive immunity
Describe different types of vaccines (e.g., live
attenuated vs. inactivated vs. toxoid)
List the vaccines currently recommended for
children, adolescents, adults, and healthcare
workers
Note: you will not be tested on the clinical
features of the diseases discussed today
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CPM Vaccines, VPDs

Prophylaxis, Chemoprophylaxis
Prophylaxis any medical or public health
procedure whose purpose is to prevent rather
than treat or cure a disease
Chemoprophylaxis administration of a
medication for the purpose of preventing disease
or infection
Examples

Antimalarial drugs
Antibiotics prior to surgery
Aspirin
Vaccines

CPM Vaccines, VPDs

History
1796 Edward Jenner
inoculated 8-year old James
Phipps with cowpox pus;
protected against smallpox
Smallpox caused by Variola
Cowpox caused by Vaccinia
(Latin: vacca = cow)

CPM Vaccines, VPDs

Year of Vaccine Development (17981927)

or Licensure in U.S. (1945present)
Disease
Smallpox
Rabies
Typhoid fever
Cholera
Plague
Diphtheria
Pertussis
Tetanus
Tuberculosis
Influenza
Yellow fever
Poliomyelitis
Measles
Mumps

Year
1798
1885
1896
1896
1897
1923
1926
1927
1927
1945
1953
1955
1963
1967

Disease
Rubella
Anthrax
Meningitis
Pneumococcal pneumonia
Adenovirus
Hepatitis B
Haemophilus
influenzae type B
Japanese encephalitis
Hepatitis A
Varicella
Lyme Disease
Rotavirus
Human papilloma

Year
1969
1970
1975
1977
1980
1981
1985
1992
1995
1995
1998
1998
2006
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CPM Vaccines, VPDs

Number of Annual Cases, United States

Annual Cases
Disease
Pre-vaccine era
Smallpox
48,164
Diphtheria
175,865
Pertussis
147,271
Tetanus
1,314
Polio, paralytic
16,316
Measles
503,282
Mumps
152,209
Rubella
47,745
Congenital rubella
823 est.
H. flu <5 years
20,000 est.

Years
19001904
19201922
19221925
19221926
19511954
19581962
1968
19661968
19661968
1985
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CPM Vaccines, VPDs

Smallpox
Variola major (more common)
and minor forms
Mostly droplet spread
incubation period ~ 12-14
days, then 2-4 day prodrome,
then rash begins
Rash becoming blisters, all
same stage
~ 30% case-fatality rate for
variola major
Only communicable disease
eradicated by human efforts
CPM Vaccines, VPDs

Other Vaccine-Preventable Rash Illnesses

Chickenpox /
Varicella

Rubella /
German Measles

Measles
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CPM Vaccines, VPDs

Other Vaccine-Preventable
Childhood Illnesses
Pertussis /
Whooping Cough

Mumps

Diphtheria
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CPM Vaccines, VPDs

Vaccine-Preventable Neuromuscular Diseases

Tetanus

Poliomyelitis
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CPM Vaccines, VPDs

Terms
Vaccine any biologically derived substance
that elicits a protective immune response when
administered to a suspectible host
Vaccination* administration of a vaccine
Immunization* development of immunity
after vaccination
* often used interchangeably
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CPM Vaccines, VPDs

More Terms
Antigen
substance that, when introduced into the body,
stimulates immune response such as production
of antibody. Examples: toxins, microorganisms,
foreign blood cells, cells of transplanted organs
Antibody (Immunoglobulin)
protein produced by B lymphocytes in response
to antigenic stimulus that neutralizes the antigen
by binding to it
purpose is to facilitate elimination / destruction
of the foreign substance
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CPM Vaccines, VPDs

Key Concept: Immunologic Memory

Following exposure to an antigen, specific
memory B cells circulate in blood (and reside
in bone marrow) for many years
Upon re-exposure to the antigen, these B cells
replicate and produce antibody to neutralize
the threat

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CPM Vaccines, VPDs

Active vs. Passive Immunity

Passive Immunity
Protection conferred to a susceptible host by
transfer of immunity products from another
person or animal
Temporary protection that wanes with time
Examples:

Maternal antibodies across placenta or in milk

Immune globulin
Hyperimmune globulin
Antitoxins
Antivenoms
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CPM Vaccines, VPDs

Active vs. Passive Immunity

Active Immunity
Protection produced by the person's own
immune system (in response to nonself
antigen)
Usually long-lasting (permanent)
Basic premise of immunization:
Immunity and immunologic memory similar to
natural infection but without the disease

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CPM Vaccines, VPDs

Classification of Vaccines
Traditional
Live attenuated
Inactivated

New types
Recombinant
Naked DNA

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CPM Vaccines, VPDs

Live Attenuated Vaccines

Vaccine in which live wild virus is weakened
(attenuated) through chemical or physical
processes in order to process an immune
response without causing clinical disease
Must replicate in the host to be effective
Immune response similar to natural infection, and
stronger than inactivated vaccines
Induce both humoral and cell-mediated immunity
Usually requires fewer doses*
*except those administered orally
CPM Vaccines, VPDs

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Edmonston B Measles Vaccine

Wild type
virus, 1954

24 passages in human kidney tissue

28 passages in Io human amnion tissue

6 passages in
chick embryos

Chick embryo
cells

Edmonston B
vaccine, 1963

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CPM Vaccines, VPDs

Live Attenuated Vaccines

Fragile must be stored and handled carefully (for
most, need to maintain cold chain)
Severe reactions possible, particularly in
immunocompromised individuals
Interference from circulating antibody (e.g.,
measles vaccine and maternal antibodies)
Rarely, can convert back to virulent strain (e.g.,
OPV-associated polio, Dominican Republic, 2000)
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CPM Vaccines, VPDs

Live Attenuated Vaccines

Viral

Bacterial

influenza (intranasal)
measles
mumps
polio (oral)*
rubella
rotavirus
vaccinia
varicella/zoster
yellow fever

BCG
typhoid (oral)

*not available in the United States

CPM Vaccines, VPDs

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Inactivated Vaccines
Inactivated by heat or chemicals
Cannot replicate or revert
Generally not as effective as live vaccines
Less interference from circulating antibody than
live vaccines
Fewer side effects (usually localized, if any)
Generally require 3-5 doses
Immune response mostly humoral
Antibody titer may diminish with time, requiring
boosters
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CPM Vaccines, VPDs

Inactivated Vaccines
Whole
viruses
bacterial

Fractional
protein-based
toxoid (inactivated toxin)
subunit
polysaccharide-based
pure
conjugate

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CPM Vaccines, VPDs

Inactivated Vaccines
Viral, whole-cell

hepatitis A
japanese encephalitis
polio
rabies

Viral, fractional
hepatitis B
influenza
human papillomavirus

*not available in the United States

CPM Vaccines, VPDs

Bacterial, whole-cell

cholera*
pertussis*
plague*
typhoid*

Bacterial, fractional
anthrax
acellular pertussis

Bacterial, toxoid
diphtheria
tetanus
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Poliomyelitis Vaccines
Inactivated polio vaccine (IPV)

Developed by Jonas Salk

Licensed in 1955
Given by intramuscular injection
Can be used for immuncompromised persons

Live attenuated oral polio vaccine (OPV)

Developed by Albert Sabin

Licensed in 1963
Given orally
Attenuated virus shed in stool
Provides longer lasting immunity than IPV

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CPM Vaccines, VPDs

Even More Vaccine Terms

Combination vaccine combination of two or
more vaccines (e.g., diphtheria/tetanus/pertussis)
Conjugate vaccine vaccine in which a
polysaccharide antigen is chemically joined with a
protein molecule to improve the immunogenicity of
the polysaccharide
Adjuvant substance that is used in a vaccine to
improve the immune response so that less vaccine
is needed to produce a non-specific stimulator of
the immune response
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CPM Vaccines, VPDs

Polysaccharide Vaccines
Not consistently immunogenic in children < 2
years of age
No booster response
Antibody with less functional activity
Immunogenicity improved by conjugation to a
protein
Pure polysaccharide
meningococcal
pneumococcal
Salmonella Typhi

Conjugate
meningococcal
pneumococcal
H. influenzae type B
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CPM Vaccines, VPDs

Recombinant Vaccines
Genetic manipulation of organisms to generate
either live attenuated or inactivated vaccines
Insert antigen-producing gene into yeast cell to produce large
quantities of antigen (hepatitis B capsular, HPV capsid)
Delete or modify pathogenicity (rotavirus)
insert gene into another acts as transport (rabies protein into
adenovirus [animal])

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CPM Vaccines, VPDs

On The Horizon (Over the Rainbow?)

More combination vaccines
Naked DNA antigen-producing gene injected,
incorporates into host DNA to produce antigen
(oncogenic???)
Vaccines against HIV, tuberculosis, malaria, HSV,
gonorrhea, syphilis, chlamydia, E. coli, et al.
Vaccines as treatment for cancer
Edible vaccines (insert antigen-producing gene in
potatoes, bananas), skin-patch vaccines
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CPM Vaccines, VPDs

WHO Immunization Recommendations (Children)

Vary from country to country, depending on disease burden,
resources, priorities
WHO recommended vaccines:
BCG
DTP: diphtheria, tetanus, pertussis
Haemophilus influenzae type B (hib)
hepatitis B
Human papillomavirus (HPV)
measles or MMR
pneumococcal (conjugate)
OPV (oral polio vaccine), w/ at least 1 dose IPV
rotavirus
rubella
japanese encephalitis, yellow fever
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CPM Vaccines, VPDs

http://www.who.int/immunuzation/policy/
immunization_schedules/en/

Immunization Recommendations, 2014 (Children)

WHO

BCG
DTP
HIB
hepatitis B
measles or MMR
pneumococcal
polio, OPV (live)
rotavirus

CPM Vaccines, VPDs

United States

no BCP
DTaP
HIB
hepatitis B
MMR
pneumococcal
polio, IPV (inactivated)
rotavirus
+ varicella
+ influenza
+ hepatitis A
www.cdc.gov/vaccines/recs/
schedules/ default.htm

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Immunization Recommendations, 2014 (Children)

Birth 2 m 4 m 6 m 12m 15m 18m <2y 2-3y 4-6y
hepatitis B

rotavirus

DTaP

Hib

3 or 4

PCV

IPV

4
1

Influenza
MMR, VZ
hepatitis A

2
1, 2
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CPM Vaccines, VPDs

www.cdc.gov/vaccines/schedules/hcp/
child-adolescent.html

Immunization Recommendations, 2014

(Adolescents)

Recommended for 11- and 12-year olds

Vaccines
Meningococcal (MCV4)
Booster against tetanus, diphtheria, pertussis (Tdap)
Human papillomavirus for girls
2011: Human papillomavirus for boys
Influenza (annual)

32

CPM Vaccines, VPDs

www.cdc.gov/vaccines/schedules/hcp/
child-adolescent.html

Immunization Recommendations, 2014

(Adults)

Catch up, if necessary (HPV, MCV, VZ, MMR)

Every 10 years

Booster against tetanus, diphtheria (Td), (substitute 1 dose of Td with

Tdap)

Annually

Influenza

Age 60 years
Zoster

Age 65 years

Pneumococcal (polysaccharide)

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CPM Vaccines, VPDs

www.cdc.gov/vaccines/schedules/hcp/
child-adolescent.html

Immunization Recommendations
(Health Care Workers)

Hepatitis B
Influenza (annually)
Measles, mumps, rubella*
Varicella*
Tetanus, diphtheria, pertussis
Meningococcal (only for microbiologists
routinely exposed to N. meningitidis)
* if no evidence of immunity
Adapted from http://www.immunize.org/catg.d/p2017.pdf

CPM Vaccines, VPDs

34

Immunization Recommendations
(Travelers)

Varies by country
May include

Japanese encephalitis
Meningococcal
Rabies
Typhoid
Yellow fever

Country-specific info:
wwwn.cdc.gov/travel/destinations/list

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CPM Vaccines, VPDs

Who Is This?

36

CPM Vaccines, VPDs

Mr. Ali Maow Maalin

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CPM Vaccines, VPDs

Who Is This?

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CPM Vaccines, VPDs

One More Vaccine Term

Vaccine efficacy percent reduction in incidence
of disease among people who were vaccinated
compared to incidence in unvaccinated people
Mumps vaccine 1 dose 78% effective
Mumps vaccine 2 doses 88% effective
Second dose recommended in early 1990s
Explanation of NHL outbreak: unvaccinated?
primary vaccine failure? secondary vaccine
failure?
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CPM Vaccines, VPDs

Impact of Vaccines, United States

Annual Cases
DiseasePre-vaccine era
Smallpox
48,164
Diphtheria
175,865
Pertussis
147,271
Tetanus
1,314
Polio, paralytic 16,316
Measles
503,282
Mumps
152,209
Rubella
47,745
Congenital rubella 823
H. flu <5 years20,000 est.

Cases in
2014*
0
1
27,878
21
0
554
1,100
7
0
402

percent
decrease
100
>99.9
82
98
100
99.9
99.3
>99.9
100
98

*Through week 52 ending Dec. 27, 2014

CPM Vaccines, VPDs

40

www.cdc.gov/mmwr/preview/mmwrhtml/
mm6352md.htm?s_cid=mm6352md_w