Vaccination
The introduction and widespread use of vaccines has resulted in:
o Global eradication of smallpox.
o Elimination of poliomyelitis caused by wild viruses.
o Dramatic reductions in the incidence rates of other diseases.
Measles, diphtheria, and rubella have been greatly reduced in
developed countries (>90%) and, if global vaccination efforts can be
sustained, may eventually be eliminated from many other countries
Definition: there are three major categories
Vaccine: A suspension of attenuated live or killed microorganisms (bacteria, viruses,
or rickettsiae), or fractions administered to induce immunity and thereby prevent
infectious disease.
Toxoid: A modified bacterial toxin that has been rendered nontoxic but retains the
ability to stimulate the formation of antitoxin.
Live vaccine is a microorganism that can replicate on its own in the host or can infect
cells and function as an immunogen without causing its natural disease.
Inactivated or subunit vaccine is an immunogen that cannot replicate in the host.
A nucleic acid-based vaccine (usually DNA) cannot replicate in humans, is taken up
by cells, in which it directs the synthesis of the vaccine antigen(s).
Comparative Properties of Active Vaccines
LIVE VACCINES SUBUNIT, INACTIVATED GENETIC VACCINES (DNA
VACCINES BASED)
Able to replicate in the host Unable to replicate in the Stimulate synthesis of
host antigens only in cells
Attenuated in pathogenicity Cannot multiply or revert to
pathogenicity
Elicit antibodies & cell- Elicit mostly antibodies Elicit mostly cell-mediated
mediated immunity immunity
May elicit broader immune Generally less reactogenic Sustained immunologic
responses stimulation
May require fewer doses Nontransmissible to another
person
Longer lasting protection Variable efficacy Immunogenic potency
Immunologic basis of vaccination
Two major approaches to active immunization have been employed:
o The use of live (generally attenuated) infectious agents.
o The use of inactivated, or detoxified, agents or their extracts.
Immune response to vaccine antigens
o Activation of APCs, involving
Processing of antigens by the lysosomal or cytoplasmic pathways.
Expression of co-stimulatory factors and chemokine receptors at the
cell surface.
Secretion of certain cytokines.
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o Activation, replication, and differentiation of T and B lymphocytes
generation of large pools of memory cells of both types.
o Incorporation of sufficient B cell epitopes to generate strong neutralizing
antibody responses.
o Incorporation of sufficient T-cell determinants that bind with high affinity to
the major regional HLA haplotypes so that the complex is recognized by the
T-cell receptor.
o Long-term persistence of intact antigen, preferably as aggregates complexed
with antibody allows the continuing production of cells that secrete
antibody of higher affinity, and of memory B cells.
Immunologic properties of vaccines
Live, attenuated vaccines induce an immunologic response more similar to that
resulting from natural infection than do killed vaccines.
The live, attenuated viruses are believed to confer lifelong protection with one dose in
those who respond.
Killed vaccines do not induce permanent immunity with one dose, making repeated
vaccination and boosters necessary to develop and maintain high levels of antibody.
Polysaccharide vaccines tend to induce T-cell-independent immune responses that do
not produce booster responses on repeated injections and have poor immunogenicity
in infants and young children.
Protein antigens tend to generate a T-cell-dependent immune response with induction
of immunologic memory, booster effects on repeat administration, and good
immunogenicity in infants and young children.
Vaccine types and vaccination in different diseases
N.B: SAR = severe allergic reaction LR = local reaction
Toxoids
Tetanus-diphtheria
Type (route and dose): Adsorbed toxoids (im, 0.5 mL)
Schedule:
Primary: 3 doses; first 2, 4- 8 weeks apart; 3rd dose after 6-12 months.
Booster: every 10 years; alternatively, a single dose may be given at age 50 years for
persons who have completed full pediatric series, including teenage booster (Tdap).
Indications: For children ≥7 years old and adults
Precautions and contraindications: SAR after a previous dose.
Adverse effects: LRs are common; occasional systemic symptoms; Arthus-like reactions.
Tdap
Type (route and dose): toxoids of diphtheria & tetanus + acellular pertussis (im, 0.5 ml)
Schedule: Primary: not used for this purpose
Booster: single dose for adolescents age 11-12 years who have completed childhood
DTP/DTaP course and single dose for adults 19-64 years.
Indications: adolescents & adults 11-64 years who need boosting for any of the 3 antigens
Precautions and contraindications: SAR to a vaccine component.
Encephalopathy within 7 days of receipt of vaccine with pertussis component,
Guillain Barre ≤ 6 ws after previous dose of tetanus toxoid-containing vaccine.
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Adverse effects: LRs include erythema, swelling, and pain, systemic reactions include
fever, fatigue, and gastrointestinal headache, symptoms
DTaP (multiple preparations available)
Type (route and dose): toxoids of diphtheria and tetanus + acellular pertussis (im)
Schedule: Primary: 1st at 2 months, 2nd and 3rd at 4-8 week interval, 4th at 15-18 months
ct age; 5th at 4-6 years of age. Fifth dose not needed in children given primary series.
Indications: For infants and children ≤ 7 years old
Precautions and contraindications: SAR after a previous dose or to a vaccine
component; encephalopathy within 7 days of previous dose, high fever (> 40 °C), seizure.
Adverse effects: same as above + seizures.
Inactivated bacteria vaccines
Hib
Type (route and dose): Conjugated polysaccharide (im)
Schedule: Primary: 3 doses at 2, 4, and 6 months; 4th dose at 12-15 months;
Indications: All infants and children ≤ 5 years old
Precautions and contraindications: SAR after a previous dose; age 12 months old; chronic liver
disease; homosexual men;
Precautions and contraindications: Safety in pregnancy is unknown; SAR after a
previous dose
Adverse effects: LRs with pain, occasional fever & headache
Hepatitis B (Recombivax HB and Engerix)
Type (route and dose): Recombinant-HBsAg (im, adult and pediatric formulations)
Schedule: Primary: 3 doses at 0, 1-2, and 4-6 months of age, booster: not routine
Indications: Health care workers, persons in areas of intermediate to high endemicity:
others at risk for contact with blood, or blood contaminated medical or dental instruments
Precautions and contraindications: Pregnancy is not a contraindication in high risk
Adverse effects: Mild. LR in 3%-29% of cases; fever in 1%-6%
Hepatitis A and B antigens combined (Twinrix)
Type (route and dose): Inactivated hepatitis A virus plus recombinant HBsAg (im 1 ml.)
Schedule: Primary: 3 doses at 0, 1, and 6 months; accelerated schedules exist
Indications: Travelers ≥18 years old at risk for both hepatitis A and B; give at least 2
doses of vaccine prior to departure to provide protection against hepatitis A
Precautions and contraindications: Safety in pregnancy is unknown; SAR
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Adverse effects: LRs, headache and fatigue
Poliomyelitis
Type (route and dose): Killed poliomyelitis virus, trivalent, (sc or im, 0.5 mL)
Schedule: Primary: 3 doses, first 2 at 4- to 8- week interval; 3rd dose 6-12 months after
2nd dose; booster: 1 adult, lifetime dose with travel to regions of endemicity
Indications: routine in infants, travel to countries where polio is endemic
Precautions and contraindications: SAR after a previous dose, pregnancy is a relative
contraindication
Adverse effects: Mild LRs
Influenza
Type (route and dose): Inactivated whole and split influenza A and B virus (im, 0.5 mL)
Schedule: Annual vaccination with current vaccine
Indications: Persons > 6 months old with high-risk conditions; persons with chronic
diseases; healthy adults >50 years old; healthy children aged 6-23 months; health care
workers; travelers at risk; pregnant women in 2nd or 3rd trimester during flu season
Precautions and contraindications: SAR after a previous dose
Adverse effects: Mild LRs; occasional systemic reaction of malaise or myalgias
Japanese B encephalitis
Type (route and dose): Inactivated virus (sc, 1.0 mL)
Schedule: Primary: 3 doses at days 0, 7, and 30; booster-1 dose at 24-month interval
Indications: Travelers to area of risk with rural exposure or prolonged residence
Precautions and contraindications: Pregnancy; history of multiple allergies,
Adverse effects: Local, mild reactions, fever, myalgias, headache, or gastrointestinal
upset, respiratory distress, sudden death or encephatomyelitis are rare
Rabies
Type (route and dose): inactivated virus in HDCV, PCEC, RVA (im, 1.0 ml)
Schedule: Preexposure 3 doses at days 0, 7, and 21 or 28: booster: depends on risk
category and is based on serological test results; postexposure prophylaxis: rabies Ig day
0 and vaccine given days 0, 3, 7, 14, and 28
Indications: travelers, developing regions; medical workers in areas of endemicity
Precautions and contraindications: Allergy to previous doses; given in pregnancy
Adverse effects: LRs: pain, erythema, swelling; mild systemic reactions: headache,
nausea, aches, and dizziness; immune complex like reactions with booster dose of HDCV
Vaccines in special hosts
Children
It is currently recommended that all children receive
DTaP Polio Measles
Mumps Rubella HIB
Hepatitis B Varicella Rotavirus
Adolescents
At 11 to 12 years of age
A booster dose of Td for those persons who completed a primary series and received their
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last dose of a vaccine containing tetanus and diphtheria toxoids at school entry.
3-dose hepatitis B vaccine if not previously received (0, 1 to 2 months, and 4 to 6 ms).
2nd dose of MMR if not previously given A dose of varicella vaccine
Pneumococcal vaccine. Influenza vaccine. Hepatitis A vaccine.
Adults
If not previously immunized to diphtheria and tetanus primary immunizing course
(three doses of Td administered at time zero, 4 to 8 weeks, and 6 to 12 months) with
boosters administered every 10 years.
Routine immunization against polio is not recommended for adults unless they are at
risk of exposure.
Rubella vaccine should be administered to women of childbearing age.
Pneumococcal polysaccharide vaccine is recommended for administration to the
elderly and the chronically ill.
Hepatitis B virus vaccine is recommended for individuals at high risk of exposure to
hepatitis B virus.
Travel
Yellow fever vaccine Measles vaccine Polio vaccine
Boosters for tetanus and diphtheria
Travelers to specified areas
Plague Typhoid Rabies
Hepatitis B Hepatitis A Japanese encephalitis
Occupational E xposure
Hepatitis B vaccine Rubella vaccine (might transmit rubella to pregnant patients)
Measles vaccine Influenza vaccine Varicella vaccine
Pregnancy
Because of unknown but theoretical risks to the fetus, immunization of pregnant
women is generally avoided.
Vaccines that can be given to pregnants
Combined tetanus-diphtheria toxoids.
Influenza virus vaccine.
Hepatitis B.
Live virus vaccines are contraindicated in pregnancy with the exceptions of
o Polio vaccine
o Yellow fever virus vaccine administered if the risk of exposure to the
disease is great.
Immunocompromised States
Live virus vaccines are not administered.
Inactivated vaccines are indicated.
Avoid administration of OPV vaccine to immunocompromised individuals or their
household contacts.
IPV should be used under those circumstances.
Efficacy of inactivated vaccines in immunocompromised individuals may be less than
that in healthy patients.
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Human Immunodeficiency Virus
Live attenuated vaccines are contraindicated.
Exceptions include
o BCG given to patients with AIDS.
o Measles-containing vaccine.
o IPV should be used in place of OPV for all HIV-infected persons.
o Live attenuated MMR vaccine.
o Measles vaccine (not in severely immunocompromised).
o Pneumococcal and influenza vaccines.
o Some protection may be provided by toxoids.
Postexposu re Immu nization
For certain diseases, administration of vaccine or IG soon after exposure can prevent
or attenuate the expression of the disease. For
Examples:
o IG within 2 weeks of exposure to hepatitis.
o RIG and rabies vaccine in the immediate postexposure period.
o Combined tetanus-diphtheria toxoids.
o IG administered within 6 days of exposure to measles (prevent or modify
illness).
o Overt manifestations of rubella can be minimized by postexposure
administration of IG (may not prevent viremia and fetal infection).
o Varicella vaccine: studies suggest its usefulness in postexposure prophylaxis.
Immunization in patients with chronic liver disease
Hepatitis B vaccine Hepatitis A Pneumococcal Hemophilus influenzae
Influenza vaccine Diphtheria and Tetanus vaccines Meningococcal vaccine
Vaccines under trial for major health problems
Schistosoma vaccines
Malaria
Leishmania vaccine
Phase 3 clinical trials.
Live attenuated, inactivated.
Given to residents of endemic countries.
HIV
Recombinant vaccinia virus expressing human immunodeficiency virus type 1
(HIV-1) glycoprotein (gp) 160.
Recombinant HIV-1 gp120 (rgp120) expressed in Chinese hamster ovary (CHO)
cells has been formulated into a vaccine that is in Phase III clinical studies
HCV
Staphylococcus aureus vaccine
Phase 3 clinical trials.
Conjugated.
High risk, those with eczema, those with neutrophil dysfunction.
Inactivated whole-cell V. cholerae vaccine given by the oral route.
Inactivated enterotoxigenic Escherichia coli (ETEC) vaccine given by the oral route is
under active development.
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