Vaccination

Vaccination is the administration of a substance to induce the immune system to develop protection against a disease. Unlike passive immunization, which involves the administration of pre-performed antibodies, active immunization constitutes the administration of a vaccine to stimulate the body to produce its own antibodies. A vaccine is usually an antigenic, non-virulent form of a normally virulent microorganism. Vaccinations are a form of primary prevention and are the most effective form due to their safety, efficacy, low cost, and easy access. While the majority of vaccines are administered to young patients, some vaccines are targeted to diseases that occur in middle and old age, and are therefore administered to older patients.

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Overview

  • A vaccine creates immunity against 1 or several diseases in the form of antibodies. 
  • Vaccines induce protection by:
    • Utilizing pre-existing components of the immune response
    • Inducing the generation of antigen-specific memory cells
    • Utilizing both innate and adaptive immunity
  • Uses of vaccines:
    • Prevent a disease from infecting a patient: polio (oral polio vaccine (OPV))
    • Prevent recurrence of an existing infection: zoster (shingles)
    • Prevent disease development post-exposure: rabies
    • Prevent prenatal fetal infection: rubella
    • Prevent cancer: HPV (human papillomavirus)/HBV (hepatitis B)
  • Vaccine components:
    • Antigen: whole organism (live attenuated or killed) or subunit
    • Carrier: provides helper T-cell epitopes, the part of an antigen molecule to which an antibody attaches
    • Adjuvant: immunomodulatory molecules that potentiate the immune response when given in conjunction with the antigen (most common adjuvant used in human vaccines is aluminum salts)
Components of vaccines

Components of a vaccine

DC activator: dendritic cell activator
PAMP: pathogen associated molecular pattern

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Active and Passive Immunization

Active immunization

  • Mechanism of immunity
    • Live-attenuated or inactivated pathogens are injected into the body.
      • Live-attenuated vaccines: pathogens attenuated in their pathogenic effects (virulence), but still proliferative
      • Inactivated vaccines: inactivated pathogens or their purified components
    • The immune system responds by creating immunity.
      • Humoral response creates antibodies to the injected pathogens, providing immediate immunity.
      • Cell-mediated response, through helper T lymphocytes, builds an immune “memory.”
      • Subsequent encounters with the actual pathogen cause a more robust immune response because memory cells are already present.
  • Onset and duration of immunity
    • Takes a few days to weeks for immunity to develop
    • Lifelong immunity may be obtained.
    • Some vaccines require boosters as humoral response may wane over time. 
  • Limitations
    • Can only build immunity to known forms of the pathogen
    • The presence of passive antibodies (e.g., intravenous immunoglobulin (IVIG) or trans-placental antibodies in a newborn) blunts immune formation.
    • Immune memory may not be permanent; may require boosters
  • Examples
    • Live attenuated:
      • Measles
      • Mumps
      • Rubella
      • Varicella
    • Inactivated:
      • Pneumococcal
      • Meningococcal
Magnitude of immune response

Immunological basis of active vaccination. The arrows mark the time of vaccine administration.

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Passive immunization

  • Mechanism of immunity
    • Premade immunoglobulins are infused to provide immunity.
    • There is no immunologic reaction.
  • Onset and duration of immunity
    • The onset of provided immunity is immediate.
    • There is no self-perpetuating or ongoing immunity.
    • Homologous immunoglobulin (human) preparations mainly contain immunoglobulin G (IgG). Their average half-life is 21 days.
  • Limitations 
    • Allergic reactions and anaphylaxis can occur.
    • The production of preformed antibodies is time intensive and costly. 
  • Examples
    • Horse antisera against snake venom, botulinum toxin, and diphtheria toxin
    • Pooled human Ig against hepatitis A or B, measles, rabies, tetanus, and varicella zoster
    • Humanized monoclonal antibodies against the respiratory syncytial virus (RSV)

Types of Active Vaccines

Table: Types of active vaccines
Vaccine typeDescriptionProsConsExamples
Live attenuated
  • Microorganism loses its pathogenicity but retains capacity for transient growth within inoculated hosts.
  • Induces cellular and humoral responses
Induces strong, often lifelong immunity
  • May revert to virulent form
  • Often contraindicated in pregnancy and immunodeficiency
  • MMR (measles, mumps, and rubella)
  • OPV
  • Rotavirus
  • Varicella zoster virus
  • Yellow fever
  • BCG (Bacille Calmette-Guérin)
Inactivated
  • The pathogen is inactivated by heat or chemicals, maintaining epitope structure on surface antigens.
  • Mainly induces a humoral response
Safer than live vaccines, easy to manufacture
  • Weaker immune response
  • Booster shots usually required
  • Hepatitis A
  • Influenza
  • Japanese encephalitis
  • IPV (inactivated polio vaccine)
  • Rabies
SubunitIncludes only the antigens that best stimulate the immune systemLower chance of adverse reactions
  • Expensive
  • Weaker immune responses
  • Hib
  • HPB
  • HPV
  • Pertussis
  • Pneumococcus
  • Meningococcus
  • Shingles
Toxoid
  • Denatured bacterial toxin with an intact receptor binding site
  • Stimulates the immune system to make antibodies without the potential to cause disease
Protects against bacterial toxinsAntitoxin levels decrease with time, may require a booster
  • Diphtheria
  • Tetanus
Toxoids vaccines

Toxoids are bacterial toxins, rendered harmless and immunogenic by chemical inactivation.

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Side Effects and Complications

Common reactions

  • Usually not life-threatening
  • May occur within the first 3 days after vaccination
  • Local inflammatory reactions (redness, swelling, pain) in the area of injection 
  • Fever, muscle and joint pain, fatigue, and/or flu-like symptoms
  • A milder form of the disease may be caused by administration of live vaccinations (e.g., vaccination measles, arthralgia in rubella vaccination).

Specific complications

  • Potentially life-threatening
  • Anaphylactic reactions to vaccine ingredients (e.g., patients with severe egg allergy can’t receive influenza or yellow fever vaccination)
  • Neuritis, neuropathy (diphtheria and tetanus)
  • Seizures (MMR)
  • Guillain-Barré syndrome (Hib, tetanus)
  • Encephalitis (measles)
  • Meningitis (mumps)
  • Arthritis (MMR vaccination)
  • Thrombocytopenia (pneumococcal, MMR, influenza, TDaP (tetanus, diphtheria, pertussis))

Vaccination in the United States

Immunization schedules

  • Revised yearly by the Centers for Disease Control and Prevention (CDC) in cooperation with other regulating agencies
  • The timing of inoculation is designed to line up with routine well-child visits and provide age-appropriate protection to pathogens.
  • For children who fall behind on immunization, a “catch-up” schedule provides for optimal timing of immunizations.
  • Preterm infants should receive their vaccines according to their chronological age, without any correction. One exception: HBV is administered when weight exceeds 2 kg.
Table: When do children and teens need vaccinations?
Birth1 month2 months4 months6 months9 months12 months15 months18 months4 years11 years16 years
Hep B (hepatitis B)
DTaP/Tdap✔ (Tdap)
Hib (HiB)
IPV
PCV13 (pneumococcal conjugate)
RV (rotavirus, liquid)
MMR
Varicella (chickenpox)
Hep A (hepatitis A)
HPV✔ ✔
MCV4 (meningococcal conjugate)
Influenza (seasonal flu)2 doses first year, then 1 dose annually

Vaccine refusal

  • All states in the United States require vaccination for admittance to public school.
  • Vaccine refusal is a hotly debated topic and state laws vary in whether it is allowed and for what reasons.
    • Medical exemptions: all states
    • Religious exemptions: nearly all states
    • Philosophical exemption: approximately ⅓ of states

Special circumstances

  • Children living in close contact with pregnant and immunocompromised individuals:
    • Should still receive all routine immunizations 
    • Should not receive the smallpox vaccine
  • Patients who do not have functional spleens are at risk for infections with encapsulated organisms and should be vaccinated for:
    • Pneumococcus
    • Menigococcus
    • HiB
Table: Common vaccines by type
LiveViralAdenovirus, sabin polio, varicella, yellow fever, smallpox, influenza (intranasal), MMR, oral rotavirus
BacterialBCG, oral typhoid
KilledFullVirusSalk polio, rabies, hepatitis A, influenza (injection)
SubunitProtein-basedSubunit: hepatitis B (HBsAg), HPV (types 6, 11, 16, and 18), acellular pertussis (aP)
Polysaccharide based
  • Toxoid: diphtheria, tetanus (DT)
  • Pure: Hib, pneumococcal (PPSV23), meningococcal (MPSV4)
  • Conjugate (pure + toxoid protein): Hib, pneumococcal (PCV13), meningococcal (MCV4)
MMR: measles, mumps, and rubella
BCG: Bacille Calmette-Guérin (TB vaccine, not used anymore in the United States)
HBsAg: hepatitis B surface antigen
HPV: human papillomavirus
Hib: Haemophilus influenzae type b
PPSV23: Pneumococcal polysaccharide vaccine against 23 antigens
MPSV4: Meningococcal polysaccharide vaccine against 4 antigens
PCV13: Pneumococcal conjugate vaccine against 13 antigens
MCV 4: Meningococcal conjugate vaccine against 4 antigens

Mnemonic

The following mnemonic can help you remember the viral and bacterial live vaccine types: Attention Teachers! Please Vaccinate Small, Beautiful Young Infants with MMR Regularly!

Attention: Adenovirus

Teachers: Typhoid

Please: Sabin Polio

Vaccinate: Varicella

Small: Smallpox

Beautiful: BCG

Young: Yellow fever

Infants: Influenza (intranasal)

MMR

Regularly: Rotavirus

Common Pathogens Prevented by Vaccination

Viruses against which vaccination is protective

  • Measles: characterized by fever, malaise, cough, coryza, and conjunctivitis, followed by an exanthem; caused by the measles virus
  • Rubella: characterized by a mild illness with symptoms that can include a low-grade fever and sore throat, followed by an exanthem; caused by the rubella virus
  • Mumps: manifests initially as fever, muscle pain, headache, and poor appetite, followed by inflammation of several bodily organs, most commonly the parotid glands
  • Influenza: possible complications include ear infections as well as viral and secondary bacterial pneumonia
  • Rabies: 1 of the oldest and most feared human infections with the highest case fatality rate of any infectious disease; usually leads to progressive encephalopathy and death
  • Polio: spreads from the gastrointestinal (GI) tract into the anterior horn of lower motor neurons, causing asymmetric acute flaccid paralysis
  • Rota: the most common cause of diarrhea in infants and young children worldwide
  • Hepatitis A: the most common cause of acute hepatitis, characterized by prodromal symptoms of fever, malaise, and abdominal pain, followed by jaundice
  • Hepatitis B: the 2nd most common cause of acute hepatitis and the most common cause of chronic hepatitis

Bacteria against which vaccination is protective

  • Corynebacterium diphtheriae: causes diphtheria, which manifests with a sore throat, fever, swollen glands, and weakness. In advanced stages, diphtheria can damage the heart, kidneys, and nervous system.
  • Clostridium tetani: causes tetani, a nervous system disorder characterized by painful muscle spasms
  • Bordetella pertussis: causes whooping cough, which manifests with a paroxysmal whooping cough that persists for weeks and can be fatal
  • Streptococcus pneumoniae: the leading bacterial cause of pneumonia worldwide and a common cause of meningitis, bacteremia of undetermined cause, and otitis media
  • Haemophilus influenzae type b: Before the widespread use of Hib conjugate vaccines, Hib was the most common cause of bacterial meningitis and a frequent cause of other invasive diseases (e.g., epiglottitis, pneumonia, septic arthritis, bacteremia), particularly in early childhood.

References

  1. David W. Kimberlin et al. (2018). Red Book® 2018 Committee on Infectious Diseases; American Academy of Pediatrics. https://redbook.solutions.aap.org/chapter.aspx?sectionid=189639953&bookid=2205#:~:text=Active%20immunization%20involves%20administration%20of,natural%20infection%20but%20usually%20presents 
  2. Spencer JP et al. (2017). Vaccine Adverse Events: Separating Myth from Reality. Am Fam Physician.
  3. Robinson CL, Bernstein H, Poehling K, Romero JR, Szilagyi P. (2020). Advisory Committee on Immunization Practices Recommended Immunization Schedule for Children and Adolescents Aged 18 Years or Younger. MMWR Morb Mortal Wkly Rep. 69(5):130-132. doi: 10.15585/mmwr.mm6905a3. PMID: 32027628; PMCID: PMC7004394.
  4. U.S. Department of Health and Services. Vaccine Types. Vaccines.gov. Retrieved October 5, 2020, from https://www.vaccines.gov/basics/types
  5. Woodcreek Pediatrics. Mary Bridge Children’s Vaccination Schedule. Retrieved October 2, 2020, from http://www.woodcreekhealthcare.com/immunizations.html

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