Vaccination

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)

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

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

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.

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

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.