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.
- Live-attenuated or inactivated pathogens are injected into the body.
- 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
- Live attenuated:
Immunological basis of active vaccination. The arrows mark the time of vaccine administration.
Image by Lecturio.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
Vaccine type | Description | Pros | Cons | Examples |
---|---|---|---|---|
Live attenuated |
| Induces strong, often lifelong immunity |
|
|
Inactivated |
| Safer than live vaccines, easy to manufacture |
|
|
Subunit | Includes only the antigens that best stimulate the immune system | Lower chance of adverse reactions |
|
|
Toxoid |
| Protects against bacterial toxins | Antitoxin levels decrease with time, may require a booster |
|
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.
Birth | 1 month | 2 months | 4 months | 6 months | 9 months | 12 months | 15 months | 18 months | 4 years | 11 years | 16 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
Live | Viral | Adenovirus, sabin polio, varicella, yellow fever, smallpox, influenza (intranasal), MMR, oral rotavirus | |
---|---|---|---|
Bacterial | BCG, oral typhoid | ||
Killed | Full | Virus | Salk polio, rabies, hepatitis A, influenza (injection) |
Subunit | Protein-based | Subunit: hepatitis B (HBsAg), HPV (types 6, 11, 16, and 18), acellular pertussis (aP) | |
Polysaccharide based |
|
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
- 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
- Spencer JP et al. (2017). Vaccine Adverse Events: Separating Myth from Reality. Am Fam Physician.
- 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.
- U.S. Department of Health and Services. Vaccine Types. Vaccines.gov. Retrieved October 5, 2020, from https://www.vaccines.gov/basics/types
- Woodcreek Pediatrics. Mary Bridge Children’s Vaccination Schedule. Retrieved October 2, 2020, from http://www.woodcreekhealthcare.com/immunizations.html