Immunization

Passive and Active

• Passive immunization refers to the transfer of antibodies to confer protection
  • Mother-to-child transfer and immunoglobulins are examples
  • Hepatitis B
  • Chicken pox, that cannot recieve vaccine (in pregnant women, immunocompromised, baby exposed by mom at birth)
  • Measles, that cannot recieve vaccine
  • Hepatitis A, that cannot recieve vaccine or are high risk (liver disease)
  • Rabies
  • Tetanus
• Active immunization refers to a vaccine intended to provoke an immune response and therefore confer protection

Components

• Immunogen
  • Live attenuated: a weakened version of a pathogen that provokes an immune response without causing disease
  • Inactivated: killed pathogens, often provoking a weaker immune response than live, and may have problems with injection of unwanted proteins
  • Subunit: include proteins, polysaccharides and protein-polysaccharide conjugates
    • Polysaccharide antigens aren't particularly immunogenic
    • Conjugating polysaccharides to proteins generates a more robust memory response
• Adjuvant
  • Additional compound that stimulates immune response
  • Canada only uses aluminum salts (aluminum hydroxide, aluminum phosphate or potassium aluminum sulfate)
    • Rare side effects include subcutaneous nodules, granulomatous inflammation or contact hypersensitivity
• Preservatives
  • Prevent the vaccine from being contaminated with bacteria
  • Includes thimerosal, phenol, and 2-phenoxyethanol
• Additives
  • May contain trace amount of substances required during the purification process or to confirm vaccine quality

List of Vaccines

Vaccine	Notes
Bacille Calmette-Guérin Vaccine
Cholera and Enterotoxigenic Escherichia Coli
Diphtheria Toxoid
Haemophilus Influenzae Type B Vaccine
Hepatitis A Vaccine
Hepatitis B Vaccine
Herpes Zoster (Shingles) Vaccine
Human Papillomavirus Vaccine
Influenza Vaccine
Japanese Encephalitis Vaccine
Measles Vaccine
Meningococcal Vaccine
Mumps Vaccine
Pertussis Vaccine
Pneumococcal Vaccine
Poliomyelitis Vaccine
Rabies Vaccine
Rotavirus Vaccine
Rubella Vaccine
Smallpox Vaccine
Tetanus Toxoid
Typhoid Vaccine	Toxoid vaccine.
Varicella (Chickenpox) Vaccine
Yellow Fever Vaccine

• Live attenuated
  • MMR
  • Varicella (Zostavax)
  • Smallpox
  • Oral polio
  • Nasal spray influenza
• Killed
  • Hep A
  • Injectable influenza
  • Injectable polio
  • Rabies
• Subunit
  • Hib
  • Hep B
  • HPV
  • Pertussis, TdAP
  • Varicella (Shingrix)

Pathophysiology

• Depends on the specific vaccine
• Generally work by inducing specific IgG serum antibodies
  • BCG is the only T-cell-specific vaccine, although T-cell response may contribute to others
• Generally do not elicit a mucosal antibody response, so infection may only be stopped after already infecting a mucosal surface
  • Therefore, they do not induce sterilizing immunity
• Antigen-presenting cells are activated by a pathogen and in turn stimulate B and T cell response in the local lymph node
  • Live vaccines may travel throughout the body, activating multiple lymph nodes in different sites
  • Non-live vaccines only activate APCs that travel to the local lymph node, explaining why they may be given in multiple limbs at once
• Protein antigens trigger T-cells to help to activate B-cells in germinal centres
  • It can take a few weeks to produce IgG antibodies
  • IgG peaks within 4-6 weeks of primary immunization
• Polysaccharide antigens travel to lymphoid tissue where they bind B cells directly and trigger maturation into plasma cells
  • Without germinal centres, memory B cells are not produced
  • Need to be coupled to a carrier protein in order to generate a memory response
• Memory B cells require several days to redifferentiate into plasma cells upon reexposure

T-cells

• Th1: IFN-gamma and TNF-alpha to activate response against intracellular pathogens
• Th2: IL-4, IL-5, and IL-13 to activate response against extracellular pathogens such as helminths

Vaccination Schedule

• Canada's Provincial and Territorial Routine (and Catch-up) Vaccination Routine Schedule Programs for Infants and Children
• Canadian Immunization Guide: Recommended Immunization Schedules
• Canadian Immunization Guide: Immunization of Persons New to Canada

Adult Vaccination

Pneumococcus

• Conjugate better than polysaccharide
  • Prevnar: PC-7, then PC-10 and PC-13
    • Conjugated with diphtheria CRM197
    • Incremental benefit of vaccinating adults over and above vaccinating children is not high enough to warrant funding the vaccine
  • Pneumovax: PS-23
• In age >65 years or other high-risk groups, PC first, then PS 8 weeks later (recommended), though only PS is paid for in Ontario
• For high-risk groups, add a PS booster at 5 years
• If PS-23 already given, wait a year before giving PC-13

Influenza

• Trivalent has H1N1 and H2N3 (both flu A) and a flu B strain
• The quadrivalent adds a second flu B, for children who get more flu B
  • The first time someone receives the vaccine, they need a second booster
• The high dose is more effective but more expensive (Fluzone)
  • Trivalent vaccine
  • 24% increase in efficacy in the elderly (brings up to normal population)
• Ensure that higher risk patients are vaccinated as well as their household

Shingles/Varicella-zoster

• Live attenuated zoster vaccine (Zostavax)
  • Can be given if pred <20 mg/d or <14 days, low-dose methotrexate, azathioprine, 6MP, hydroxychloroquine, sulfasalazine, etc.
• Recombinatnt glycoprotein vaccine (Shingrix), 2 doses IM 2 months apart
  • Protection is at least 3-4 years, possibly longer

Asplenia

• Risk factor for encapsulated organisms: Streptococcus pneumoniae, Haemophilus influenzae type B, and Neisseria meningitidis
• Splenectomy, indications include trauma, cancer, ITP
• Also beware functional asplenia as in sickle cell disease and Howell-Jolly bodies
• Highest risk in the first 5 years, but can be up to 20 years out
• 2 weeks before elective or 2 weeks after unplanned emergent
• Recommended vaccines
  • Menactra (conjugate ACYW-135) + Bexsero (Men B, but not covered)
    • Second dose at 8 weeks, or later if given after splenectomy
  • HiB once
  • Pill-in-pocket amox/clav or levoflox to take on the way to ED if they get a fever
• Travel precautions: be careful about babesia in New England (fulminant sepsis and die), as well as malaria
• Dog bites are very high risk for severe Capnocytophaga
  • Prophylaxis with amox/clav x5 days

Close Contacts of Immunocompromised Patients

• In general, close contacts should receive all routine vaccines, including rotavirus and annual influenza
• Specific vaccines do have some caveats, however:
  • Rotavirus: the immunocompromised patient should not change diapers for 4 weeks after the infant receives their vaccine
  • Varicella-zoster virus (live): avoid contact only if the vaccinated household member develops a rash (rare)
  • Influenza (live, annual): avoid close contact for 2 weeks after the household member receives their vaccine
  • Poliovirus (live, oral): do not immunize close contacts with the live oral polio vaccine
  • Smallpox: avoid vaccinating close contacts if at all possible
• Of note, the strains in the MMR vaccine are not transmitted person-to-person, so it is safe for close contacts to be vaccinated with MMR

Catch-Up Immunization

Starting Between 1 and 6 Years

• First visit:
  • <4 years: DTaP-IPV-Hib, Pneu-C-13, MMR, Men-C-C
  • 4 years: DTaP-IPV-Hib, Pneu-C-13, MMRV, Men-C-C
  • 5-6 years: MMRV, DTaP-IPV, Men-C-C
• Second visit, at 2 months
  • If child is <5 years at was:
    • <15 months at first visit: DTaP=IPV-Hib, Pneu-C-13, Var
    • 15-23 months at first visit: Pneu-C-13, DTaP-IPV, Var
    • 2-3 years at first visit: DTaP-IPV, Var
    • 4 years at first visitDTaP-IPV
  • 5-6 years: DTaP-IPV
  • 7 years: Tdap-IPV
• Third visit, 2 months after second visit
  • <7 years: DTaP-IPV
  • 7 years: Tdap
• Fourth visit, 6-12 months after third visit
  • <4 years: DTaP-IPV
  • 4-8 years: MMRV, Tdap-IPV
• Fifth visit, 6-12 months after fourth visit and 4-6 years of age, only if child was <4 years at fourth visit
  • MMRV, Tdap-IPV
• Grade 7: HB, Men-C-ACYW, HPV-4
• 14-16 years: Tdap
• 24-36 years: Tdap
• ≥34 years: Td every 10 years
• 65 years: HZ, Pneu-P-23

Starting Between 7 and 17 years

• First visit
  • <13 years: Tdap-IPV, MMRV, Men-C-C
  • ≥13 years: Tdap-IPV, MMR, Var
• Second visit, 2 months after first visit
  • <13 years: Tdap-IPV, MMRV
  • ≥13 years: Tdap-IPV, MMR, Var
• Third visit, 6-12 months after second visit
  • Tdap-IPV
• Fourth visit, 10 years after third visit and only if child was <18 years at third visit
  • Tdap
• Grade 7: HPV-4
• Grade 7 or 8: HB
• Grade 7-12: Men-C-ACYW
• Grade 8-12: HPV-4
• Every ten years: Td
• 65 years: Pneu-P-23

Starting at 18 Years and Older

• First visit
  • Born before 1985: Tdap-IPV, MMR
  • Born between 1986 and 1996: Tdap-IPV, MMR, Men-C-C
  • Born in or after 1997: Tdap-IPV, MMR, Men-C-ACYW
• Second visit, 2 months after first visit
  • 18-25 years: MMR, Td-IPV
  • ≥26 years: Td-IPV
• Third visit, 6 to 12 months after second visit: Td-IPV
• Every 10 years: Td
• 65 years: Pneu-P-23

Contraindications

• Anaphylaxis to the vaccine or a component of the vaccine
• GBS within 6 weeks of immunization not attributable to other cause
• Usually deferred in cases of:
  • Current or recent acute febrile illness
  • Immunosuppressive therapy
    • Includes Prednisone ≥20 mg and duration >14 days
    • Generally wait at least 4 weeks following high-dose steroids, or up to 6-12 months or more for rituximab and some other biological response modifiers
    • For inactivated vaccines, wait 3 months after immunosuppression stops (since they're less immunogenic)
  • Pregnancy (live vaccines)
• Live vaccines
  • Immunocompromised
  • Suspicious family or personal history of immunodeficiency
  • Pregnancy (as a precaution)
  • Live influenza: severe asthma
• Rotavirus: congenital GI malformation or history of intussusception
• MMR/MMRV/VZV/HZV: active, untreated tuberculosis
• BCG or yellow fever: infant with signs and symptoms of AIDS

Acute Illness

• If significant nasal congestion is present that might impede delivery of LAIV to the nasopharyngeal mucosa, TIV can be administered or LAIV could be deferred until resolution of the illness.
• In infants with moderate-to-severe gastroenteritis, rotavirus vaccine should be deferred until the condition improves unless deferral will result in scheduling of the first dose beyond the recommended age limit.
• Administration of oral cholera and travellers' diarrhea vaccine should be postponed in persons with acute gastrointestinal illness.

IVIg and Transfusion

• IVIg at 2 g/kg, wait 11 months before giving live vaccines
• Even pRBC, should wait 4-5 months

Side Effects

• Common to very common AEFI
  • Vaccination site pain and swelling
  • Fever
  • Fever/rash a week after MMR
  • Large local reactions
    • Giant red swollen injection site or arm (not cellulitis, just watch and wait)
    • Commonly recur, especially tetanus-containing vaccines
• Uncommon AEFI
  • Hypotonic-hyporesponsive events (HHE) after infant vaccines (especially pertussis-containing vaccines)
  • Lymphadenopathy (MMR)
• Rare AEFI
  • Febrile seizure after MMR vaccine
• Very rare AEFI
  • Anaphylaxis after any vaccine
  • BCG can cause all sorts of things: lymphadenopathy, abscesses, disseminated

Vaccine Hesitancy

• Stay engaged with the patient/parent
• Use presumptive language (e.g. "it's time to give you your immunizations today")
• Use motivational interviewing
  • Open-ended question about specific question
  • Affirmation
  • Reflective listening
• Use clear language to present risks and benefits fairly
  • Use framing: "If you decide not to get the HPV vaccine, you increase your risk of getting HPV and cervical cancer" (instead of getting it decreases your risk); "the vaccine is 99% safe" (instead of 1% risk)
• Address pain and fear of pain (for children)
• Emphasize that herd immunity is not a guarantee, especially if there is an outbreak

Further Reading

• WHO: Six common misconceptions about immunization
• CPS: Working with vaccine-hesitant parents: An update

Further Reading

• Canadian Immunization Guide: Contraindications, Precautions and Concerns