WCS39 Immunization

Question 1

HK Childhood Immunisation Program

Answer 1

Recent changes:

• MMRV vaccine (2nd dose): P1 —> 18 months
• 9-valent HPV vaccine (1st, 2nd dose): P5, P6

Vaccines NOT in HK universal programme:

• ***Haemophilus influenza type b vaccine (very low incidence in HK)
• ***Rotavirus vaccine (no deaths)

Vaccines in HK:

1. BCG vaccine
2. Hep B vaccine
3. DTaP-IPV (Diphtheria, Tetanus, acellular Pertussis, Inactivated Poliovirus) vaccine
4. Pneumococcal vaccine
5. MMRV (新加Varicella) vaccine
6. HPV vaccine (female)

(Mumps (腮腺炎)
Measles (麻疹)
Rubella (風疹, 德國麻疹)
Varicella (水痘))

Question 2

Immunisation

Answer 2

Active: Antigen (whole / component)
- long-lasting response

Passive: Immunoglobulins (e.g. Zoster Ig, Hep B Ig)
- immune response last ***< few months

Question 3

Vaccine types

Answer 3

1. Live attenuated organism
   - OPV, **BCG, **Chickenpox, ***MMR
   - exception: Inborn errors of immunity (cannot give live attenuated)
2. Killed whole organism
   - whole cell Pertussis, ***IPV, HAV
3. Inactivated exotoxin
   - **diphtheria toxoid, **tetanus toxoid
4. Subunit
   - acellular Pertussis, pneumovax
5. Subunit conjugated (e.g. with protein —> make it more immunogenic)
   - **Haemophilus influenzae type B, **pneumococcal vaccine: PCV7, PCV10, PCV13

Question 4

Live attenuated vaccines

Answer 4

• Attenuated (weakened) form of “wild” virus / bacteria
• ***Must replicate to be effective
• Immune response ~ natural infection

Disadvantage:

• Severe reactions possible (e.g. with babies with Inborn errors of immunity)
• ***Interference from circulating Ab (↓ replication of live attenuated organism)
• Unstable

Question 5

Antibody and Live vaccines

Answer 5

Product given first

1. Vaccine: wait 2 weeks before giving Ab
2. Antibody: wait >3 months before giving vaccine

(E.g. Kawasaki Ab: high dose needed: 9 months separate from other vaccines)

Question 6

Inactivated vaccines

Answer 6

• Cannot replicate
• ***Minimal interference from circulating Ab (∴ no need separate from IVIG)

Disadvantages:

• Generally not as effective as live vaccines
• Generally ***3-5 doses
• Immune response mostly ***humoral (may have some T cell response)
• Ab titre fall over time

Question 7

Vaccination and Immunisation

Answer 7

Can have vaccination but no immunisation

• if host did not mount immune response to vaccine
• e.g. outdated vaccines

Primary vaccine failure: No response to vaccine at all
Secondary vaccine failure: have a response but lose it

Question 8

Immunological challenges for new vaccines

Answer 8

Ability to generate memory B + T cells in host immune system

Question 9

Vaccines

Answer 9

1. Haemophilus influenzae type b vaccine
2. Chickenpox vaccine (introduced in mid-2014)
3. Rotavirus vaccine
4. Influenza
5. Pneumococcal vaccine

Question 10

Barriers to overcome for universal Hib vaccination

Answer 10

1. ***Disease burden low in
   - Hong Kong (incidence of Hib meningitis <5 yo: 3 per 100,000)
   - Singapore
   - Korea
   - China
2. Cost of vaccines

Question 11

1. Haemophilus influenzae type b vaccine

Answer 11

• Relatively low disease prevalence in East Asia
• Conjugate Hib vaccine effective
• Risk-benefit ratio for individual infant is overwhelming for vaccination
• Issue of universal vaccination in HK not settled
• ONLY used in ***private sector in HK with 50% coverage
  —> Hib disease incidence already dropped to <1 per 100,000 under 5 yo

Question 12

2. Chickenpox vaccine (introduced in mid-2014)

Answer 12

• Composition: ***Live virus (Oka-Merck strain)
• Efficacy: 95% (65-100%)
• Duration of immunity: > 7 years
• Schedule:
  1st dose: **1 year old
  2nd dose booster: **18 months, introduced because of waning immunity

Question 13

Varicella

Answer 13

Varicella epidemiology

• Reservoir: Human
• Transmission: Airborne droplet, Direct contact with lesions
• Temporal pattern: Peak in ***winter and Early spring (US)
• Communicability: 1-2 days before —> 4-5 days after onset of rash (may be longer in immunocompromised)

Pathogenesis:
Respiratory transmission of virus
—> Replication in **nasopharynx and regional LN
—> Repeated episodes of **viraemia (Primary, Secondary, etc.)
—> **Multiple tissues (e.g. skin), including **sensory ganglia, infected during viraemia
—> **Crops of rashes (with various stages: 四代同堂)
—> Red —> **Vesicles —> Crusting

Varicella complications:

1. Bacterial infection of lesions
2. CNS manifestations (***Reye’s syndrome, Cerebellar ataxia)
3. Pneumonia (rare in children)
4. Death ~1 in 60,000

Groups at ↑ risk of complications of Varicella:

1. ***Normal adults (without prior chicken pox)
2. Immunocompromised person
3. Newborns with maternal rash onset within ***5 days before —> 48 hours after delivery
   - Ig not yet developed in mother even mother has viraemia

Congenital Varicella Syndrome:

• Result from maternal infection during pregnancy
• Period of risk may extend through first 20 weeks to pregnancy
• Atrophy of extremity with skin scarring, low birth weight, eye and neurologic abnormalities
• Risk ~2%

Question 14

Zoster following vaccination

Answer 14

• Most cases in children
• Risk from ***wild virus 4-5 times higher than from vaccine virus
• Mild illness without complications

Question 15

3. Rotavirus vaccine

Answer 15

Surface antigen

• VP4 neutralisation antigen
• VP7 neutralisation antigen
• 1st gen live RV in late 1990’s linked with intussusception after licensure
• 2nd gen live RV, necessary to do phase III trial
• RV vaccines are safe and efficacious (but only in industrialised, middle income countries)
• Not used in HK, most children manage diarrhoea very well —> minor morbidity

Question 16

4. Influenza vaccine

Answer 16

Recommended group:

1. Children 6-23 months (reduce deaths / hospitalisation)
2. Children 2-5 yo (reduce hospitalistion)
3. Pregnant women (reduce severity)
4. Elderly persons (>=65) in residential care homes
5. Long-stay residents of institutions for the disabled
6. Elderly >=65
7. Persons with chronic illness
8. Health care workers
9. Poultry worker (prevent flu to spread among animal and human)

Challenges in vaccination in healthy children:

• Influenza does not carry high mortality
• only childhood vaccine that requires annual re-vaccination
• uncertain time interval between vaccine availability and influenza starts to circulate
• School Outreach Vaccination in HK from 2019/2020 for all primary schools and kindergartens

Question 17

5. Pneumococcal vaccine

Answer 17

Over 92 different serotypes of pneumococci

Clinical diseases:

1. ***Meningitis (serotypes 10A, 15B, 19F, 23F)
2. ***Empyema (serotypes 1, 3, 5, 7F, 8, 19A)
3. ***Necrotising pneumonia (serotypes 3)
4. Septic shock

Efficacy (Not very good):

• 8% against clinical pneumonia
• 36% against CXR-positive pneumonia
• Serotypes 3 in PCV13 vaccine is not effective —> no reduction in IPD (invasive pneumococcal disease)

PCV13 additional serotypes (比其他疫苗多左3, 19A, 6A serotype) cause significant disease burden even with vaccination

Mechanism:
Immunisation
—> Immunogenic response (Vaccine type specific Ab (***IgG))
—> Direct protection against Colonisation (e.g. Nasopharynx) + Disease

Question 18

Pneumococcal disease and vaccine

Answer 18

• Heavy disease burden
• PCV10 ~ efficacy to PCV13
• 2+1 (2 priming dose + 1 booster) or 3+0 schedule —> similar impact
• serotype replacement and vaccine failure (***serotype 3)
  —> need to add other previously non-covered serotype
• surveillance of IPD (with ***serotype testing) is a MUST before and after PCV vaccination

Major barrier for using PCV is ***vaccine price

Question 19

COVID

Answer 19

Characteristics:

• ↓ Type 1 IFN
• ↑ TNF-α, IL-1/6/18
• Lymphopenia indicator of disease severity
• SARS Ab and memory B are short lived (<1 year)
• ***Intranasal route may be better for COVID vaccine

Question 20

Evolution of immunisation program and prominence of vaccine safety

Answer 20

Prevaccine
—> Increasing coverage
—> Loss of confidence due to adverse effects of vaccine
—> Outbreak
—> Resumption of confidence
—> Eradication
—> Vaccinations can be stopped