Exam 3- Lecture 5: VZV Vaccines

What is the Varicella Zoster Virus (VZV)?

• 1 of 8 human herpes viruses

  • Same family as herpes simplex viruses, EBV

• Establishes latency (virus is dormant) (neurons)

  • A life-long infection

What are the disease states for VZV?

Chicken Pox

• Occurs during 1st exposure; typically in children

• Fever is common 1-2 days after exposure

• Itchy rash w/ papules (bumps), which then turn into fluid-filled blisters, occurs 10-21 days after exposure

• Complications: encephalitis, pneumonia, sepsis, secondary bacterial infections

Shingles/ herpes zoster

• VZV reactivates & exits latency

• Itchy, painful rash in bands

  • Matches areas of skin innervated by infected ganglia

• Complications: post-hermetic neuralgia (common), vision & hearing loss, paralysis, encephalitis

What is the immune response against VZV?

• Innate immunity is important for recognizing virus at start of infection (presents antigens form virus to adaptive immune cell)

  • Macrophages, dendritic cells, NK cells

• Innate response stimulates T cells (CMI= cell-mediated immunity) & B cells (antibody production) to fight virus

  • Both CMI & antibodies are required for resolving infection

  • Response is antigen-specific

What is CMI important for?

Preventing reactivation

• Memory T cells (CD4 & CD8 T cells) are critical for preventing reactivation of VZV

What is in the Varicella Virus Vaccine (Varivax)?

• VAR

• Live vaccine type

  • AKA strain, attentuated (weak), does not establish latency

• 1350 PFU VZV (low dose of virus)

• 12-15 months recommended

• 2 doses

• Schedule: 0, 1 month

• SubQ

• Freezer

• Sterile water diluent

What is the Zoster Vaccine Live (Zostavax) → discontinued 11/2020?

• ZVL

• Live vaccine type (aka strain (attenuated), assuming they already have immune memory

• 19400 PFU VZV

• recommended > 60 years old

• 1 dose

• SubQ

• Freezer

• Sterile water diluent

What were the drawbacks of zostavax?

• Efficacy decreases w/ age

• Vaccine effectiveness wanes over time

• Contraindicated in immunocompromised

What is PFU?

“Plaque forming unit” = essentially a measure of # of viral particles

What is zoster subunit vaccine (shingrix)?

• RZV

• Recombinant vaccine type

• VZV glycoprotein E (gE) & AS01 adjuvant

• Recommended 50 years old

• 2 doses

• 0, 2-6 months

• Intramuscular

• Refrigerator

• AS01 adjuvant

What is shingrix formulation?

gE & AS01(B)

• Injecting a single protein (like gE) is usually not enough to generate a protective immune response

  • Generally, immunity from a live virus vaccine is better since it will express all of viral proteins & go through life cycle

• Improve immune response to gE, an adjuvant was added

What is AS01(B)?

An adjuvant for enhancing immune response

• QS-21- molecule from sap of soap tree

• Monophosphoyl lipid A (MPL)- non-toxic derivative of Lipid A

  • Lipid A- toxin from gram-negative bacteria → induces inflammation

  • Both factors stimulate antigen-presenting cells → leads to greater presentation of gE to T cells

  • Induces greater interferon responses

What does shingrix provide?

Effective long-term immunity

• Transient innate response by AS01(B) (0-72h)

• gE-specific response (months/yrs)

• Immunity is maintained out of 4-years post-vaccination. Longer studies pending

What is shrinking effective at preventing?

Shingles & PHN (post-hermetic neuralgia) in elderly

What does the CDC recommend even if you’ve received Zostavax?

Shingrix

What should the Shingrix vaccine be used in?

Immunocompromised

If you have shingles once, can you get it again?

• Yes!

  • Rates of recurrent infections are similar to rates of first occurrences

• CDC recommends getting vaccinated even if you’ve had shingles before

  • Still effective at boosting anti-VZV immunity

  • Not recommended during active infection