Shingles vaccine: study note

Two licensed shingles vaccines are available in the UK: Zostavax® and Shingrix®.

	Zostavax®	Shingrix®
Live vaccine?	Live attenuated vaccine	Recombinant vaccine (Not live)
Strain/ component	Derived from the OKA/Merck strain of the Varicella Zoster Virus	Contains varicella-zoster virus glycoprotein E antigen produced by recombinant DNA technology, adjuvanted with AS01B
Route	The vaccine is given IM or Subcutaneous, preferably in the deltoid region of the upper arm. For individuals with a bleeding disorder, it should be given by deep subcutaneous injection	IM, preferably in the deltoid region of the upper arm. Subcutaneous administration is not recommended. It should be given IM cautiously in individuals with thrombocytopenia or any coagulation disorder.
Dose	Adults should receive a single 0.65ml dose. Revaccination is not recommended.	Two doses of 0.5ml of Shingrix® a minimum of 2 months apart.
With another vaccine	If given simultaneously as another vaccine, the vaccines should be given at separate sites, preferably in different limbs. If given in the same limb, they should be given at least 2.5cm apart.	If given simultaneously as another vaccine, the vaccines should be given at separate sites, preferably in different limbs. If given in the same limb, they should be given at least 2.5cm apart.
Preparation	A lyophilised preparation for reconstitution with a diluent	A white powder for reconstitution with diluent and is injected as a suspension.
Adverse effects	Injection site reactions including: – erythema (redness), – warmth at the injection site, – pain, – swelling, – pruritis (itching) – haematoma, Also – pain in the arm or leg and headache. Varicella (chickenpox) like illness – Rare (0.01%)	Pain at the injection site, myalgia, and fatigue.
Contraindications	– Confirmed anaphylactic reaction to a previous dose of varicella virus-containing vaccine or any component of the vaccine. – women of childbearing age/pregnant. – severe immunosuppression	Confirmed anaphylactic reaction to any component of the vaccine.

Efficacy:

Zostavax®	Shingrix®
Reduction in the incidence of shingles: ≥60 years – about 50 – 65%. ≥70 years – about 38% Reduction in the incidence of postherpetic neuralgia (PNH): 66- 81%. The duration of protection following a single dose is unknown. Likely to be 3 years or longer. In the UK, vaccination programme effectiveness reduced from 69% to 45% over 3 years.	One and two-dose effectiveness: In over 65 years – one dose 56.9% and two doses – 70.1% effective Two-dose effectiveness against postherpetic neuralgia – 76%. RCT and clinical trials found vaccine efficacy – ≥ 50 years – 97.2% ≥70 years – 91.2% Immunocompromised patients (including NHL and CLL) – 87.2%

National programme

• Routine vaccination for people aged 70 years, using Zostavax®
• A catch-up programme was rolled out to those aged 70-79 years in a phased approach.

It is not recommended
– for use from age 50 routinely. (Although it is effective and licensed in this age group, routine use is not recommended, as the burden of shingles disease is generally not as severe)
– It is not cost-effective to use over 80 years old (due to the vaccine’s lower effectiveness in older individuals).
– not indicated for the prevention of primary VZV infection (chickenpox) and should not be used in children and adolescents.
– Zostavax® or Shingrix® are not recommended for post-exposure prophylaxis or as a treatment for chickenpox, shingles, or postherpetic neuralgia (PHN).

• Immunocompromised patients who are eligible for shingles vaccine (70-79 years) but unable to take live vaccine – should receive Shingrix®. However, people with lower levels of immunosuppression should be offered Zostavax® instead due to the limited supply of Shingrix®.

Specific situations

Individuals who have shingles	Individuals who have shingles should wait until symptoms have ceased before being considered for shingles immunisation.
Recurrent shingles	Concurrent use of aciclovir, high-dose IVIG or varicella immunoglobulin
1. It is a rare complication of Zostavax®. 2. There is a possibility that it could be transmitted to a susceptible person. As a precautionary measure, the rash area should be covered when in contact with a susceptible (chickenpox naïve) person until the rash is dry and crusted. 3. Prophylactic aciclovir can be considered in vulnerable patients exposed to varicella-like rash in a recent vaccine. 4. If the person who received the vaccine is immunosuppressed, they should avoid contact with susceptible people until the rash is dry and crusted due to the higher risk of virus shedding. 5. Contact tracing is not required if an immunocompetent person develops a localised vesicular rash following Zostavax® vaccination. 6. A vesicle fluid sample should also be sent for analysis to confirm the diagnosis and determine whether the rash is vaccine-associated or wild-type. This service is available at the Virus Reference Department (VRD) at Public Health England, Colindale.	Zostavax® should be delayed in individuals who are being – treated for non-varicella zoster infections with either oral or intravenous antivirals (such as aciclovir)/receiving aciclovir prophylaxis until 48 hours after cessation of treatment or – high dose IVIG/ varicella-zoster immunoglobulin (VZIG) in the previous 6 weeks.
People developing a varicella-like rash after vaccination	1. It is a rare complication of Zostavax®. 2. There is a possibility that it could be transmitted to a susceptible person. As a precautionary measure, the rash area should be covered when in contact with a susceptible (chickenpox naïve) person until the rash is dry and crusted. 3. Prophylactic aciclovir can be considered in vulnerable patients exposed to varicella like rash in a recent vaccine. 4. If the person who received the vaccine is immunosuppressed, they should avoid contact with susceptible people until the rash is dry and crusted due to the higher risk of virus shedding. 5. Contact tracing is not required if an immunocompetent person develops a localised vesicular rash following Zostavax® vaccination. 6. A vesicle fluid sample should also be sent for analysis to confirm the diagnosis and determine whether the rash is vaccine-associated or wild type. This service is available at the Virus Reference Department (VRD) at Public Health England, Colindale.
Inadvertent vaccination of Zostavax® in immunosuppressed individuals	assess the degree of immunosuppression. Most people in this age group are varicella IgG+ve, so varicella-zoster immunoglobulin (VZIG) is unlikely to benefit, but prophylactic aciclovir may be considered. Those who develop rash should be assessed and considered for IV high-dose aciclovir.
Inadvertent vaccination of Zostavax® in pregnancy	Treat the inadvertent administration of the Zostavax® vaccine in a pregnant woman the same way as natural exposure to chickenpox infection.

Co-administration with another vaccine

	Zostavax®	Shingrix®
Inactivated influenza	can be given at the same time as inactivated influenza vaccination.	Should ideally be separated by an interval of at least 7 days to avoid incorrect attribution of potential adverse events. However, coadministration can be considered if rapid protection requires or individuals are likely to be lost to follow up.
23-valent pneumococcal polysaccharide vaccine	Zostavax® can be given at the same time
COVID-19 vaccination	should ideally be delayed for seven days after COVID-19 vaccination and vice versa	should ideally be delayed for seven days after COVID-19 vaccination and vice versa
MMR, yellow fever	four-week interval is observed between administration of MMR and Zostavax® vaccines

Severe immunosuppression

Categories	Example
Individuals with primary or acquired immunodeficiency states due to conditions including:	Individuals with chronic immune-mediated inflammatory disease who are receiving or have received immunosuppressive therapy
Individuals on immunosuppressive or immunomodulating therapy including:	● those who are receiving or have received in the past 6 months immunosuppressive chemotherapy or radiotherapy for any indication ● those who are receiving or have received in the previous 6 months immunosuppressive therapy for a solid organ transplant ● those who are receiving or have received in the previous 3 months targeted therapy for autoimmune diseases, such as JAK inhibitors or biologic immune modulators, including B-cell targeted therapies (including rituximab but for which a 6 month period should be considered immunosuppressive), monoclonal tumour necrosis factor inhibitors (TNFi), T-cell co-stimulation modulators, soluble TNF receptors, interleukin (IL)-6 receptor inhibitors., IL-17 inhibitors, IL 12/23 inhibitors, IL 23 inhibitors (N.B: this list is not exhaustive)
● moderate to high dose corticosteroids (equivalent ≥20mg prednisolone per day) for more than 10 days in the previous month ● long term moderate dose corticosteroids (equivalent to ≥10mg prednisolone per day for more than 4 weeks) in the previous 3 months ● any non-biological oral immune-modulating drugs e.g. methotrexate >20mg per week (oral and subcutaneous), azathioprine >3.0mg/kg/day; 6-mercaptopurine >1.5mg/kg/day, mycophenolate >1g/day) in the previous 3 months ● certain combination therapies at individual doses lower than stated above, including those on ≥7.5mg prednisolone per day in combination with other immunosuppressants (other than hydroxychloroquine or sulfasalazine) and those receiving methotrexate (any dose) with leflunomide in the previous 3 months	● moderate to high dose corticosteroids (equivalent ≥20mg prednisolone per day) for more than 10 days in the previous month ● long term moderate dose corticosteroids (equivalent to ≥10mg prednisolone per day for more than 4 weeks) in the previous 3 months ● any non-biological oral immune-modulating drugs, e.g. methotrexate >20mg per week (oral and subcutaneous), azathioprine >3.0mg/kg/day; 6-mercaptopurine >1.5mg/kg/day, mycophenolate >1g/day) in the previous 3 months ● certain combination therapies at individual doses lower than stated above, including those on ≥7.5mg prednisolone per day in combination with other immunosuppressants (other than hydroxychloroquine or sulfasalazine) and those receiving methotrexate (any dose) with leflunomide in the previous 3 months
Individuals who have received a short course of high-dose steroids (equivalent to >40mg prednisolone per day for more than a week) for any reason in the previous month.