ZOSTER VACCINES: MYTHS

AND FACTSKenneth Chatriand, PharmD.

DISCLOSURES:

• The speaker has no conflict of interest to disclose

• The speaker will use brand names of the zoster vaccines to clarify/simplify

the presentation; no specific product endorsement is implied.

LEARNING OBJECTIVES:

At the conclusion of the presentation, the learner should be able to:

1. Understand the epidemiology of the varicella zoster virus (VZV)

2. Explain common and rare complications of VZV

3. Know the recommendation per ACIP guidelines on patients who

qualify for a vaccine

4. Answer common patient questions regarding use of the

vaccines available

PATHOPHYSIOLOGY

PATHOPHYSIOLOGY

Varicella is a member of the herpesvirus group specifically called

the varicella zoster virus (VZV)

Incredibly virulent by respiratory transmission

Replication occurs in lymph nodes and nasopharynx

Short survival outside body tissues

PATHOPHYSIOLOGY

Primary viremia (no lesions or chickenpox) occurs typically

within 1 week after inoculation and spreads to other organ

systems including liver, spleen, and ganglia

Secondary viremia occurs after further replication and

includes infection of the skin (chickenpox)

Incubation period ranges from 10 to 21 days but may be

longer in immunocompromised individuals

PRIMARY INFECTION

Children typically do not have any symptoms prior to lesions and the rash is the first sign of an active infection

Mild prodrome may be present a couple of days prior to lesions in adults

Includes general malaise and a fever

Rash with lesions generally first appears on head and is typically most

concentrated on trunk/thorax.

Lesions also occur on mucous membranes including respiratory tract, vagina, and

eyes.

Clear fluid vesicles may rupture and are very purulent until they “dry and crust”

Lesions may be present in multiple forms and give way to crops

CLINICAL COURSE

Healthy Children: Generally mild and includes malaise,

pruritis (itching), and low grade fevers up to 102°F

Adults and immunocompromised individuals tend to have

more severe symptoms with a higher incidence of

complications

COMPLICATIONS

Risk varies with age but frequently occur more in people older than 15 years of age

Secondary infections of skin lesions

Mom was right…don’t itch

Pneumonia

Meningitis, encephalitis, cerebellar ataxia and other central nervous system manifestations.

Hospitalization: 2-3 incidences per 1,000 in children and 8 incidences per 1,000 cases in adults

Death: 25 per 100,000 cases in adults and 1 per 100,000 in children

Shingles

SHINGLES

Shingles is due to the reactivation of the VZV virus

Risk Factors include old age, poor immune function, and early

onset of chickenpox (before 18 months of age).

Symptoms include headache, fever, and other non-

specific symptoms

Symptoms then are followed by sensations of pain,

burning, itching, or parathesias (pin and needles

feeling).

SHINGLES

After 1-2 days or as long as up to 3 weeks a rash can start

Most common on torso but can appear on the face, eyes, or other

body parts

Rash is typically follows dermatone or a stripe or “belting” that follows

the nerve ganglia.

Commonly limited to one sided of the body and does not typically cross

the midline

Rash then becomes small blisters (vesicular) and can be weepy and

secrete an exudate – contagious to other people.

Vesicles eventually heal and form crust although pain can last

indefinitely.

COMPLICATIONS

Postherpetic neuralgia (PHN) is one of the biggest complications when

dealing with VZV.

Neuralgias typically follow banding of neurons disseminating from spinal cord

Usually involves upper body and face (trigeminal nerve)

When virus is reactivated in trigeminal branch it is termed zoster ophthalmicus

Ocular nerve can be assaulted and lead to blindness

Can also cause shingles oticus in the ear (Ramsay Hunt Syndrome type II)

Symptoms include hearing loss and vertigo

May last months, years, or life of patient

PREVENTION

We have two different vaccines approved for

the use of shingles prevention

Zostavax® (Live attenuated virus) Merck

Shingrix® (Adjuvanated Subunit) GlaxoSmithKline

ZOSTAVAX® VS SHINGRIX®

Zostavax®

FDA approved for 50 years and older

Same virus that is in Varivax® or ProQuad® although at

a much higher titer

19,400 Units vs 1,350 Units

Given with dose of 0.65mL subcutaneously

Reconstituted with sterile water and stored frozen

ZOSTAVAX® VS SHINGRIX®

Zostavax®

Primary Clinical Trial in adults 60-80 years of age

Over 38,000 adults with no prior history of zoster

Followed over 3.1 years after a single dose of vaccine

Compared with placebo group, vaccine group had a reduction of 51% in

zoster illness reported

Efficacy was higher among the younger participants (64% in 60-69yo)and

declined with increasing age (18% in ≥80yo)

Clinical trial in persons 50 through 59 years of age showed a reduction in

the risk of zoster by 69.8%.

Included more than 22,000 people

ZOSTAVAX® VS SHINGRIX®

Shingrix®

Randomized, placebo-controlled, phase 3 study

Total of 15,411 patients involved in study all age ≥ 50

Prospective study over 3.2 years

Efficacy was 97.2% (CI 93.7 to 99.0, p less than 0.001)

over ALL age groups

Funded by GSK

SHINGRIX®

What is an adjuvant???

An adjuvant is an ingredient of a vaccine that helps

create a stronger immune response in the patient’s

body.

Shingrix uses and adjuvant (AS01B also called HZ/su)

Acts like a satellite dish to help immune system respond to

specific antigens.

DOSING

Zostavax®

One 0.65mL dose administered Subcutaneously

FDA details age greater at 50, ACIP outlines 60 and older

Shingrix®

Two 0.5mL doses administered Intramuscularly given at 0, 2-6 months.

CDC recommendations are to get the 2nd dose in as soon as possible with regards to shortage of vaccine

Recommended age 50 and greater

COMMON SIDE EFFECTS

Zostavax®

Localized Reactions

Erythema, pain, tenderness,

swelling around injection site

(34%)

No increased risk of fever

VAERS – Listed 18 ADRs in 2018

Shingrix®

Localized Reactions

pain (78.0%), redness (38.1%), and

swelling (25.9%)

Systemic Adverse

myalgia (44.7%), fatigue (44.5%),

headache (37.7%), shivering

(26.8%), fever (20.5%), and

gastrointestinal symptoms (17.3%)

VAERS – Listed 1870 ADRs in 2018

Lets talk about why?

ZOSTAVAX® VS SHINGRIX®

VACCINE SHORTAGE

Why is there a shortage?

Lots of theories and falsehoods

Just a production issue

After CDC statement, demand skyrocketed

New factory in France for US use

9 Million vaccines produces last year

New batches coming out every 2 weeks

MYTHS AND FACTS

Giving multiple vaccines

Live vaccine vs non-live vaccine

Shingrix is not a live vaccine and can be given

concurrently with other vaccines

Wait 8 weeks after other zoster vaccines

MYTHS AND FACTS

I already had the zoster vaccine… ACIP is recommending Shingrix even if patient has prior vaccination of

Zostavax

Due to efficacy, especially is older age

Schedule?

Only proven study confirmed safe when administered 5 or more years after Zostavax

No data to support earlier however wait a minimum of 8 weeks between.

You should not be giving Zostavax at this time anyway!

MYTHS AND FACTS

I was vaccinated with varivax? When were they vaccinated?

Wait at least 8 weeks between dosing

Would they need another zoster vaccine?

YES! The chickenpox vaccine contains a weakened live virus,

which may cause latent infection. The risk of getting shingles from

vaccine is very low compared with natural infection but it is still

possible

MYTHS AND FACTS

I already have shingles… No specific length of time is recommended, but you should

generally wait until the rash has resolved before

vaccinating.

MYTHS AND FACTS

I already had Shingles Statistics show that 1 out of 4 Americans will develop shingles in

their lifetime.

Although it is common to have just 1 episode, it does not mean you will not have future outbreaks

MYTHS AND FACTS

Will this help my PHN? No vaccine is going to help alleviate any symptoms of post-

herpetic neuralgias

But is can prevent future outbreaks and risk for more

complications

MYTHS AND FACTS

I never had chickenpox…do

I really need this?

REFERENCES

Lal H, Cunningham AL, Godeaux O, et al, for the ZOE-50 Study Group. Efficacy of an adjuvantedherpes zoster subunit vaccine in older adults. N Engl J Med. 2015;372(22):2087-2096.

Chlibek R, Smetana J, Pauksens K, et al. Safety and immunogenicity of three different formulations of an adjuvanted varicella-zoster virus subunit candidate vaccine in older adults: a phase II, randomized, controlled study. Vaccine. 2014;32(15):1745-1753.

CDC. Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2007;56(no. RR-4):1-40.

CDC. Prevention of herpes zoster: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2008;57(no. RR-5).

Kimberlin DW, Whitley RJ. Varicella-zoster vaccine for the prevention of herpes zoster. N Engl J Med. 2007; 356(13):1338-1343

Levin MJ. Immune senescence and vaccines to prevent herpes zoster in older persons. Curr OpinImmunol. 2012;24(4):494-500.