What shingles vaccine is recommended for individuals with a weak immune system, such as Shingrix (recombinant zoster vaccine), and what are the considerations for its administration?

Shingrix (Recombinant Zoster Vaccine) for Immunocompromised Individuals

Shingrix is the recommended and only appropriate shingles vaccine for individuals with a weak immune system, as it is a non-live recombinant vaccine that is safe and effective in immunocompromised patients, unlike the live-attenuated Zostavax which is absolutely contraindicated in this population. 1, 2

FDA-Approved Indications

Shingrix is FDA-approved for adults aged ≥18 years who are or will be at increased risk of herpes zoster due to immunodeficiency or immunosuppression caused by known disease or therapy. 2

• The vaccine is not indicated for prevention of primary varicella (chickenpox) and should only be given to patients with prior varicella immunity. 2

Dosing Schedule for Immunocompromised Patients

For immunocompromised adults, use a shortened vaccination schedule: 2, 3

• First dose at Month 0
• Second dose at 1-2 months (rather than the standard 2-6 months for immunocompetent adults)

The minimum interval between doses is 4 weeks; if administered earlier, the dose should be repeated. 4

Safety Profile in Immunocompromised Populations

The recombinant vaccine is non-live and therefore cannot cause varicella-zoster virus infection under any circumstances. 5, 6

Key safety considerations:

• Live-attenuated zoster vaccine (Zostavax) is absolutely contraindicated in immunocompromised patients due to risk of disseminated VZV infection. 1, 7
• Shingrix can be safely administered to patients on immunosuppressive therapy, including those on biologics, JAK inhibitors, rituximab, and glucocorticoids. 1, 3
• Studies in patients with hematologic malignancies on anti-CD20 therapies showed significant T-cell responses with RZV. 1

Common adverse reactions in immunocompromised patients (autologous HSCT recipients aged 18-49 years): 2

• Pain at injection site: 88%
• Fatigue: 64%
• Myalgia: 58%
• Headache: 44%
• Fever: 28%

Most reactions are transient and mild to moderate in severity. 6

Efficacy in Immunocompromised Populations

Real-world effectiveness demonstrates 70.1% vaccine effectiveness for 2 doses and 56.9% for 1 dose, emphasizing the importance of completing the full series. 8

• Vaccine effectiveness against postherpetic neuralgia is 76.0%. 8
• Protection persists for at least 8 years with minimal waning, maintaining efficacy above 83.3%. 4
• The vaccine maintains effectiveness even in patients on immunosuppressive therapy, though immune response may be somewhat reduced compared to healthy individuals. 1

Special Considerations for Specific Immunosuppressive Therapies

Patients on glucocorticoids:

• Concomitant low-dose glucocorticoids (prednisone equivalent <10 mg/day) do not adversely impact vaccine response. 1, 4
• Patients on chronic high-dose glucocorticoids (≥20 mg/day prednisone equivalent) qualify for vaccination starting at age 18. 7

Patients on TNF inhibitors:

• TNF-inhibitor treated patients develop significant humoral and cell-mediated responses, approximately half the response of healthy subjects but still clinically meaningful. 1
• No cases of varicella infection or zoster occurred in 600 patients on TNF-inhibitors who received vaccination. 1

Patients on JAK inhibitors (e.g., tofacitinib):

• Complete the full 2-dose Shingrix series before starting JAK inhibitor therapy whenever possible to maximize immune response. 4
• If urgent initiation is required, administer at least the first dose before starting therapy, with the second dose completed 1-2 months after starting the JAK inhibitor. 4

Patients on rituximab or anti-CD20 therapies:

• RZV produces significant T-cell responses even in patients with hematologic malignancies on anti-CD20 therapies. 1

Disease Flare Concerns

There has been theoretical concern that the AS01B adjuvant in Shingrix may cause flares of underlying inflammatory disease. 1

Evidence on disease flares:

• Retrospective reviews show conflicting results: 7% vs. 16% incidence of disease flare within 12 weeks of vaccination. 1
• Large database studies found no statistically significant increase in flares following vaccination. 4
• Post-hoc analysis of nearly 2,000 patients with self-reported inflammatory disease found similar high rates of vaccine efficacy and no new safety concerns. 1

The weight of evidence suggests flare risk is not significantly elevated, and the benefit of preventing herpes zoster outweighs this theoretical concern.

Timing Considerations

Prior herpes zoster infection:

• Vaccination is recommended regardless of prior shingles history, with vaccination ideally administered at least 2 months after acute symptoms resolve. 4, 7

Prior Zostavax vaccination:

• Adults who previously received Zostavax should receive Shingrix at least 2 months after the last Zostavax dose. 4, 7

During neutropenia:

• Shingrix is not contraindicated during neutropenia in cancer patients, as it is a non-live vaccine. 4
• Consider administering between chemotherapy cycles (>7 days after last treatment) when feasible to optimize vaccine response. 4

Critical Contraindications

The only contraindication to Shingrix is a history of severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine or after a previous dose. 2

Important Clinical Pitfalls to Avoid

• Never use Zostavax in immunocompromised patients—only Shingrix is appropriate. 1, 7
• Do not delay vaccination waiting for "optimal" timing; the risk of herpes zoster is immediate and substantial in immunocompromised patients. 4
• Ensure completion of the 2-dose series; single-dose effectiveness is significantly lower (56.9% vs. 70.1%). 8
• Do not confuse herpes zoster vaccination with varicella vaccination; patients without prior varicella immunity should receive varicella vaccine first if not contraindicated. 7