Shingrix Vaccine Safety and Immunogenicity in People With HIV

Overseen By Maura M Manion, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must be taking: Antiretrovirals

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: Previous Shingrix, Severe allergies, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 2 months

225 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the Shingrix vaccine affects immune responses in people with HIV. Shingrix is already used to prevent shingles, a painful rash, in healthy adults and some immunocompromised individuals. The trial aims to determine if the vaccine is safe and effective for people with HIV. It seeks participants who are HIV-positive and have been on stable treatment, as well as healthy volunteers aged 50 and older. Participants will attend regular clinic visits and receive two doses of the vaccine over two months. As a Phase 1, Phase 2 trial, this research focuses on understanding how the vaccine works in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to important medical advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on a stable antiretroviral regimen for HIV, you can continue it during the study.

Is there any evidence suggesting that Shingrix is likely to be safe for people with HIV?

Research has shown that Shingrix is generally safe for people with weakened immune systems. Tests in various groups, including those over 18, found it to be safe. Common side effects include pain at the injection site, muscle pain, and tiredness, which are usually mild and resolve on their own. Since Shingrix is already approved to prevent shingles in adults with weakened immune systems, this offers reassurance for people with HIV. However, the study aims to learn more about how people with HIV specifically respond to the vaccine. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

The Shingrix vaccine is unique because it offers a promising new option for people with HIV to protect against shingles. Unlike other shingles vaccines that might not be as effective in immunocompromised individuals, Shingrix is designed to provoke a strong immune response, even in those with weakened immune systems. Researchers are excited about Shingrix because it uses an adjuvant system that boosts the body’s defensive response, potentially offering more robust protection than standard vaccines.

What evidence suggests that Shingrix might be an effective treatment for people with HIV?

Research has shown that Shingrix effectively prevents shingles, with a success rate of 91.3%. This vaccine is approved for healthy adults over 50 and adults over 18 with weakened immune systems. People with HIV face a higher risk of shingles, making this vaccine particularly important for them. The current trial specifically evaluates how people with HIV respond to Shingrix. Although specific data for this group remains limited, the vaccine's effectiveness in other groups suggests potential benefits for those with HIV. ^{4 6 7 8 9}

Who Is on the Research Team?

Maura M Manion, M.D.

Principal Investigator

National Institute of Allergy and Infectious Diseases (NIAID)

Are You a Good Fit for This Trial?

This trial is for adults over 18 with HIV who have a viral load under control and are on stable antiretroviral therapy, or elite controllers. Healthy volunteers over 50 can also join. Participants must agree to use contraception if they can become pregnant. Exclusions include pregnancy, breastfeeding, recent shingles or chickenpox vaccines, certain acute illnesses, immunoglobulin treatments within the past 90 days, and severe allergies to Shingrix components.

Inclusion Criteria

I am over 50, healthy, with no chronic issues or immune problems.

Individuals must meet all of the following criteria to be eligible for study participation: Able to provide informed consent.

Has a primary care provider.

Exclusion Criteria

Immunocompromised within the past 6 months.

Pregnancy or breastfeeding.

I have had chickenpox or shingles in the last month.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive two doses of Shingrix vaccine administered by intramuscular injection at months 0 and 2

2 months

2 visits (in-person)

Follow-up

Participants are monitored for safety and immunogenicity, with follow-up visits at months 3 and 12

10 months

2 visits (in-person)

Monitoring

Participants use a 28-day memory tool to record symptoms and have up to 4 phone calls to discuss side effects

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Shingrix

Trial Overview The study tests how well the Shingrix vaccine boosts immune response in people with HIV compared to healthy older adults. It involves at least four clinic visits over a year where participants receive two shots of Shingrix and provide blood samples through regular draws and possibly apheresis (a process that separates white blood cells from drawn blood).

How Is the Trial Designed?

Group I: Shingrix Experimental Treatment 1 Intervention

Shingrix will be administered in two 0.5-mL doses approximately 2 months apart.

Shingrix is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Shingrix for:

• Prevention of shingles in healthy adults over age 50 and in immunocompromised adults over age 18

Approved in European Union as Shingrix for:

• Prevention of herpes zoster (shingles) and postherpetic neuralgia (PHN) in adults 50 years of age and older

Approved in Canada as Shingrix for:

• Prevention of herpes zoster (shingles) in adults 50 years of age and older

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

SHINGRIX, a non-live herpes zoster vaccine, is safe for patients on immunosuppressive therapy, making it a suitable option for those with inflammatory bowel disease who are at higher risk for infections.

A case report of a 74-year-old woman with ulcerative proctosigmoiditis revealed blistering autoimmune skin disorders following SHINGRIX vaccination, suggesting a potential, though previously unreported, adverse effect of the vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blistering autoimmune skin reaction following SHINGRIX vaccination in an ulcerative colitis patient: Case report and literature review. Bell, H., Kamal, N., Wong, U.[2021]

A review of 2.5 years of post-marketing data from over 32 million doses of the adjuvanted recombinant zoster vaccine (RZV) found no significant safety concerns related to vesicular and bullous skin eruptions following vaccination.

The analysis showed that the number of herpes zoster (HZ) cases reported was lower than expected in the general population, suggesting that RZV vaccination does not increase the risk of HZ reactivation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Analysis of Spontaneously Reported Data of Vesicular and Bullous Cutaneous Eruptions Occurring Following Vaccination with the Adjuvanted Recombinant Zoster Vaccine. Pirrotta, P., Tavares-Da-Silva, F., Co, M., et al.[2022]

This study aims to evaluate the immune response to the Shingrix vaccine in 308 patients, including those with liver cirrhosis and liver transplant recipients, to understand how immunosuppression affects vaccine efficacy.

By measuring specific antibody and T cell responses at multiple time points, the research seeks to establish a routine test for monitoring vaccination success and its correlation with clinical protection against shingles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tiza-Titre increase and enhanced immunity through an adjuvanted, recombinant herpes zoster subunit vaccine in patients with liver cirrhosis and post-liver transplantation: a study protocol for a prospective cohort study. Vollmer-Raschdorf, S., Rashidi-Alavijeh, J., Voigt, S., et al.[2023]

In a phase 3 study involving 569 adults with haematological malignancies, the adjuvanted recombinant zoster vaccine (Shingrix) demonstrated a strong immunogenic response, with 80.4% of participants showing a humoral vaccine response compared to only 0.8% in the placebo group, indicating its efficacy in this high-risk population.

While the vaccine was more reactogenic than placebo, with higher reports of pain and fatigue, the overall safety profile was similar between the vaccine and placebo groups, suggesting that the benefits of vaccination outweigh the risks for immunocompromised individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity and safety of the adjuvanted recombinant zoster vaccine in adults with haematological malignancies: a phase 3, randomised, clinical trial and post-hoc efficacy analysis. Dagnew, AF., Ilhan, O., Lee, WS., et al.[2020]

Shingrix is an approved vaccine in Germany for preventing shingles (zoster) and its complications, specifically for adults aged 60 and older.

If patients experience bullous skin lesions after receiving Shingrix, it is important to consider the possibility of zoster disease and report any unexpected side effects to the appropriate medical authorities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Zoster disease after Shingrix vaccination]. Kohn, D., Wetzig, T.[2021]

Shingrix is a new vaccine designed to prevent herpes zoster, commonly known as shingles, which can cause painful rashes and complications.

Clinical trials have shown that Shingrix is highly effective in reducing the incidence of shingles in adults, particularly in older populations, making it a significant advancement in herpes zoster prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Shingrix: A New Herpes Zoster Vaccine. Maltz, F., Fidler, B.[2020]

Shingrix® is a highly effective recombinant zoster vaccine that significantly reduces the risk of herpes zoster (HZ) and postherpetic neuralgia (PHN) in adults aged 50 and older, with efficacy remaining strong even after 4 years.

While Shingrix® is associated with more side effects than a placebo, such as injection-site reactions and fatigue, these reactions are generally mild to moderate and transient, making it a well-tolerated option for preventing HZ and PHN.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant Zoster Vaccine (Shingrix®): A Review in Herpes Zoster. Syed, YY.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6590925/

Shingrix: A New Herpes Zoster Vaccine - PMC The overall vaccine efficacy in the pooled analysis was 91.3% (95% CI, 86.8–94.5%). Table 2. ZOE-70: Efficacy of HZ/su on Incidence of Herpes Zoster Versus ...

2. shingrixhcp.com shingrixhcp.com/home-ic/immunogenicity-data/human-immunodeficiency-virus/

Human Immunodeficiency Virus | SHINGRIX (Zoster ... Dosing in the HIV study was 3 doses at 0, 2, and 6 months; however, administration of the third dose of SHINGRIX is outside the approved dosing schedule for ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0264410X25010205

Herpes zoster reactivation in a cohort of people living with ... People living with HIV (PLWH) have a higher risk of herpes zoster (HZ) reactivation and postherpetic neuralgia (PHN) compared to general population.

4. academic.oup.com academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaf329/8171839

Effectiveness of the Adjuvanted Recombinant Zoster Vaccine ... Two doses of RZV were effective in preventing HZ and PHN in adults aged ≥50 years, with durable protection. These findings underscore the ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05580458

Study Details | NCT05580458 | Safety and Immunogenicity ... This phase 1/2 open-label study will evaluate the safety and immunogenicity of the Shingrix recombinant varicella zoster virus vaccine (RZV) in people with HIV ...

6. fda.gov fda.gov/files/vaccines%2C%20blood%20%26%20biologics/published/Package-Insert-SHINGRIX.pdf

Package Insert - SHINGRIX The risk of developing HZ, which increases with age and with immunosuppression due to disease and/or therapy, appears to be related to a decline in varicella ...

7. shingrixhcp.com shingrixhcp.com/home-ic/efficacy-safety/adverse-reactions/

Safety Profile | SHINGRIX (Zoster Vaccine Recombinant, ... Safety was evaluated in 6 studies in 5 different immunocompromised populations aged 18 years and older.

8. shingrixhcp.com shingrixhcp.com/home-ic/efficacy-safety/overview/

Efficacy & Safety Overview Discover the efficacy and safety data in immunocompromised patients aged 18 years and older. Learn about the incidence of shingles and more.

9. cdc.gov cdc.gov/vaccine-safety/vaccines/shingles-herpes.html

Shingles (Herpes Zoster) Vaccine Safety A closer look at the safety data​​ Both Shingrix and Zostavax shingles vaccines have been shown to be safe and well tolerated. Common side effects, such as ...