ACIP Evidence to Recommendations Framework for Use of Recombinant Zoster Vaccine in Immunocompromised Adults Aged ≥19 Years

About

The Evidence to Recommendations (EtR) frameworks describe information considered in moving from evidence to ACIP vaccine recommendations.

Summary

Question: Should adults aged ≥19 years who are or will be immunodeficient or immunosuppressed because of disease or therapy be recommended to receive two doses of recombinant zoster vaccine for the prevention of herpes zoster and related complications?

Population: Immunocompromised adults aged ≥19 years

Intervention: Recombinant zoster vaccine (RZV), 2 doses at least 4 weeks apart*

Comparison: No vaccine

Outcomes: Herpes zoster, Serious adverse events, Postherpetic neuralgia, Herpes zoster-related hospitalization, Immune-mediated disease, Graft-versus-host-disease, Graft rejection, Reactogenicity (grade 3)

*The second RZV dose should typically be given 2–6 months after the first; for persons who are or will be immunodeficient or immunosuppressed and who would benefit from a shorter vaccination schedule, the second dose can be administered 1–2 months after the first.

Background

Herpes zoster is a painful, cutaneous eruption, usually involving one to three adjacent dermatomes,† resulting from reactivation of latent varicella-zoster virus. Herpes zoster rates increase with age, with annual incidence rates ranging from ~2 to 9 per 1,000 persons.1 The likelihood of developing postherpetic neuralgia (PHN) also increases with age. The risk for herpes zoster and related complications is generally higher in immunocompromised compared with immunocompetent adults, although there is heterogeneity within and across immunocompromised groups.23 The risk for herpes zoster among younger adults with certain immunocompromising conditions can be comparable to or higher than that in the general adult population aged >50 years.23 Because immunosuppression and immunodeficiency were contraindications for the previously available vaccine, zoster vaccine live (ZVL),§ and RZV was originally recommended for immunocompetent adults aged ≥50 years, there has been an unmet need for vaccination against herpes zoster in immunocompromised adults.

In October 2017, RZV (Shingrix) was licensed in the United States for prevention of herpes zoster for adults aged ≥50 years by the Food and Drug Administration (FDA) and recommended for immunocompetent adults ≥50 years by the Advisory Committee on Immunization Practices (ACIP).4 In January 2018, the recommendation became official CDC policy and vaccine uptake began in earnest in March 2018. During December 2017–October 2021, the ACIP Herpes Zoster Work Group (HZWG) participated in monthly or bimonthly teleconferences to review herpes zoster epidemiology and evidence for the efficacy and safety of RZV in immunocompromised adults. These topics were discussed during four ACIP meetings in 2021. On August 25, 2020, the European Medicines Agency approved an expanded indication for RZV; therefore, RZV is approved in the European Union for prevention of herpes zoster and PHN in adults aged ≥50 years, and adults aged ≥18 years at increased risk for herpes zoster.5 On July 23, 2021, the FDA expanded the indication for RZV to include adults aged ≥18 years who are or will be at increased risk for herpes zoster because of immunodeficiency or immunosuppression caused by known disease or therapy.6 The Shingrix package insert was also updated to note a vaccination schedule of two intramuscular doses 1–2 months apart for use in persons who are or will be immunodeficient or immunosuppressed and who would benefit from a shorter vaccination schedule.

Additional background information supporting the ACIP recommendations on the use of RZV can be found in the relevant publication of the recommendation referenced on the ACIP website.

† A dermatome is a cutaneous area of skin supplied by one spinal nerve.

§ Zoster vaccine live is no longer available for use in the United States, as of November 18, 2020.

Problem

References in this table:237891011121314

Criteria Work Group Judgments Evidence Additional Information
Is the problem of public health importance? Yes Millions of persons in the United States are immunocompromised. In the 2013 National Health Interview Survey (NHIS), approximately 7 million adults self-reported immune suppression.[7] The prevalence of self-reported immune suppression was 1.6% among persons 18–39 years and 2.3% among those 40–49 years, with prevalence ranging from 2.5% to 4.4% for older age groups. There are a total of approximately 3 million  hematopoietic cell transplant (HCT) recipients, patients with hematologic malignancies, renal or other solid organ transplant (SOT) recipients, patients with solid tumor malignancies, and people living with HIV.[8], [9], [10], [11], [12] In addition to these groups, there are approximately 22 million with one of more than 80 diverse autoimmune (AI) and inflammatory (INF) conditions, such as systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel disease (IBD).[13] These patients often have underlying immune defects, but generally are not considered frankly immunocompromised unless they are on immunosuppressing treatments. Importantly, an increasing proportion of immunocompromised patients are likely to be treated with immunosuppressive therapies. Age-specific prevalence of immunocompromise is highly variable by condition.
In a systematic literature review regarding the risk for herpes zoster in immunocompromised  groups (HCT recipients, patients with hematologic malignancies, SOT recipients, patients with solid tumor malignancies, people living with HIV), it was noted that the median herpes zoster incidence estimates for these groups exceeded those reported for immunocompetent adults >50 years.[2] The incidence rate of herpes zoster ranged between 9 and 95 per 1,000 person-years, with variation within and between groups based on underlying disease and therapies received. Herpes zoster complications, including PHN, and severe disease were also increased in immunocompromised  populations.
In a study of select AI/INF conditions, risk for herpes zoster was about 2- to 4-fold higher in patients with AI conditions than in healthy persons.[3] Another recent study identified similar results, with an approximately 1.5-fold higher risk for herpes zoster for unvaccinated Medicare beneficiaries with AI conditions versus those who were not immunocompromised.[14]
 Immunocompromising conditions and immunosuppressive therapies are very heterogenous.
The risk for herpes zoster and related complications are generally higher among patients with immunocompromising conditions; however, there is variability within and across groups and among individuals over time depending on disease course or immunosuppressive therapies.
Given this heterogeneity, it is important to consider a broad recommendation with provider guidance for immunocompromised populations.

Benefits and Harms

References in this table:15

Criteria Work Group Judgments Research Evidence [15] Additional Information
How substantial are the desirable anticipated effects? Large Risk for herpes zoster, PHN, and hospitalizations attributed to herpes zoster were reduced among persons who received two doses of RZV vs. placebo. Estimates of vaccine efficacy (VE) came from three studies, with VE of 68.2% (95% Confidence Interval [CI]: 55.6%, 77.5%) for autologous hematopoietic cell transplant recipients, and 87.2% (44.3%–98.6%) and 90.5% (73.5%–97.5%) in post hoc efficacy analyses for patients with hematologic malignancies and potential immune-mediated diseases (pIMDs), respectively (GRADE Table 3a). Subgroup analyses by age revealed similar efficacy.
Non-randomized studies examining patients with AI and immunocompromising conditions or IBD reported VE estimates of 68% (95% CI: 62.3%, 72.8%) for those with AI conditions and 64.1% (95% CI: 57.2%, 69.8%) for those with immunocompromising conditions. For IBD patients over age 60, hazard ratios were reported of 0.41 (95% CI: 0.19, 0.87) for non-steroid users and 0.34 (95% CI: 0.05, 2.44) for steroid users.
Immunogenicity data from six randomized trials showed humoral vaccine response rates ranging from 65.4% to 96.2% and cell-mediated responses ranging from 50% to 93%, compared with 0% to 4.2% and 0% to 16.7% for humoral and cell-mediated response among placebo recipients, respectively (Grade Table 3b).
Only one study provided data on PHN and herpes zoster-related hospitalizations in autologous HCT recipients, showing a VE of 89% (95% CI: 22%, 100%) for prevention of PHN (GRADE Table 3d) and 85% (95% CI: 32%, 97%) for prevention of herpes zoster-related hospitalization (GRADE Table 3e).
 Clinical trials were conducted in autologous HCT recipients aged ≥18 years, patients living with HIV aged ≥18 years, patients with hematologic malignancies aged ≥18 years, and persons with pIMDs aged ≥50 years; cohort analyses were performed for Medicare beneficiaries with AI or immunocompromising conditions, as well as VA health system patients with IBD.
How substantial are the undesirable anticipated effects? Small Serious adverse events (SAEs) were common in both vaccine and placebo groups, and the risk was balanced across groups (Grade Table 3c). Overall, risk ratios for SAEs ranged from 0.79 (95% CI: 0.60, 1.05) to 1.99 (95% CI: 0.42, 9.44). SAEs attributed to vaccination were rare, ranging from 0% to 1.6% among RZV recipients and 0% to 0.76% among placebo recipients.
Non-specified IMDs were reported by 0% to 1.4% of RZV recipients, new onset IMDs were reported by 1.6% to 3.0% of RZV recipients, and exacerbations of existing IMDs were reported by 2.8% of RZV recipients. Overall, similar rates of IMDs were reported in the placebo group, with risk ratios ranging from 0 to 1.63 for non-specified, from 0.68 to 2.0 for new-onset, and 0.98 (95% CI: 0.58, 1.65) for exacerbations of IMDs (GRADE Table 3f).
For graft-versus-host-disease, one randomized trial found 3/19 (15.8%) RZV recipients experienced graft-versus-host-disease, compared to 4/21 (19.0%) placebo recipients, for a calculated risk ratio of 0.83 (95% CI: 0.21, 3.24) (GRADE Table 3g). For graft rejection, 4 episodes of rejection were reported in 132 RZV recipients (3.0%) in a single trial, compared with 7/132 (5.3%) in placebo recipients, for a calculated risk ratio of 0.57 (95% CI: 0.17, 1.91) (GRADE Table 3h).
Grade 3 reactogenicity was increased among persons who received at least 2 doses of RZV rather than placebo (GRADE Table 3i). Solicited local and systemic reactions within 7 days after vaccination were frequent and mostly mild to moderate. Grade 3 local reactions were reported by 10.7% to 14.2% of RZV recipients, with the most frequent reported symptom being injection-site pain. Grade 3 solicited systemic reactions were reported by 9.9% to 22.3% of RZV recipients, and 6.0% to 15.5% of placebo recipients, with the most commonly reported symptoms being fatigue and myalgia.
 Safety data showed an acceptable safety profile across a range of immunocompromised  groups.

Post marketing surveillance will be critical to detect any rare SAEs which were not identified in the clinical trials.
Do the desirable effects outweigh the undesirable effects? Favors intervention The ACIP HZWG concluded that the desirable effects of two doses of RZV in immunocompromised adults outweigh the undesirable effects.
What is the overall certainty of this evidence for the critical outcomes? Effectiveness of the intervention is Level 2 (Moderate)

Safety of the intervention is Level 2 (Moderate)

 For critical outcomes, the certainty of evidence was moderate for prevention of herpes zoster and moderate for SAEs. For important outcomes, the certainty of evidence was low for prevention of PHN, prevention of herpes zoster-related hospitalizations, and graft rejection; very low for IMD and graft-versus-host-disease; and moderate for reactogenicity (grade 3).

Values

References in this table:14161718

Criteria Work Group Judgments Research Evidence Additional Information
Does the target population feel that the desirable effects are large relative to undesirable effects? Probably yes There are limited data on knowledge, attitudes, and practices among immunocompromised  patients regarding potential use of RZV for prevention of herpes zoster and related complications.
In general, herpes zoster vaccination (including ZVL and RZV) is increasing (from 6.7% in 2008 to 34.5% in 2018[16] to 41.2% in 2019[17]) and RZV series completion rates are high; among Medicare enrollees from 2016–2019, 67% received 2 doses of RZV,[14] and IQVIA data showed 70% series completion after 6 months and 80% after 12 months.[18]
Immunocompromised patients recognize the increased risk for herpes zoster and many received RZV prior to an ACIP recommendation, as noted in a large study of Medicare data where nearly a million patients met the study definitions of autoimmune and immunocompromising conditions and received RZV.[14]
Concerns related to grade 3 reactions may discourage some immunocompromised patients from getting RZV.
 The ACIP HZWG placed high value on prevention of herpes zoster and related complications in immunocompromised  adults. Given the high incidence of herpes zoster and related complications in these patients, it is anticipated that more immunocompromised patients would pursue vaccination with RZV if recommended by ACIP and their provider.
Is there important uncertainty about or variability in how much people value the main outcomes? Probably not important uncertainty or variability The ACIP HZWG agreed that there is probably not important uncertainty or variability in how much immunocompromised adults value the main outcomes.

Acceptability

References in this table:19

Criteria Work Group Judgments Research Evidence Additional Information
Is the intervention acceptable to key stakeholders? Yes A 2020 University of Colorado Denver (UCD) survey of primary care physicians serving adults assessed practices, attitudes, and knowledge about RZV, barriers to recommending RZV, and the likelihood of recommending RZV to patients with various immunocompromising conditions.[19] Physicians in existing Vaccine Policy Collaborative Initiative sentinel networks were surveyed, including family physicians and general internists.
Regarding physician strength of recommendation for RZV consistent with ACIP recommendations at the time of the survey: 96%, 79%, and 70% of physicians recommended RZV for healthy adults ≥50 years, adults ≥50 years anticipating having a bone marrow or SOT who are not yet on immunosuppressive therapy, and adults ≥50 years on low dose methotrexate, respectively. Regarding physician strength of recommendation for RZV among patients not included in ACIP recommendations at the time of the survey: 67% of physicians recommended RZV to adults ≥50 years with HIV (CD4 count >200), 56% recommended RZV to adults ≥50 years on recombinant human immune mediator or modulator therapy, 48% recommended RZV to adults ≥50 years on chemotherapy, 42% recommended RZV to adults ≥50 years receiving immunosuppressive therapy for a bone marrow or SOT, and 31% recommended RZV to adults 18–49 years with an immunocompromising condition. Of note, 27% to 42% of respondents noted they deferred to a subspecialist for these immunocompromised populations 50 years and older.
Among physicians who had not recommended RZV to immunocompromised patients, the likelihood of recommending RZV to a range of immunocompromised patients 18 years of age and older was very likely for 40% to 48% of respondents and somewhat likely for 23% to 33% of respondents. A substantial minority would be unlikely to recommend RZV to various immunocompromised patients even if it were licensed, recommended, and covered by insurance for them (without input from a subspecialist).
These results highlight the importance of provider guidance for vaccination of immunocompromised patients.
 Given highly specialized care and increased herpes zoster risk among immunocompromised  patients, the ACIP HZWG noted that vaccination is favored if there are no safety concerns. Additional safety data is a research need; however, the work group considered currently available evidence acceptable.

Many specialty organizations are already recommending RZV for immunocompromised adults.

The ACIP HZWG anticipates that acceptability of RZV vaccination in immunocompromised adults would increase with FDA approval and ACIP recommendation.

Resource Use

References in this table:20

Criteria Work Group Judgments Research Evidence Additional Information
Is the intervention a reasonable and efficient allocation of resources? Yes Two studies assessed the economic efficiency of vaccinating immunocompromised adults 19 to 49 years of age against herpes zoster in the U.S.[20] Both studies compared vaccination with RZV to no vaccination. Both studies focused on HCT recipients as the base case, where the vaccination strategy was estimated to be cost-saving when compared to the no vaccination strategy.
Both models included additional scenarios that focused on persons with other immunocompromising conditions, including patients with hematologic malignancies, SOT recipients, patients living with HIV, patients with breast cancer, and patients with AI and INF conditions. Most of these scenarios found that the vaccination strategy costs per quality-adjusted life-year (QALY) gained ranged from being cost-saving to $99,000. In the CDC model scenario that focused on AI/INF conditions, the cost per QALY gained was estimated to be $208,000.
 In the base case, looking at HCT recipients, the economic value of RZV was cost-saving. In one model, vaccination reduced costs by 11% and increased QALYs by 6%. The cost-saving estimates among HCT recipients were influenced by relatively high herpes zoster incidence and high costs of herpes zoster-related health care, and reasonable VE among this patient group.
For scenarios focused on other immunocompromised patient groups, such as patients living with HIV ($33,000 to $79,000 per QALY) or patients with AI/INF conditions ($208,000 per QALY), the economic value of RZV vaccination was less favorable relative to HCT recipients given lower risk for herpes zoster, herpes zoster-related outcomes, and lower health care costs. Patients with AI/INF conditions had the least favorable estimates of economic value for RZV use, mainly due to the underlying risk for herpes zoster being relatively lower for this group.
Considering results across the base case and scenarios from both models, the ACIP HZWG determined the estimated economic values to be generally favorable. In addition, given the highly specialized care and resources typically invested for the base case and other immunocompromised groups, the work group did not consider cost-effectiveness assessments to be a main driver for overall decision-making.

Equity

References in this table:1721

Criteria Work Group Judgments Research Evidence Additional Information
What would be the impact on health equity? Probably increased The NHIS captures herpes zoster vaccination data, including data for ZVL and RZV.
Overall, in 2018, herpes zoster vaccination coverage among adults aged ≥50 years and ≥60 years was 24.1% and 34.5%, respectively.[21] White adults aged ≥50 years and ≥60 years had higher coverage (with 28.0% and 38.6%, respectively) compared with Black adults (12.4% and 18.8%, respectively), Hispanic adults (12.2% and 19.5%, respectively), and Asian adults (19.6% and 29.1%, respectively).
In an analysis using 2010–2019 NHIS data, in general, race/ethnicity, household income, education level, and health insurance type were significantly associated with receipt of herpes zoster vaccinations among adults aged ≥65 years.[17]
 The ACIP HZWG anticipates an ACIP recommendation would increase RZV access overall, since a recommendation increases the scope of the population eligible to be vaccinated and ensures coverage under the Affordable Care Act.
However, there will likely still be challenges with uptake, given the noted race/ethnicity, household income, education level, and insurance disparities. Variability in health insurance coverage and lack of insurance may result in out-of-pocket costs for some patients.
It will be important to continue monitoring RZV vaccination through the NHIS, including stratifying by health status and race/ethnicity. The work group also noted that equity could potentially be monitored at the local level during implementation.

Feasibility

References in this table:19

Criteria Work Group Judgments Research Evidence Additional Information
Is the intervention feasible to implement? Yes RZV is a refrigerator-stable, two-dose vaccine that can be co-administered with other adult vaccinations.
The 2020 UCD survey of primary care physicians regarding RZV assessed physician stocking and referring patterns: 47% of respondents both stocked RZV and referred patients for vaccination, 42% only referred patients to receive RZV, 7% percent only stocked RZV, and 4% did not stock or refer patients to receive RZV.[19] Of the 89% of physicians who referred patients to receive RZV at a location outside of their practice, 80% often/always referred to a pharmacy. Respondents indicated it was easier to refer and identified cost, inadequate reimbursement, and not being able to bill Medicare Part D as barriers to stocking the vaccine.
Pharmacies have continued to expand vaccination programs, especially for adults, and already are a major provider of RZV. Per the manufacturer, approximately 60%–65% of RZV is distributed to/administered in pharmacies. It is anticipated that identification of immunocompromised patients (for example, based on immunosuppressive medications, self-reported immunosuppression), standing orders, and that some pharmacies may be out of network (which could result in out-of-pocket costs for patients) will be concerns in the pharmacy setting.
 The U.S. health care system has experience delivering RZV to immunocompetent adults aged ≥50 years; however, various systemic factors continue to challenge the adult vaccination program in the U.S. (e.g., complicated reimbursement, lower prioritization of adult vaccines, fragmentation of care).
Identification of immunocompromised patients eligible for RZV in multiple settings (e.g., provider offices, pharmacies), particularly those 19 to 49 years of age, may be challenging; this highlights the need for provider and patient education materials and clinical decision support. Of note, the majority of jurisdictions have lifelong immunization information systems (IISs), which can receive adult immunization information. However, many do not receive health status information, therefore it is  anticipated that this will increase reliance on other systems (such as electronic health records) for decision support.
The ACIP HZWG noted that decision support guidance would be helpful. Further, it will be important to promote best practices and encourage providers to upload and update RZV vaccination information in jurisdiction IISs. Resources are available at Immunization Information Systems (IIS) | CDC.

Balance of Consequences

Desirable consequences clearly outweigh undesirable consequences in most settings.

Is there sufficient information to move forward with a recommendation? Yes.

ACIP recommends the intervention

Draft recommendation

Two doses of recombinant zoster vaccine are recommended for the prevention of herpes zoster and related complications in adults aged ≥19 years who are or will be immunodeficient or immunosuppressed because of disease or therapy.

Additional considerations

Monitoring RZV use in immunocompromised adults is particularly important given the heterogeneity of herpes zoster risk within and across immunocompromised groups and the novel adjuvant and high rates of reactogenicity of the vaccine. Limited data for outcomes deemed important by the ACIP HZWG (e.g., possible graft rejection, graft-versus-host-disease, immune-mediated disease) highlight the need for additional research.

A strong majority of the ACIP HZWG voted to recommend the intervention; a minority opinion was noted in favor of shared clinical decision-making, based on the following points:

  • The 1) heterogeneity of the immunocompromised populations under consideration and 2) variability in the risk for herpes zoster and related complications within and across these immunocompromised groups require more nuanced clinical judgment than a recommendation for routine vaccination.
  • The RZV clinical trials in immunocompromised adults included a small subset of immunocompromised categories, and the vaccine was administered at a tightly-defined time with respect to onset of immunocompromise (as compared to the work group’s recommendation to administer RZV well before or well after the onset of immunocompromise), which further highlights the need for nuanced clinical judgment.
  • Persons who have neither experienced varicella nor received varicella vaccine are not at risk for herpes zoster, and children and adolescents who have received live-attenuated varicella vaccines are at lower risk for herpes zoster than are those who experienced varicella.
    • Persons who have neither experienced varicella nor received varicella vaccines have not been included in RZV clinical trials and the safety of the vaccine in these groups is unknown.
    • Given the implementation of the universal varicella vaccination program in the U.S. in 1995, the majority of adults under 30 years of age have been vaccinated for varicella and the minority have experienced varicella; the benefits and costs of RZV will need ongoing review given the changing epidemiology of herpes zoster resulting from universal varicella vaccination.

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  1. Unpublished data, CDC; Updated from Harpaz R, Leung JW. The epidemiology of herpes zoster in the United States during the era of varicella and herpes zoster vaccines: changing patterns among older adults. Clin Infect Dis 2019;69:341–4. https://doi.org/10.1093/cid/ciy953
  2. McKay SL, Guo A, Pergam SA, Dooling K. Herpes zoster risk in immunocompromised adults in the United States: a systematic review. Clin Infect Dis 2020;71:e125–e134. https://doi.org/10.1093/cid/ciz1090
  3. Yun H, Yang S, Chen L, et al. Risk of herpes zoster in autoimmune and inflammatory diseases: implications for vaccination. Arthritis Rheumatol 2016;68:2328–37. https://doi.org/10.1002/art.39670
  4. Dooling KL, Guo A, Patel M, et al. Recommendations of the Advisory Committee on Immunization Practices for use of herpes zoster vaccines. MMWR Morb Mortal Wkly Rep 2018;67:103–8. http://dx.doi.org/10.15585/mmwr.mm6703a5
  5. European Medicines Agency. Committee for Medicinal Products for Human Use (CHMP) extension of indication variation assessment report. 2020. Available at: https://www.ema.europa.eu/en/documents/variation-report/shingrix-h-c-4336-ii-0022-epar-assessment-report-variation_en.pdf
  6. Food and Drug Administration. Shingrix [package insert], revised: 07/2021. Silver Spring, MD: US Department of Health and Human Services, Food and Drug Administration; 2021. https://www.fda.gov/media/108597/download
  7. Harpaz R, Dahl RM, Dooling KL. Prevalence of immunosuppression among US adults, 2013. JAMA 2016;316:2547–8.
  8. D’Souza A, Fretham C. Current uses and outcomes of hematopoietic cell transplantation (HCT): CIBMTR Summary Slides, 2018. Available at https://www.cibmtr.org
  9. American Cancer Society, https://cancerstatisticscenter.cancer.org; 2019 incidence estimates.
  10. United Network for Organ Sharing, https://unos.org/data/transplant-trends/#transplants_by_organ_type+year; 2018, Renal= Kidney + Kidney/Pancreas, Solid organ = all listed.
  11. Halpern MT, Yabroff KR, Cancer Invest, 2008, 26(6):647–51; Derived from Halpern and Yabroff 2000–2004 data on chemo/radiotherapy among all patients with cancers, adjusted based on proportion of all cancers in 2007 due to solid organ cancers, further adjusted by projections that solid cancers increased by 20% between 2007 and 2018 (data from American Cancer Society website).
  12. CDC, www.cdc.gov/hiv/statistics/overview/ataglance.html; 2017 incidence, 2016 prevalence of diagnosed HIV infections.
  13. Derived from Hayter SM. Autoimmun Rev. 2012 Aug;11(10):754–65 (prevalence 4.5% for all conditions excluding psoriasis) and Rachakonda TD. J Am Acad Dermatol 2014 Mar;70(3):512–6 (prevalence of 3.2% for psoriasis alone), applied to projected adult US population in 2020 (US Census: 289.6 million).
  14. Izurieta HS, Wu X, Forshee R, et al. Recombinant zoster vaccine (Shingrix): real-world effectiveness in the first 2 years post-licensure. Clin Infect Dis 2021;73:941–8. https://doi.org/10.1093/cid/ciab125
  15. https://wcms-wp.cdc.gov/acip/grade-evidence-tables-recommendations-in-mmwr/grading-recommendations-recombinant-zoster-immunocompromised.html
  16. Terlizzi EP and Black LI. Shingles vaccination among adults aged 60 and over: United States, 2018. NCHS Data Brief, No. 370, July 2020.
  17. Kawai K and Kawai AT. Racial/ethnic and socioeconomic disparities in adult vaccination coverage. Am J Prev Med 2021;000(000):1–9. https://doi.org/10.1016/j.amepre.2021.03.023
  18. Patterson BJ, Chen CC, McGuiness CB, et al. Early examination of real-world uptake and second-dose completion of recombinant zoster vaccine in the United States from October 2017 to September 2019. Hum Vaccin Immunother 2021 Aug 3;17:2482–87. https://doi.org/10.1080/21645515.2021.1879579
  19. Advisory Committee on Immunization Practices. ACIP meeting information. Atlanta, GA: US Department of Health and Human Services, CDC; October 20, 2021. https://wcms-wp.cdc.gov/acip/acip-meetings/index.html
  20. Advisory Committee on Immunization Practices. ACIP meeting information. Atlanta, GA: US Department of Health and Human Services, CDC; September 29, 2021. https://wcms-wp.cdc.gov/acip/acip-meetings/index.html
  21. Lu P, Hung M, Srivastav A, et al. Surveillance of vaccination coverage among adult populations — United States, 2018. MMWR Surveill Summ 2021;70(No. SS-3):1–26. http://dx.doi.org/10.15585/mmwr.ss7003a1