ACIP Evidence to Recommendations (EtR) Framework: High-Dose and Adjuvanted Influenza Vaccines for Solid Organ Transplant Recipients
Question: Should high-dose inactivated, adjuvanted inactivated, and/or recombinant influenza vaccines be recommended as an option for influenza vaccination of solid organ transplant recipients who are younger than the approved age indication?
Population: Solid organ transplant recipients aged ≥6 months
Interventions: High-dose (HD-IIV) (including use of multiple doses of standard-dose inactivated influenza vaccines[SD-IIVs]), MF59-djuvanted (aIIV), or recombinant (RIV) trivalent or quadrivalent influenza vaccines
Comparisons: Single intramuscular dose of trivalent or quadrivalent unadjuvanted standard dose influenza vaccines
Outcomes:
Benefits:
- Medically-attended influenza (Critical)
- Influenza-associated hospitalization (Critical)
- Laboratory-confirmed influenza—immunogenicity data acceptable (Important)
Harms:
- Transplant rejection or graft failure (Critical)
- Neuroinflammatory conditions , e.g. GBS, ADEM (Critical)
- Other immune-related adverse events, including new onset or exacerbation of an autoimmune condition (Critical)
Background: Solid organ transplant recipients generally require lifelong immunosuppressive medications in order to maintain graft function, and are potentially at increased risk of severe and complicated influenza illness (1, 2). Higher-dose and adjuvanted influenza vaccine strategies have been studied in this population as interventions which might promote a stronger immune response (3-9). The American Society for Transplantation (AST) states that high-dose or boosted influenza vaccine dosing might be preferable post-transplant (10). However, currently available high-dose and adjuvanted inactivated influenza vaccines are approved only for persons aged ≥65 years in the United States (11, 12).
Public Health Importance
Criteria | Work Group Judgements | Evidence | Additional Information |
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Is the problem of public health importance? | Yes |
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Benefits and Harms
Criteria | Work Group Judgements | Evidence | Additional Information |
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How substantial are the desirable anticipated effects? | Don't Know |
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How substantial are the undesirable anticipated effects? | Minimal |
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Do desirable effects outweigh undesirable effects? | Favors Intervention |
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What is the overall certainty of the evidence of effects? | Overall GRADE Evidence Certainty: Benefits: Low Harms: Moderate |
Values
Criteria | Work Group Judgements | Evidence | Additional Information |
---|---|---|---|
Does the target population feel that the desirable effects are large relative to undesirable effects? | Probably Yes |
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Is there important uncertainty about or variability in how much people value the main outcomes? | Probably Not Important Uncertainty or Variability |
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Acceptability
Criteria | Work Group Judgements | Evidence | Additional Information |
---|---|---|---|
Is the intervention acceptable to key stakeholders? | Probably Yes |
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Resource Use
Criteria | Work Group Judgements | Evidence | Additional Information |
---|---|---|---|
Is the intervention a reasonable and efficient allocation of resources? | Probably Yes |
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Equity
Criteria | Work Group Judgements | Evidence | Additional Information |
---|---|---|---|
What would be the impact on health equity? | Probably increased |
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Feasibility
Criteria | Work Group Judgements | Evidence | Additional Information |
---|---|---|---|
Is the intervention feasible to implement? | Probably Yes |
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A lesser proportion of WG members indicated “yes”. |
Balance of Consequences:
The majority of the Work Group members responded that desirable consequences probably outweigh undesirable consequences in most settings. A smaller proportion responded that there is insufficient evidence, that desirable consequences clearly outweigh undesirable consequences in most settings, or that the evidence is closely balanced or uncertain.
Work Group Judgement of Sufficiency of Information:
The Work Group feels there is sufficient evidence to move forward with a recommendation.
ACIP Recommendation:
ACIP recommends high-dose inactivated (HD-IIV3) and adjuvanted inactivated (aIIV3) influenza vaccines as acceptable options for influenza vaccination of solid organ transplant recipients aged 18 through 64 years who are receiving immunosuppressive medication regimens, without a preference over other age-appropriate IIV3s or RIV3.
References
- Mombelli M, Kampouri E, Manuel O. Influenza in solid organ transplant recipients: epidemiology, management, and outcomes. Expert Rev Anti Infect Ther. 2020 Feb;18(2):103-12.
- Kumar D, Ferreira VH, Blumberg E, Silveira F, Cordero E, Perez-Romero P, et al. A 5-Year Prospective Multicenter Evaluation of Influenza Infection in Transplant Recipients. Clin Infect Dis. 2018 Oct 15;67(9):1322-9.
- Mombelli M, Neofytos D, Huynh-Do U, Sanchez-Cespedes J, Stampf S, Golshayan D, et al. Immunogenicity of High-Dose Versus MF59-Adjuvanted Versus Standard Influenza Vaccine in Solid Organ Transplant Recipients: The Swiss/Spanish Trial in Solid Organ Transplantation on Prevention of Influenza (STOP-FLU Trial). Clin Infect Dis. 2024 Jan 25;78(1):48-56.
- Mombelli M, Rettby N, Perreau M, Pascual M, Pantaleo G, Manuel O. Immunogenicity and safety of double versus standard dose of the seasonal influenza vaccine in solid-organ transplant recipients: A randomized controlled trial. Vaccine. 2018 Oct 1;36(41):6163-9.
- Natori Y, Shiotsuka M, Slomovic J, Hoschler K, Ferreira V, Ashton P, et al. A Double-Blind, Randomized Trial of High-Dose vs Standard-Dose Influenza Vaccine in Adult Solid-Organ Transplant Recipients. Clin Infect Dis. 2018 May 17;66(11):1698-704.
- Kumar D, Campbell P, Hoschler K, Hidalgo L, Al-Dabbagh M, Wilson L, Humar A. Randomized Controlled Trial of Adjuvanted Versus Nonadjuvanted Influenza Vaccine in Kidney Transplant Recipients. Transplantation. 2016 Mar;100(3):662-9.
- Magnani G, Falchetti E, Pollini G, Reggiani LB, Grigioni F, Coccolo F, et al. Safety and efficacy of two types of influenza vaccination in heart transplant recipients: a prospective randomised controlled study. J Heart Lung Transplant. 2005 May;24(5):588-92.
- Odongo FCA, Braga PE, Palacios R, Miraglia JL, Sartori AMC, Ibrahim KY, et al. An Open-label Randomized Controlled Parallel-group Pilot Study Comparing the Immunogenicity of a Standard-, Double-, and Booster-dose Regimens of the 2014 Seasonal Trivalent Inactivated Influenza Vaccine in Kidney Transplant Recipients. Transplantation. 2022 Jan 1;106(1):210-20.
- Pollok M, Geiger H, Floege J, Paschke R, Abendroth D, Bienzle U, et al. Increased immunogenicity with an MF59-adjuvanted influenza vaccine (FLUAD(R)) compared with a conventional subunit vaccine (Agrippal(R)) in renal transplant recipients. International Congress Series. 2004;1263:453-6.
- Danziger-Isakov L, Kumar D, et al. Vaccination of solid organ transplant candidates and recipients: Guidelines from the American society of transplantation infectious diseases community of practice. Clin Transplant. 2019 Sep;33(9):e13563.
- Fluzone High-Dose [Package Insert]. Swiftwater, PA: Sanofi Pasteur; 2024.
- Fluad [Package Insert]. Holly Springs, NC: Seqirus; 2024.
- Organ Procurment and Transplantation Network/Scientific Registry of Transplant Reicipients (OPTN/SRTR). 2020 Annual Data Report.
- Centers for Medicare and Medicaid Services. Influenza vaccine pricing, 2023-24.