Introduction and Context
The Infectious Diseases Society of America (IDSA) released updated guidance in 2025 that strengthens recommendations for influenza and respiratory syncytial virus (RSV) vaccination in people with weakened immune systems. The guidance, published online in JAMA (doi:10.1001/jama.2025.19738), reflects a focused evidence review of recent vaccine effectiveness and safety studies that enrolled immunocompromised participants. The panel reviewed 17 influenza studies and 5 RSV studies published after August 2023 and August 2024, respectively, and issued practical recommendations intended to reduce severe respiratory disease and deaths in a population at high risk of complications.
This update matters because immunocompromised people — including recipients of organ transplants, patients receiving cancer chemotherapy or biologic immunomodulators, and people with primary immunodeficiency or advanced HIV — have higher risks of severe influenza and RSV disease, prolonged viral shedding, and poorer vaccine responses. Newer vaccine formulations (for example, high-dose or adjuvanted influenza vaccines and recently licensed RSV immunizations for older adolescents and adults) plus accumulating safety data created an opportunity to clarify optimal vaccine choices and timing for this vulnerable group.
This article reviews the 2025 update of the Infectious Diseases Society of America (IDSA) recommendations regarding influenza and RSV vaccination for immunocompromised populations, providing a comprehensive evidence-based perspective for clinical application.
Study Design:
The guideline update is based on a systematic review of evidence published after August 2023, including recent high-quality randomized controlled trials (RCTs), large-scale prospective cohorts, and safety surveillance databases. It further incorporates expert consensus for areas where empirical evidence is limited. The recommendations specifically address subpopulations such as solid organ transplant recipients, patients receiving chemotherapy or biologics, those with primary immunodeficiency, and advanced HIV, with stratification by age and clinical context.
Level of Evidence:
The recommendations are supported by a hierarchy of evidence, led by RCTs and validated real-world data analyses, supplemented by expert opinion to strengthen areas with lower direct evidence. As such, the guideline achieves a high evidence grade, facilitating stronger and more operational recommendations for clinicians compared to previous editions based on fewer or less robust studies.
Key Findings:
Annual inactivated influenza vaccination is strongly recommended for virtually all immunocompromised individuals (≥6 months), with a clear preference for high-dose or adjuvanted formulations (e.g., high-dose Fluzone, Fluad).
RSV vaccination is advised for all immunocompromised adolescents and adults; pediatric indications are to be individualized according to risk and available data.
The use of live attenuated influenza vaccine (LAIV) is contraindicated in immunocompromised individuals, and close contacts of severely immunosuppressed people should also avoid LAIV to minimize risk of viral transmission.
“Cocooning” strategies—encouraging universal flu and RSV vaccination among household members and close contacts—are highlighted to provide indirect protection for the immunocompromised.
Co-administration with COVID-19 vaccines is deemed safe and operationally efficient, without the need for spacing doses.
Timing of vaccine administration should ideally precede initiation of immunosuppressive therapy, with adjustments when ongoing therapy cannot be postponed.
Data demonstrate that high-dose and adjuvanted vaccines confer better immunogenicity and clinical outcomes in immunocompromised hosts, with no major safety concerns reported.
Clinical Implications:
The 2025 IDSA update streamlines clinical pathways for high-risk patients and provides actionable guidance for optimizing individual and household protection. Its practical orientation (e.g., co-administration of vaccines, clear contraindications, family-based prevention) can help clinicians proactively screen, educate, and vaccinate vulnerable groups, effectively mitigating severe influenza and RSV morbidity and mortality.
Ongoing Clinical Issues:
Not all recommended vaccines (e.g., high-dose formulations, RSV vaccines) are universally available or affordable, with policy and supply challenges remaining, particularly outside the US.
There are limited direct data for some populations, such as immunocompromised children, necessitating shared decision-making and multidisciplinary coordination.
Heterogeneity of immune impairment, disease subtypes, and medication regimens still leaves important gaps in risk stratification and evidence tailoring; more direct comparative RCTs and large-scale implementation studies are warranted for these subgroups.
Future Research Directions:
Continued head-to-head RCTs and real-world effectiveness studies should clarify vaccine performance across various immunosuppressed populations and immunosuppression regimens. Research on durability of immunity and timing of booster administration, especially for RSV and emerging respiratory pathogens, is needed. Further work should address cost-effectiveness, safety in less-studied pediatric and rare disease cohorts, and best practices for broadening vaccine access and uptake.
In summary, this IDSA guideline update represents a significant advancement in the prevention of severe influenza and RSV infections among immunocompromised individuals, supporting stronger, simplified, and more comprehensive care and public health strategies. Successful translation into practice will depend on interdisciplinary cooperation, continued surveillance, and health policy alignment.