Influenza Vaccines for Persons Who Are Immunocompromised: A Scoping Review of the Literature

Second-generation influenza vaccines include high-dose inactivated vaccine, recombinant vaccine, and MF-59 adjuvanted inactivated vaccine. In 2022, the US Advisory Committee on Immunization Practices issued a preferential recommendation for second-generation vaccines in adults aged ≥65 years. A substantial proportion of individuals aged <65 years who are immunocompromised may be insufficiently protected by first-generation standard-dose inactivated influenza vaccines. This scoping review assessed evidence on the immunogenicity, efficacy, effectiveness, and safety of influenza vaccines in immunocompromised populations to potentially inform public health decision making and identify research gaps for improved influenza control.

In May 2026, we searched MEDLINE for studies published since 2014 that reported on vaccine effectiveness, efficacy, and immune response to influenza vaccination in individuals who were immunocompromised. Outcomes related to immunogenicity, clinical protection, and safety were assessed for first- and second-generation vaccines.

Our search strategy identified 1239 articles, of which 112 met inclusion criteria. Among these, 69 focused on first-generation standard-dose influenza vaccines, 31 on second-generation vaccines, and 12 included both generations. Most studies (86%) reported immunogenicity data, while only 19% reported efficacy of effectiveness results. Few studies reported higher immunogenicity with second-generation vaccines and following a booster dose. Current evidence of second-generation influenza vaccine effectiveness was limited and inconsistent. No safety concerns were reported with first- and second-generation influenza vaccines among persons who were immunosuppressed.

We describe current evidence on influenza vaccine response, vaccine effectiveness, and vaccine safety in persons who are immunocompromised. The review highlights the lack of evidence supporting enhanced effectiveness of second-generation influenza vaccines in persons who are immunocompromised, although immunogenicity data and data from nonimmunocompromised populations support the potential benefits among persons aged <65 years who are immunocompromised.