Ostrowsky J.T.Vestin N.C.Mehr A.J.Ulrich A.K.Bigalke L.Bresee J.S.Friede M.H.Gellin B.G.Klugman K.P.Nakakana U.N.Wang T.Y.Weller C.L.Osterholm M.T.Lackritz E.M.Moore K.A.Ampofo W.Belongia E.Cavaleri M.Cohen C.Cowling B.Cox R.J.Gupta S.Gust I.Hensley S.E.Isakova-Sivak I.Johansen K.Knobler S.Krammer F.Lim J.C.W.McCauley J.Pebody R.Pitisuttithum P.Rappuoli R.Rocca T.Schultz-Cherry S.Settembre E.C.Southern J.Subbarao K.Tam J.S.Venkayya R.Mahidol University2025-07-092025-07-092025-08-13Vaccine Vol.61 (2025)0264410Xhttps://repository.li.mahidol.ac.th/handle/20.500.14594/111145Influenza vaccines that provide more effective immunity to seasonal influenza as well as protection against a broad range of emerging influenza viruses with pandemic potential are needed to reduce the public-health burden of influenza and enhance pandemic preparedness. The Influenza Vaccines Research and Development (R&D) Roadmap (IVR) was published in 2021 to serve as a strategic planning tool to advance influenza vaccine R&D. Following IVR publication, a 3-year monitoring, evaluation, and adjustment (ME&A) program was implemented to assess progress in meeting the milestones outlined in the IVR. As of mid-May 2025, 16 (17%) of the 93 milestones had been accomplished or partially accomplished, with the majority (67; 72%) in various stages of progress. Of the 35 milestones designated high-priority, five (14%) had been accomplished or partially accomplished, 29 (83%) are in progress, and no progress was identified for one (3%). Key accomplishments include: establishing longitudinal cohort studies to characterize immune responses to influenza virus infection and vaccination by age over time and by vaccine product; creating a comprehensive landscape of innovative influenza vaccine technologies in preclinical and clinical development; advancing next-generation and broadly protective influenza vaccine candidates into clinical trials; identifying relevant lessons learned from accelerated SARS-CoV-2 vaccine development during the COVID-19 pandemic; and initiating development of a full value of improved influenza vaccine assessment (FVIVA) to inform investment and guide the eventual uptake of improved vaccines globally. Persistent challenges include clarifying immune mechanisms for generating durable and broadly protective immunity, enhancing understanding of immune imprinting and the role of mucosal immunity in preventing infection and transmission, identifying correlates of protection, and exploring regulatory options for broadly protective influenza vaccine licensure. The IVR ME&A program provides a basis for ongoing critical review of progress in influenza vaccine R&D to inform decision-making on research priorities and funding.Biochemistry, Genetics and Molecular BiologyMedicineImmunology and MicrobiologyVeterinaryAccomplishments and challenges in developing improved influenza vaccines: An evaluation of three years of progress toward the milestones of the influenza vaccines research and development roadmapReviewSCOPUS10.1016/j.vaccine.2025.1274312-s2.0-10500942739018732518