{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:11:53Z","timestamp":1760058713922,"version":"build-2065373602"},"reference-count":65,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T00:00:00Z","timestamp":1745539200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Mirror Biologics, Inc."},{"name":"independent clinical research organization (CRO)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Respiratory viral infections pose a significant health problem that disproportionately affects the elderly. With the aging worldwide population being less responsive to protective vaccines, there is an urgent need for strategies that can protect the elderly from community-acquired viral infections. Background\/Objectives: Allo-priming is a novel immunomodulatory vaccine concept using allogeneic, living, activated Th1 cells that are rejected by the host, creating anti-alloantigen Th1 immunity, increasing Th1 titers. Th1 cells orchestrate cellular immunity, and the age-related decline in Th1 cells contributes to weakened cellular immune response in the elderly, which correlates with poor responsiveness to vaccines and increased susceptibility to respiratory viral infections. Increased Th1 cell titers in the elderly were hypothesized to reverse immunosenescence and restore cellular immune function. Restoration of cellular immune function was predicted to restore broad respiratory viral protection through a heterologous immune mechanism. Methods: A phase I\/II, multi-center, open-label clinical trial was conducted in 40 healthy adults over 65 years of age to investigate the safety of allo-priming and the effects this vaccination strategy has on cellular immune function over time. Results: Allo-priming had a benign safety profile and significantly increased the titers of circulating Th1 cells. The increase in Th1 cells was shown to provide broad, self-amplifying respiratory viral protection over time in an ex vivo cytopathic effect assay without additional vaccinations and without any viral antigens included in the formulation, as well acting to increase neutralizing antibody titers in low-responding individuals previously vaccinated for COVID-19. Conclusions: These results provide support for an expanded clinical evaluation of this immunomodulatory vaccination strategy as a possible method to restore cellular immune competence to the elderly and provide broad heterologous immune protection from respiratory viral infections without the need for frequent vaccine re-formulations or booster shots (National Library of Medicine: NCT04441047).<\/jats:p>","DOI":"10.3390\/vaccines13050463","type":"journal-article","created":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T10:42:09Z","timestamp":1745577729000},"page":"463","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Allo-Priming Reverses Immunosenescence and May Restore Broad Respiratory Viral Protection and Vaccine Responsiveness to the Elderly: Results of a Phase I\/II Clinical Trial"],"prefix":"10.3390","volume":"13","author":[{"given":"Canhui","family":"Liu","sequence":"first","affiliation":[{"name":"Mirror Biologics, Inc., Wesley Chapel, FL 33544, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaochuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Mirror Biologics, Inc., Wesley Chapel, FL 33544, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge","family":"Paoli-Bruno","sequence":"additional","affiliation":[{"name":"Coral Research Clinical Corp, Miami, FL 33186, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Sikes","sequence":"additional","affiliation":[{"name":"Florida Medical Clinic Orlando Health, Zephyrhills, FL 33542, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alejandra V.","family":"Marin-Ruiz","sequence":"additional","affiliation":[{"name":"Model Research, Tampa, FL 33615, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"Thomas","sequence":"additional","affiliation":[{"name":"Delray Physician Care Center, Delray Beach, FL 33445, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan","family":"Shane","sequence":"additional","affiliation":[{"name":"Mirror Biologics, Inc., Wesley Chapel, FL 33544, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9342-9337","authenticated-orcid":false,"given":"Michael","family":"Har-Noy","sequence":"additional","affiliation":[{"name":"Mirror Biologics, Inc., Wesley Chapel, FL 33544, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e039887","DOI":"10.1136\/bmjopen-2020-039887","article-title":"Age differences in clinical features and outcomes in patients with COVID-19, Jiangsu, China: A retrospective, multicentre cohort study","volume":"10","author":"Luo","year":"2020","journal-title":"BMJ Open"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1055\/s-2007-976489","article-title":"Respiratory syncytial virus infection in adults","volume":"28","author":"Falsey","year":"2007","journal-title":"Semin. 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