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Immunogenicity of an AAV-Based COVID-19 Vaccine in Murine Models of Obesity and Aging
Authors:Dawid Maciorowski  Cheikh Diop  Urja Bhatt  Reynette Estelien  Dan Li  Ruchi Chauhan  Luk H. Vandenberghe  Nerea Zabaleta
Affiliation:1.Grousbeck Gene Therapy Center, Schepens Eye Research Institute, Mass Eye and Ear, Boston, MA 02114, USA; (D.M.); (C.D.); (U.B.); (R.E.); (D.L.); (R.C.);2.Department of Ophthalmology, Ocular Genomics Institute, Harvard Medical School, Boston, MA 02114, USA;3.The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA;4.Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA
Abstract:The SARS-CoV-2 pandemic has had a disastrous impact on global health. Although some vaccine candidates have been effective in combating SARS-CoV-2, logistical, economical, and sociological aspects still limit vaccine access globally. Recently, we reported on two room-temperature stable AAV-based COVID-19 vaccines that induced potent and protective immunogenicity following a single injection in murine and primate models. Obesity and old age are associated with increased mortality in COVID-19, as well as reduced immunogenicity and efficacy of vaccines. Here, we investigated the effectiveness of the AAVCOVID vaccine candidates in murine models of obesity and aging. Results demonstrate that obesity did not significantly alter the immunogenicity of either vaccine candidate. In aged mice, vaccine immunogenicity was impaired. These results suggest that AAV-based vaccines may have limitations in older populations and may be equally applicable in obese and non-obese populations.
Keywords:SARS-CoV-2   COVID-19   vaccine   genetic vaccine   adeno-associated virus   AAV   obesity   aging   animal model
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