Durable immunogenicity, adaptation to emerging variants, and low-dose efficacy of an AAV-based COVID-19 vaccine platform in macaques.

The COVID-19 pandemic continues to have devastating consequences on health and economy, even after the approval of safe and effective vaccines. Waning immunity, the emergence of variants of concern, breakthrough infections, and lack of global vaccine access and acceptance perpetuate the epidemic. Here, we demonstrate that a single injection of an adenoassociated virus (AAV)-based COVID-19 vaccine elicits at least 17-month-long neutralizing antibody responses in non-human primates at levels that were previously shown to protect from viral challenge. To improve the scalability of this durable vaccine candidate, we further optimized the vector design for greater potency at a reduced dose in mice and non-human primates. Finally, we show that the platform can be rapidly adapted to other variants of concern to robustly maintain immunogenicity and protect from challenge. In summary, we demonstrate this class of AAV can provide durable immunogenicity, provide protection at dose that is low and scalable, and be adapted readily to novel emerging vaccine antigens thus may provide a potent tool in the ongoing fight against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).
Competing Interests: Declaration of interests J.M.W. is a paid advisor to and holds equity in Scout Bio and Passage Bio; he holds equity in Surmount Bio; he also has sponsored research agreements with Amicus Therapeutics, Biogen, Elaaj Bio, Janssen, Moderna, Passage Bio, Regeneron, Scout Bio, Surmount Bio, and Ultragenyx, which are licensees of Penn technology. L.H.V. and J.M.W. are inventors on patents that have been licensed to various biopharmaceutical companies and for which they may receive payments. L.H.V. is a paid advisor to Novartis, Akouos, and Affinia Therapeutics and serves on the Board of Directors of Affinia, Addgene, and Odylia Therapeutics. L.H.V. holds equity in Akouos and Affinia and receives sponsored research funding from Albamunity, to which he is an unpaid consultant. L.H.V. is co-founder and an employee of Ciendias Bio, a biotechnology company that pursues the development of AAV-based vaccines. L.H.V. further is a listed inventor on various gene transfer technologies, including some relevant to AAVCOVID. L.H.V. is a scientific advisory board member to Akouos, and board member of Affinia Therapeutics, companies of which he is a co-founder. U.B., N.Z. and L.H.V. are listed inventors on several patent applications on the described technologies.
(Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)