Maxfield, LoriAbbink, PeterStephenson, KathrynBorducchi, Erica N.Ng'ang'a, DavidKirilova, Marinela M.Paulino, NoelixBoyd, MichaelShabram, PaulRuan, QianPatel, MayankBarouch, Dan2015-12-042015Maxfield, L. F., P. Abbink, K. E. Stephenson, E. N. Borducchi, D. Ng'ang'a, M. M. Kirilova, N. Paulino, et al. 2015. “Attenuation of Replication-Competent Adenovirus Serotype 26 Vaccines by Vectorization.” Clinical and Vaccine Immunology : CVI 22 (11): 1166-1175. doi:10.1128/CVI.00510-15. http://dx.doi.org/10.1128/CVI.00510-15.1556-6811http://nrs.harvard.edu/urn-3:HUL.InstRepos:23845168Replication-competent adenovirus (rcAd)-based vaccine vectors may theoretically provide immunological advantages over replication-incompetent Ad vectors, but they also raise additional potential clinical and regulatory issues. We produced replication-competent Ad serotype 26 (rcAd26) vectors by adding the E1 region back into a replication-incompetent Ad26 vector backbone with the E3 or E3/E4 regions deleted. We assessed the effect of vectorization on the replicative capacity of the rcAd26 vaccines. Attenuation occurred in a stepwise fashion, with E3 deletion, E4 deletion, and human immunodeficiency virus type 1 (HIV-1) envelope (Env) gene insertion all contributing to reduced replicative capacity compared to that with the wild-type Ad26 vector. The rcAd26 vector with E3 and E4 deleted and containing the Env transgene exhibited 2.7- to 4.4-log-lower replicative capacity than that of the wild-type Ad26 in vitro. This rcAd26 vector is currently being evaluated in a phase 1 clinical trial. Attenuation as a result of vectorization and transgene insertion has implications for the clinical development of replication-competent vaccine vectors.en-USJournal Article2015-12-0410.1128/CVI.00510-15