Replication-Defective Adenovirus Serotype 5 Vectors Elicit Durable Cellular and Humoral Immune Responses in Nonhuman Primates

Author:

Santra Sampa1,Seaman Michael S.1,Xu Ling2,Barouch Dan H.1,Lord Carol I.1,Lifton Michelle A.1,Gorgone Darci A.1,Beaudry Kristin R.1,Svehla Krisha2,Welcher Brent2,Chakrabarti Bimal K.2,Huang Yue2,Yang Zhi-Yong2,Mascola John R.2,Nabel Gary J.2,Letvin Norman L.12

Affiliation:

1. Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115

2. Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-3005

Abstract

ABSTRACT The magnitude and durability of immune responses induced by replication-defective adenovirus serotype 5 (ADV5) vector-based vaccines were evaluated in the simian-human immunodeficiency virus/rhesus monkey model. A single inoculation of recombinant ADV5 vector constructs induced cellular and humoral immunity, but the rapid generation of neutralizing anti-Ad5 antibodies limited the immunity induced by repeated vector administration. The magnitude and durability of the immune responses elicited by these vaccines were greater when they were delivered as boosting immunogens in plasmid DNA-primed monkeys than when they were used as single-modality immunogens. Therefore, administration of ADV5-based vectors in DNA-primed subjects may be a preferred use of this vaccine modality for generating long-term immune protection.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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