Vaccination against pathogenic influenza with synthetic consensus DNA antigens / Dominick J. Laddy.

Format:

Book

Manuscript

Microformat

Thesis/Dissertation

Author/Creator:

Laddy, Dominick J.

Contributor:

Weiner, David B., advisor.

University of Pennsylvania.

Language:

English

Subjects (All):

Penn dissertations--Pharmacological sciences.

Pharmacological sciences--Penn dissertations.

Pharmacological Sciences.

Academic Dissertations as Topic.

Medical Subjects:

Pharmacological Sciences.

Academic Dissertations as Topic.

Local Subjects:

Penn dissertations--Pharmacological sciences.

Pharmacological sciences--Penn dissertations.

Physical Description:

vii, 123 pages : illustrations ; 29 cm

Production:

2008.

Summary:

The persistent evolution of highly pathogenic avian influenza (HPAI) highlights the need for novel vaccination techniques that can be quickly and effectively employed to respond to emerging viral threats. We evaluated the use of optimized consensus influenza antigens to provide broad protection against divergent strains of H5N1 influenza in three animal models of mice, ferrets, and non-human primates. We also evaluated the use of in vivo electroporation to deliver these vaccines to overcome the immunogenicity barrier encountered in vaccinating against H5N1 influenza in addition to larger animal models of DNA vaccination. By combining several consensus influenza antigens with in vivo electroporation, we demonstrate that these antigens induce both protective cellular and humoral immune responses in mice, ferrets and non-human primates. In addition, the antibodies induced by the synthetic consensus H5 hemagglutinin were able to inhibit both clade-matched and highly divergent H5N1 influenza viruses. We also demonstrate the ability of these antigens to protect from both morbidity and mortality in a ferret model of HPAI, in addition to the inhibition of viral replication in a non-human primate model, in both the presence and absence of neutralizing antibody, which will be critical in responding to the antigenic drift that will likely occur before these viruses cross the species barrier to humans.

Notes:

Adviser: David B. Weiner.

Thesis (Ph.D. in Pharmacological Sciences) -- University of Pennsylvania, 2008.

Includes bibliographical references.

Local Notes:

University Microfilms order no.: 3346148