CPB 697 RESEARCH SEMINAR

DEPARTMENT OF COMPARATIVE PATHOBIOLOGY

Neetu Singh, BVSC & AH, MVSc

Graduate Student in Molecular Virology

Department of Comparative Pathobiology

Purdue University

“Development Of Adenoviral-Vector–Based Pandemic Influenza Vaccine”

Thursday, November 16, 2006

VPTH 112

3:30 p.m.

ASTRACT:

Avian H5N1 virus is an influenza A virus subtype. The highly pathogenic avian H5N1 virus currently circulating in Asia, Europe, the Middle East and Africa could potentially cause the next pandemic, once it gains the ability of human–to-human transmission. One of the important strategies to combat the threat of pandemic is to develop an effective vaccine. The currently licensed human vaccines are subtype-specific and do not protect against these H5N1 viruses. Our goal is to develop an egg-independent vaccine strategy that will assure the uninterrupted production of the vaccine in case of an influenza pandemic, when there could be scarcity of embryonated eggs, as the H5N1 virus is highly lethal to chickens.

We generated a replication-incompetent, human adenoviral vector (HAd-H5HA) expressing subtype 5 hemagglutinin. Immunization of mice with HAd-H5HA induced both humoral and cell-mediated immune responses significantly better than that of a traditional subunit vaccine when tested against H5N1 viruses isolated from people. Vaccinated mice were effectively protected from H5N1 disease, death, and primary viral replication when challenged with antigenically distinct H5N1 strains. In addition, this vaccine induced significant number of HA-specific CD8 T cells as assessed by MHC-pentamers and IFN-gamma secreting cells by ELISpots.

The study highlights the potential of an adenoviral vector-based delivery system, which is both egg-independent and adjuvant-independent and offers stockpiling options for the development of a pandemic influenza vaccine. The ongoing study involving nonhuman adenoviral vectors as the delivery system, aimed at providing broader protection against pandemic influenza will also be discussed.