Multiparametric Flow Cytometry Analysis of Cell-mediated Immunity in Clinical Trials: A Case-study Using Plant-derived Virus-like Particles (VLP) in Influenza Vaccines

Influenza infections are endemic in several regions of the world. The World Health Organization estimates that between 250,000 – 500,000 people die annually due to seasonal influenza viral infection, including 36 000 deaths in the USA alone. In the past century, the world has witnessed at least 4 influenza pandemics responsible for millions of deaths on a global scale. Estimates from the most recent pandemic (H1N1, 2009-2010) place the world-wide toll between 123,000 and 203,000 deaths, highlighting the need for faster and scalable approaches to developing and deploying new, more effective influenza vaccines.

In this scientific webinar, Caprion and Medicago will describe how the production of Virus-Like Particle (VLP)-based vaccines using plant-based transient expression technology has particular advantages for accelerating both the development of new vaccines and the scaling-up of production for deployment in affected areas. Vaccine lots, which exactly match the specific strain(s) in circulation can be generated within a month of strain identification. This is a significant improvement compared to more traditional fertilized chicken egg-based platforms, which require half a year or more for viral strain production. Plant-based VLP technology is rapid, scalable and relatively low-cost, with the added safety advantage that the VLP contains no genetic material, rendering it non-infectious and unable to replicate.

Hemagglutination inhibition (HI) antibody titers, the only universally accepted immune correlate of protection against influenza, does not necessarily translate into protection, and clinical benefit may be short-lived, particularly in the elderly. Recent studies in animal models have suggested that in situations where antibodies fail to confer protection, cell-mediated immunity may be able to act alone, suggesting that some shortcomings currently associated with influenza vaccines might be surmounted via use of novel vaccines which elicit CD4 and CD8 T cell responses. Therefore, in the current clinical immune monitoring study, the specificity and magnitude of CD4 and CD8 T cell response were measured following immunization. The data presented will show how multiparametric flow cytometry and related analytical tools allow monitoring the diversity and distribution of Influenza-specific cellular subsets both at the phenotypic and functional level in the context of a clinical trial.

The results of these major studies were published in the recent issue of Clinical Immunology, entitled “Influenza virus-like particle vaccines made in Nicotiana enthamiana elicit durable, poly-functional and cross-reactive T cell responses to influenza HA antigens”.

Speakers

Jean-Francois Poulin, PhD, MBA, Senior Principal Scientist and Business Development Liaison, Caprion/IMMUNECARTA Services

Jean-Francois joined ImmuneCarta in 2008 and is currently responsible for the management of several clinical immune monitoring studies in the field of oncology and viral infection. He obtained his undergraduate degree in biochemistry from the University of Montreal before completing a Ph.D. in immunology at McGill University where he developed a novel method to monitor human thymic activity. His postdoctoral studies were performed in the laboratory of Joseph McCune’s at UCSF where he studied HIV virology. Before joining ImmuneCarta, Dr. Poulin worked at Emerillon Therapeutiques, a Montreal start-up. Jean-Francois also holds an executive MBA from the University of Quebec at Montreal.

Message Presenter

Stéphane Pillet, PhD, Scientifique immunologie / Scientist Immunology, Medicago Inc.

Stephane Pillet is a Scientist Immunology at Medicago and a Research Associate at the Research Institute of the McGill University Health Centre. Prior to joining Medicago, Dr. Pillet worked for the Public Health Agency of Canada at the National Microbiology Laboratory on the characterization of the cell-mediated immunity (CMI) as an immune correlate of protection in vaccine strategies and immune therapies against highly pathogenic influenza and Ebola viruses in mice, ferret and non-human primates.

Dr. Pillet holds a Ph.D. in immunotoxicology from the University of Liège (Belgium) where he studied the impact of gender and age on immunomodulatory drugs and chemicals. During his post-doctoral fellowship, he focused on virus-host interactions in ferrets infected with highly virulent pathogens and developed new immunological tools to assess cell mediated immunity in that animal model. Stephane Pillet is currently managing pre-clinical studies aiming to better characterize the immunogenicity, and particularly the CMI, elicited by plant origin virus-like particle vaccine candidates. He leads the development of CMI assessment strategies and data analysis of Medicago vaccine candidate clinical trials in close collaboration with ImmuneCarta.

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