Name: Kanta Subbarao
Affiliation: Director, WHO Collaborating Centre for Reference and Research on Influenza
Professor, Department of Microbiology and Immunology
Peter Doherty Institute for Infection and Immunity
University of Melbourne
Could you tell me a bit about what your research entails?
I am particularly interested in influenza viruses at the animal-human interface that pose a pandemic threat. My research program focuses on two distinct areas: the biology of influenza viruses and vaccine development. On the virus biology side, I am primarily interested in viral determinants of disease pathogenesis including virulence, host-range and airborne transmissibility. With regard to vaccine development, I have spent a number of years designing and evaluating pandemic influenza virus vaccines using the live attenuated vaccine platform. We have shown that live attenuated pandemic influenza vaccines induce long lasting immune memory and I am now interested in combining vaccine platforms to induce broadly cross protective immunity.
In November 2016, after 14 years in the Laboratory of Infectious Diseases in the intramural research program of NIAID, NIH, I moved to Australia. In my new position, my focus is on basic and translational research to (1) understand the immune response to influenza infection and vaccination in order to improve influenza vaccines; (2) understand the biology of avian influenza viruses that pose a pandemic threat and (3) evaluate measures to reduce the impact of influenza in vulnerable populations including the elderly.
How did you become interested in influenza research?
I trained as a physician and subsequently specialized in paediatrics and paediatric infectious diseases. During my Peds ID fellowship, my laboratory research was on Respiratory Syncytial Virus (RSV), which is the most important respiratory pathogen in children. I loved my experience in virology and, in seeking further research training, I was referred to Drs. Brian Murphy and Robert Chanock in the Laboratory of Infectious Diseases (LID) at the NIH in Bethesda. The LID had an active research program on respiratory viruses, including RSV, but the RSV positions were committed and Brian convinced me to join the influenza program. I was enormously intimidated by the long history of influenza research and went around muttering H1N1, H2N2, H3N2 memorizing the names of the prototype viruses that rolled off people’s tongues so effortlessly! After the first 6 months, there was no looking back -I loved the fact that influenza viruses weren’t as fragile as RSV, the genetic manipulations that were possible by reassortment (in the era before reverse genetics) and was encouraged by the unique opportunities for bench to bedside research at LID. I no longer have lingering regrets about giving up involvement with clinical medicine and have immersed myself fully in influenza virus research.
In what ways has the 1918 pandemic most influenced your research, and the wider virology and public health field?
The fear and awe surrounding the devastating morbidity and mortality of the 1918 pandemic has always cast a large shadow over the fields of infectious disease, virology and public health in which I trained. The accomplishments (see Q4 below) that led to the reconstruction of the 1918 virus extended beyond into the wider research arena and influenced research on other influenza viruses. Since 1997, I have worked on influenza viruses that pose a pandemic threat, where the spectre of a pandemic on the scale of the 1918 pandemic is often evoked. It is certainly the worst-case scenario and the benchmark against which pandemics are compared. A guiding principle in public health is to prepare for the worst but the next 3 pandemics (1957, 1968 and 2009) have not been as severe as the 1918 pandemic. I fear that if we don’t balance these lessons with the 1918 experience and temper our message and manage expectations, we will lose credibility with policy makers and the public.
What do you see as the biggest accomplishments/breakthroughs in the field since the 1918 pandemic? Are there any papers that you feel are must reads for those that aren't familiar with the field (and briefly, why)?
- The isolation of influenza virus (Smith, Andrewes and Laidlaw. Lancet 225: 66-68; 1933)
- Genetic reassortment of influenza viruses (Hirst and Gotlieb. J Exp Med 98: 41-52, 1953 and Kilbourne. Bull WHO 41: 643-645, 1969). This technique made the development of inactivated and live attenuated vaccines with a core set of internal genes that conferred desirable properties such as high-yield in eggs or attenuation on circulating wild type viruses possible.
- The development of plasmid based reverse genetics (Fodor et al J Virology 73: 9679-82, 1999 and Neumann et al PNAS 96: 9345-50, 1999) revolutionized our ability to study the contribution of individual residues in a gene segment to phenotypes of the virus.
- Recovering the sequence of the 1918 H1N1 virus from paraffin embedded tissue sections (Taubenberger et al Science 275: 1793-96, 1997). This laborious and meticulous work made it possible to study the virus that was responsible for the 1918 pandemic.
What do you see as the main challenges for research in your part of the field in the coming years?
- Putting together the richly detailed information gleaned from reductionist research on the virus and host cells into what happens in the intact host. For example, what makes some influenza viruses transmit easily from person to person while others don’t, or what makes some influenza viruses more virulent than others? There aren’t as many physicians electing to pursue a research career in virology now as there were 20 years ago. MDs and PhDs often approach research questions from slightly different angles - diversity enriches the field. Such multidisciplinary teams may achieve breakthroughs in the study of influenza in the intact host.
- We must improve influenza vaccines- a universal vaccine would be an amazing achievement, but I would take a broadly cross reactive vaccine gladly. The NIH has recognized this as a major challenge.
- The enhanced scrutiny on research on respiratory viruses with pandemic potential, multiple layers of often-overlapping regulation and funding pauses have adversely affected the enthusiasm and morale of young scientists interested in influenza research. Hopefully, we will recover from this and will attract bright and talented scientists into the field.