Thomas Francis Jr. Memorial Lecture

Scott E. Hensley is a Professor of Microbiology at the University of Pennsylvania and Director of the NIH-sponsored Penn Center of Excellence for Influenza Research and Response.  He received his B.A. in Biology from the University of Delaware in 2000 and his Ph.D. in Cell and Molecular Biology from the University of Pennsylvania in 2006.  He completed a postdoctoral fellowship at the National Institute of Health from 2007-2010, and was an Assistant Professor at the Wistar Institute from 2010-2016 and an Associate Professor at the University of Pennsylvania from 2016-2021. The Hensley laboratory studies mechanisms that promote antigenic drift of influenza viruses and factors that influence influenza vaccine responsiveness. The Hensley laboratory has developed new RNA-based vaccines to elicit broad immune responses against influenza viruses, and more recently has completed studies to characterize immune responses elicited by SARS-CoV-2 vaccinations and infections.

Development of a multivalent mRNA influenza vaccine to replace original antigenic sin with initial blessings of induced immunity

In a remarkable essay published in 1960, Thomas Francis, Jr. introduced the concept of ‘original antigenic sin’; the idea that antibody responses to early childhood influenza virus infections are preferentially recalled later in life upon exposure to antigenically distinct viral strains. Francis made clear that he thought the real ‘sin’ was that humans are infected with only one influenza virus strain in early childhood, leading to narrower immunological memory than multiple influenza virus strains would deliver. Francis envisioned vaccines that would deliver ‘initial blessings of induced immunity’ to infant immune systems that could be recalled later in life. Here, we attempted to fulfill his vision by creating a multivalent nucleoside-modified mRNA vaccine encoding hemagglutinins from every known influenza virus subtype. We show that this vaccine elicits antibodies in mice, ferrets, and non-human primates that react to all encoded antigens. The vaccine elicits strong responses in animals with and without prior influenza virus exposures and protects against matched and mismatched viral strains. We propose that multivalent mRNA influenza vaccines have the potential to induce ‘initial blessing of induced immunity’ in previously naïve individuals, while providing an absolution of ‘original antigen sin’ in the rest of us.

Dr. Arnold S. Monto is the Thomas Francis Collegiate Professor of Public Health at the University of Michigan School of Public Health. A professor of epidemiology and of global public health, his work has focused on the occurrence, prevention, and treatment of acute infections in the individual and the community.

Throughout his career spanning seven decades, Dr. Monto, has been involved in pandemic planning and emergency response to influenza and other respiratory virus outbreaks, including the 1968 Hong Kong influenza pandemic, avian influenza, SARS, MERS and the COVID-19 pandemic and is the author of over 350 research papers focusing on the epidemiology and implications of respiratory infections and co-editor of Textbook of Influenza – Second Edition.

Born in Brooklyn, New York, Dr. Monto received a B.S. in zoology from Cornell University in 1954 and earned his M.D. from Cornell University Medical College in 1958. He completed his internship and residency in medicine at the Vanderbilt University Medical Center and was a Postdoctoral Fellow in Infectious Diseases at Stanford University Medical Center in 1960-1962. Dr. Monto fulfilled his national service commitment in the Virus Diseases Section of the Middle America Research Unit, part of the National Institute of Allergy and Infectious Diseases. While there, he began his career-long interest in respiratory illnesses confirming that the same viruses causing illnesses in the temperate zones cause illnesses in the tropics. He was among the first to observe that influenza mainly occurred in the rainy season in areas where temperatures were stable year-round.

In 1965, Dr. Monto was recruited to the University of Michigan School of Public Health by Thomas Francis Jr., professor, and chair of the school’s Department of Epidemiology. He collaborated with Francis who led the landmark Tecumseh Community Health Survey which looked at behavioral, environmental, and family factors associated with cardiovascular disease and other chronic conditions.

Dr. Monto expanded the study’s scope, and the Tecumseh Study of Respiratory Illness studied the spread of respiratory infections in 10,000 residents of Tecumseh, Mich. Dr. Monto described the specific viruses involved in causing illnesses in American families over an 11-year period. During the 1968 influenza pandemic, Dr. Monto found that vaccinating school-age children reduced infection in the entire community, an early demonstration of herd immunity.

Since then, Dr. Monto has been involved in evaluating a variety of strategies to control influenza including vaccines, antivirals, and non-pharmaceutical interventions such as antiseptic tissues and face masks. He designed and carried out critical studies evaluating the value of the neuraminidase inhibitors now in use for influenza. In the 2000s he was involved in developing pandemic control strategies including social distancing, leading to work at WHO and in the US during the 2009 swine flu pandemic. He also led clinical trials establishing the superiority of inactivated vaccines compared to live attenuated vaccines in preventing influenza in adults.

At Michigan, Dr. Monto has led several departments, centers and initiatives including as chair of the school’s Department of Population Planning and International Health (1993-1996), director of the U-M Center for Population Planning (2002-2004), director of the University of Michigan Bioterrorism Preparedness Initiative. He is the co-director of the Michigan Flu Lab, one of five centers across the country that collects data for the Centers for Disease Control and Prevention. In 2010, he was named the Thomas Francis Collegiate Professor of Public Health.

Also in 2010, Dr. Monto established the Household Influenza Vaccine Evaluation (HIVE) Study, designed to allow the study of many aspects of infection occurrence and prevention over time. The study has resulted in several notable findings related to natural infection with different viruses and the immune correlates of protection from different influenza vaccines. It was the first to demonstrate the potential problems with the serial use of such vaccines.

Dr. Monto was the plenary speaker for a 2017 NIH-led workshop of U.S. and international experts from academia, industry, and government to develop a strategic plan and research agenda aimed at the development of a universal influenza vaccine which also allows the study over time of other respiratory viruses including the coronaviruses. He’s involved in other studies assessing influenza vaccine effectiveness in preventing medical encounters and hospitalization with a goal of improving protection. A study in progress addresses the role of antivirals in seasonal and pandemic influenza control.

Dr. Monto has been a member of the Pandemic Influenza Task Force of the Infectious Disease Society of America since 2007, and has been a member of the European Scientific Working Group on Influenza (2009–2016), the World Health Organization’s Influenza Pandemic Emergency Committee (2009–2010) and the President Barack Obama’s Council of Advisors on Science and Technology H1N1 Working Group (2009). He’s been an advisor to the US State Department, the Health Committees of House of Commons and Senate, Ottawa, and the U.S. Department of Defense. In 2009 he was awarded the Alexander Fleming Award for Lifetime Achievement by the Infectious Diseases Society of America.

From avian flu to Covid-19:How the US pandemic response has evolved

Dr. Kathleen Neuzil is the Myron M. Levine Professor in Vaccinology, Professor of Medicine and Pediatrics, and the Director of the Center for Vaccine Development and Global Health at the University of Maryland School of Medicine. She is an internationally recognized research scientist and advocate in the field of vaccinology. Throughout her career, Dr. Neuzil has conducted clinical and epidemiologic studies on vaccine-preventable diseases, yielding high-profile publications that inform policy decisions and public health actions. Dr. Neuzil’s work has spanned dozens of low-resource countries with multiple vaccines, including influenza, rotavirus, human papillomavirus, Japanese encephalitis, typhoid conjugate vaccines, and most recently, COVID-19 vaccines. Dr. Neuzil is central to the domestic and global response to COVID. As a co-PI of the NIH-funded Leadership Group for the Vaccine and Treatment Evaluation Unit network, Dr. Neuzil is part of the strategic team evaluating COVID vaccines and therapeutics in the US. Dr. Neuzil also directs TyVAC, the Typhoid Vaccine Acceleration Consortium, with the goal to accelerate the introduction of typhoid conjugate vaccines into low-resource countries. She has more than 280 scientific publications on vaccines and infectious diseases. Dr. Neuzil's research capabilities are complimented by 20 years of involvement in domestic and international policy, including past membership on the US Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices. She is a member of the World Health Organization Strategic Advisory Group of Experts on Immunization and is a member of the prestigious National Academy of Medicine. 

Typhoid Conjugate Vaccines: Achieving their potential for disease prevention and health equity

Typhoid fever disproportionately impacts children and poor populations, a trend that is likely to grow with increasing urbanization and climate change. Combined with the growing problem of multi-drug resistance, the prevention and control of Salmonella enterica serovar Typhi (S. Typhi) is a global health priority. At present, vaccines for typhoid fever are underutilized despite the substantial disease burden and a World Health Organization (WHO) recommendation for the use of typhoid vaccines. Typhoid Conjugate Vaccines (TCV)s, which may be given to children as young as 6 months of age and are expected to have longer duration of immunity than polysaccharide vaccines, should overcome many of the challenges that have impeded uptake of the earlier vaccines. Dr. Neuzil will discuss new trial data and early experiences with low resource country introduction and programmatic use of TCVs.

Jonathan Van-Tam Kt, MBE, FMedSci, is a public health specialist with a clinical background in emergency medicine, anaesthesia and infectious diseases. He is an expert on respiratory viruses and pandemics and currently Pro Vice-Chancellor, Faculty of Medicine and Health Sciences, University of Nottingham. His career has also taken him to Public Health England, the World Health Organization, and the pharmaceutical and vaccine industries. Jonathan was seconded to the Department of Health and Social Care in 2017-22 as Deputy Chief Medical Officer. He is well-known for his leadership role during the COVID-19 pandemic, particularly his straight, no-nonsense, communication style from the podium at No.10 Downing Street, and for the acquisition and rollout of vaccines and antiviral drugs in the UK. He received a knighthood from Her Majesty the Queen in her 2022 New Year’s Honours List, for services to public health. He has recently been awarded the Royal Society’s Attenborough Award and Lecture 2022, for outstanding public engagement in science.