Andrew Pekosz Addresses Influenza Mutations at 2024 LaMontagne Symposium

Dr. Andrew Pekosz, PhD was the keynote speaker at the 2024 John Ring LaMontagne Annual Keynote Lecture and Symposium which was held March 26, 2024 on the UT Campus. The title of his lecture was Virus Surveillance and the Identification of Novel Genetic Mutations that Facilitate Virus Circulation.

Dr. Pekosz is Professor and Vice Chair at the W. Harry Feinstone Department of Molecular Microbiology and Immunology in the Bloomberg School of Public Health at Johns Hopkins University. He is also Co-director of the Johns Hopkins Center of Excellence for Influenza Research and Response (CEIRR) and Director of the Center for Emerging Viruses and Infectious Diseases at Johns Hopkins.

At the beginning of the lecture, Pekosz explained how he and his team at CEIRR study the Influenza A virus (the type of flu that typically causes both seasonal flu epidemics and pandemics). They connect labs across the country, surveying infected populations and sequencing the virus from infected individuals to identify specific viruses at an early stage. They can then move forward to select the viruses to study in vitro in cultures, as well as from blood and peripheral blood mononuclear cells (PBMCs) to study immune response. When the team at CEIRR studies the virus, they use human nasal epithelial cell cultures from disease-free human cells that are similar to the human respiratory tract. This enables them to more accurately reflect how the virus infects human cells. Then they establish a more holistic view of how influenza impacts the population on an annual basis. They use this to improve responses so they can get better and faster at identifying infections and getting people appropriate treatments. 

Pekosz also discussed the mechanisms of how the influenza virus mutates to create new versions. Influenza A is an RNA virus that has a segmented genome. Hemagglutinin (HA) and Neuraminidase (NA) are two of the proteins in the virus that are key to infection. HA attaches the virus to cells in the human body. Vaccines mainly target this protein, causing the body to produce neutralizing antibodies to this protein. Antibodies to NA are produced from infection, rather than from vaccines. Subtypes and clades, which are major and minor genetic mutations of these proteins in the virus, create differences in the proteins that affect infection and how the viruses behave. 

In addition to mutations, Pekosz explained, the virus can go through gene reassortment which occurs when two slightly different flu viruses infect the same cell. Then they can exchange gene segments and so create viruses that are combinations between the two. These have different properties, increasing diversity and responding to pressures such as antibodies or the use of antiviral drugs, to make it easier for the virus to infect human cells. Therefore, both mutations and gene reassortments can make it trickier to create vaccines that effectively target the flu virus each year.

Looking at previous flu seasons, Pekosz demonstrated how the influenza viruses dominant during those seasons mutated and thus affected the efficacy of vaccines. He first examined how major changes in the dominant H3N2 flu strain developed between the 2016-17 and 2017-18 flu seasons. Mutations and gene reassortments combined to make H3N2 replicate better and evade vaccines, increasing the number of cases in 2017-18 and making it the worst flu season since the flu pandemic of 2009. 

H1N1 became the dominant flu strain during the 2019-2023 seasons, coinciding with the COVID-19 pandemic. Pekosz discussed the development of new versions of the strain from 2019-2023. In 2019-20, before COVID gained a stronghold, H1N1 was very strong. From 2020-21, the strain was almost non-existent. However, H1N1 “emerged with a vengeance” in the 2021-22 flu season and became the dominant flu strain. Pekosz then demonstrated the various mutations that lead to H1N1 becoming more virulent and better able to escape vaccine-induced immunity in the 2022-23 season.

Addressing the efficacy of flu vaccines, Pekosz said, “It isn’t about ‘bad’ vaccines; the virus is constantly undergoing a dance with the human immune system and the human epithelial cells that it has to replicate in and it’s finding various combinations … to escape from immune responses.” Therefore, he said, this makes the virus a moving target for vaccines, “which contributes to the difficulties in terms of using our current vaccines as a more effective way of reducing influenza burden in the population. We need to better understand these mutations so that we can better target prevention and treatment.”

 

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