Background
Influenza viruses (as well as coronaviruses) continuously circulate in the human population. During their circulation and replication, they keep accumulating mutations that may change antigenic structures. This is called antigenic drift and is the reason why we currently need to update influenza vaccines each year, to keep up with the changing virus.
Influenza vaccines generate an immune response against the influenza virus, but, more importantly, boosts your immunological memory against it. Immunological memory consists of both immune cells (memory T cells and memory B cells) and their molecular products such as antibodies. Upon a second vaccination or viral exposure, T and B cell are re-activated to rapidly recognize and neutralize the influenza virus, thereby preventing the disease. This is the core concept of immunity.
However, it has been shown that the immune system and memory can become hyper-focused on the first version (strain) of influenza virus it experienced. This can result in skewed immune responses that are unable to respond properly to new influenza strains. This concept has been called “Original Antigenic Sin” or is sometimes simply referred to as “immune imprinting” (see below Figure). The extent of imprinting during childhood is important as it may set the boundaries for later immune formation, and potentially influence the risk of severe disease later in life.
Original Antigenic Sin as a concept was first described in 1960, and our understanding of the mechanism has since gradually evolved. However, it has not been possible until very recently to investigate immunity at a single cell level, which also means that there still remain a knowledge gaps on how and why immunological imprinting is happening.
Master’s Project
The aim of this project will be to study the mechanisms of immune imprinting by influenza viruses. This will involve detailed studies of immune responses to influenza after multiple infections, including where on the virus the response is directed, and if this changes with different strains and number of infections. This can then be applied to examine the impact this has on influenza vaccine effectiveness.
The student will be trained in all relevant methods, and learn state-of-the-art animal models and analytical methods. Our research group is located to Rikshospitalet, and the student will here benefit from participation in seminars and meetings within the Gr?deland research group, as well as with other external and internal partners. The knowledge generated within this project is expected to be valuable for a rapidly evolving field of immunology with importance for future vaccine design.
Relevant methods
Vaccination of mice and blood sample collection, adoptive B cell transfer, ELISA, neutralization assay, high-parameter flow cytometry.
References and Further Reading
- Zhang A, Stacey HD, Mullarkey CE, Miller MS. Original Antigenic Sin: How First Exposure Shapes Lifelong Anti–Influenza Virus Immune Responses. The Journal of Immunology (2019) 202:335–340. doi: 10.4049/jimmunol.1801149
- Knight M, Changrob S, Li L, Wilson PC. Imprinting, immunodominance, and other impediments to generating broad influenza immunity. Immunol Rev (2020) 296:191–204. doi: 10.1111/imr.12900
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Gostic KM, Bridge R, Brady S, Viboud C, Worobey M, Lloyd-Smith JO. Childhood immune imprinting to influenza A shapes birth year-specific risk during seasonal H1N1 and H3N2 epidemics. PLoS Pathog (2019) 15:e1008109. doi: 10.1371/journal.ppat.1008109
