Every summer, Aubree Gordon, an epidemiologist at the University of Michigan in Ann Arbor, spends about a month in Managua, Nicaragua, when the rainy season is in full swing. But Gordon is interested in a different kind of season. “June or July can be peak influenza time in Nicaragua,” Gordon says.
Since 2011, she and her colleagues at the Managua site of the Sustainable Sciences Institute, headquartered in Oakland, California, have been tracking flu infections, vaccinations and immune responses in hundreds of children enrolled in the Nicaraguan Pediatric Influenza Cohort study. The work is part of the larger Dissection of Influenza Vaccination and Infection for Childhood Immunity (DIVINCI) study, which is following some 3,000 children in the United States, Nicaragua and New Zealand, most of them from birth. Through the study of antibodies, immune cells and viral genomes, the researchers hope to understand a mysterious feature of the human immune response to the rapidly evolving flu virus.
Nature Spotlight: Influenza
Influenza frequently alters the proteins on its surface, so that over a lifetime, a person encounters many slightly different varieties of the virus. But the immune system generally sticks to what worked before. “Our earliest childhood exposures with influenza viruses prime antibody responses that last a lifetime,” says Scott Hensley, a microbiologist at the University of Pennsylvania in Philadelphia.
This phenomenon is known as original antigenic sin (OAS) — antigenic derives from antigen, which refers to any part of a virus to which an antibody binds. The term OAS comes from researchers who, in the 1950s, recognized that most of the flu-binding antibodies circulating in people’s blood match whichever influenza strains were most prevalent during their childhood1.
The emergence of swine and avian influenzas has made it possible to observe OAS in action, owing to it providing protection to people who had been imprinted by similar flu varieties decades earlier. However, it is hard to predict when this bias for ‘retro’ antibodies will help or hamper immune responses to current strains and updated vaccines. Some evidence suggests that the body’s tendency to boost old immune responses to fight off infection might limit its ability to detect parts of the flu virus that have recently changed.
Now, researchers are trying to define the biological basis of OAS and design vaccines that could take advantage of it — or override it to generate immunity against a wider variety of flu strains. Longitudinal studies such as DIVINCI are poised to provide the data to make this possible. “The challenge for vaccinology is understanding how to work better with the memory that’s available,” says Sarah Cobey, an evolutionary virologist at the University of Chicago in Illinois. Yet shifting policies at the US National Institutes of Health (NIH) under the administration of President Donald Trump have created uncertainty about future funding of these studies.
Not so sinful
The benefit of OAS was clearly demonstrated in a 2016 study2 that is often credited with reigniting widespread interest in the phenomenon. In that study, researchers used statistical modelling to correlate people’s birth years with the flu subtype they were most likely to have first been exposed to.
A health-worker takes a swab as part of a long-running flu study in Nicaragua.Credit: Marc-Gregor Camprendon
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