Findings suggest future vaccines use natural antibodies to target both infection and spread

Today’s influenza vaccines primarily prevent infection in individuals, but new research led by the University of Michigan and the Institut Pasteur suggests that incorporating antibodies generated after infection could lead to more powerful vaccines by also reducing person-to-person transmission.

Future vaccines that boost the antibodies—neuraminidase, or NA, in particular, along with, HA head and HA stalk (HA stands for hemagglutinin)—may add an important layer of community protection, the researchers say.

“NA is a part of the influenza virus that has been relatively overlooked in vaccine design yet they play a key role not only in lowering infection risk but also in reducing how contagious someone becomes when infected,” said Aubree Gordon, co-senior study author and director of the Michigan Center for Infectious Disease Threats and Pandemic Preparedness.

The study is published in the journal Nature Communications and was funded by the National Institutes of Health in the U.S. It comes amid warnings of a severe flu season ahead and as the first deaths of the 2025-2026 flu season are being recorded in the Northern Hemisphere. Influenza infects upwards of one billion people and leads to some 650,000 deaths globally each year. Lost productivity and hospitalizations due to the flu also result in major economic loss and burden.

“Modifying vaccines to include NA antibodies provides an extra layer of defense that’s especially important for infants, immunocompromised individuals and others who can’t mount strong vaccine responses,” said Gordon, an epidemiologist from the School of Public Health. “This could also be very important if we were to have an influenza pandemic.”

She helped lead a multinational research team that followed 171 Nicaraguan households and their 664 contacts over three influenza seasons—2014, 2016, 2017. Almost all of the participants had never been vaccinated, allowing researchers to observe transmission patterns driven primarily by antibodies from infection.

Through bloodwork, virologic testing and the power of mathematical modeling, the researchers identified which antibodies were most effective at limiting spread.

Senior co-author Simon Cauchemez, epidemiologist and infectious disease modeller from Institut Pasteur and its Mathematical Modelling of Infectious Diseases Unit, said the detailed household data and modeling methods let the researchers chart and document how the antibodies reacted and which were most powerful in keeping an infected person from spreading the flu to people they came into contact with.

“Understanding which factors drive the spread of influenza is essential to design more effective control strategies but often challenging. Here, we were able to obtain such insight thanks to the analysis of very detailed data documenting influenza transmission in households with state-of-the-art modelling techniques,” Cauchemez said.

Very few people in the study were vaccinated, giving the researchers watch how immunity, primarily from prior infection, impacts the chances you’ll get influenza and whether you spread it to others. It’s an important distinction because people who get influenza can be strongly protected against that same type of influenza for many years while vaccines to influenza tend to provide moderate protection for less than a year.

“By studying immunity after infection,” the authors wrote, “we can identify which antibody responses are most protective and translate those insights into improved vaccine designs that provide stronger and longer-lasting protection.”

Study co-authors: Gregory Hoy, University of Michigan Medical School and School of Public Health; Thomas Cortier, Institut Pasteur and Sorbonne Universite; Hannah Maier and Abigail Shotwell, U-M School of Public Health; Guillermina Kuan, Sustainable Sciences Institute and Centro de Salud Sócrates Flores Vivas, Ministry of Health, both in Managua, Nicaragua; Roger Lopez and Angel Balmaseda, Sustainable Sciences Institute, Managua, Nicaragua and Laboratorio Nacional de Virología, Centro, Nacional de Diagnóstico y Referencia, Ministry of Health, Managua, Nicaragua; Nery Sanchez, Sergio Ojeda and Miguel Plazaola, Sustainable Sciences Institute, Managua, Nicaragua; Daniel Stadlbauer, Icahn School of Medicine; Florian Krammer, Icahn School of Medicine, Center for Vaccine Research and Pandemic Preparedness, and Ignaz Semmelweis Institute.