New Research Paves Way for Better Intranasal Vaccines for COVID-19 and Flu

Although gut microbiota play a critical role in the induction of adaptive immune responses to influenza virus infection, the role of nasal bacteria in the induction of virus-specific adaptive immunity is less clear. New research published this week in mBio, an open-access journal of the American Society for Microbiology, examines the role of nasal bacteria and provides clues to develop better intranasal vaccines for flu and COVID-19.

“Our study shows that both integrity and amounts of nasal bacteria can be critical for an effective intranasal vaccine,” said lead researcher Takeshi Ichinohe, Ph.D., an associate professor in the Division of Viral Infection, Division of Infectious Disease Control, International Research Center for Infectious Diseases, Institute of Medical Sciences, University of Tokyo, Minato-ku, Tokyo, Japan. “We have shown that an oral bacterial-combined intranasal vaccine protects against the influenza virus and SARS-CoV-2 infection.”

In the new study, to determine the effects of nasal bacteria in the induction of mucosal immune responses to influenza virus infection, Dr. Ichniohe and colleagues injected mice intranasally with an antibiotic cocktail to kill the nasal bacteria before influenza virus infection.

The researchers found that disruption of nasal bacteria by antibiotics before infection with the influenza virus enhanced virus-specific antibody responses. “We found that intranasal administration of antibiotics (to kill nasal bacteria) could release bacterial pathogen-associated molecular patterns (PAMP), which are bacterial components that stimulate innate immunity and act as mucosal adjuvants for the response of influenza virus-specific antibodies. said Dr. Ichniohe.

Innate immunity, which is not specific to a particular pathogen, is the first line of defense against foreign pathogens such as bacteria and viruses. The main purpose of the innate immune response is to immediately prevent the spread and movement of foreign pathogens throughout the body. The innate immune responses play an essential role in inducing the pathogen-specific adaptive immune responses. Adjuvants are substances that increase or modulate the immune response to a vaccine and stimulate the innate immune system.

The researchers also found that although the upper respiratory tract contains commensal bacteria, the relative amounts of culturable commensal bacteria in the nasal mucosa were significantly lower than those in the oral cavity. The researchers tested whether intranasal supplementation of cultured oral bacteria improves antibody responses to intranasally administered vaccine and found that oral bacteria combined with intranasal vaccine increased antibody responses to intranasally administered vaccine.

dr. Ichniohe said the findings provide clues for the development of better intranasal vaccines. “We want to develop effective intranasal vaccines for flu and COVID-19 in the near future,” said Dr. Ichniohe.

Reference: August 17, 2021, mBio.
DOI: 10.1128/mBio.01598-21