The role of nasal bacteria in virus-specific adaptive immunity is a major question with a material impact on development of intranasal vaccines for respiratory diseases such as COVID-19 and flu. A new study from researchers at the University of Tokyo made some key findings about this process.
The researchers found that giving mice intranasal antibiotics before influenza virus infection enhanced virus-specific antibody response in a MyD88-dependent manner. Likewise, lysozyme enhanced antibody responses to intranasally administered influenza virus hemagglutinin (HA) vaccine also enhanced antibody response in the same manner. Further, intranasal supplementation of cultured oral bacteria from a healthy human volunteer improved antibody response to an intranasally administered vaccine.
They report that “Our results reveal the role of nasal bacteria in the induction of the virus-specific adaptive immunity and provide clues for developing better intranasal vaccines.” The research was published this week in mBio, an open-access journal of the American Society for Microbiology.
“Our study shows that both integrity and amounts of nasal bacteria may be critical for effective intranasal vaccine,” said study principal investigator Takeshi Ichinohe, PhD, an associate professor in the Division of Viral Infection, Department of Infectious Disease Control, International Research Center for Infectious Diseases, Institute of Medical Science, the University of Tokyo. “We showed that oral bacteria-combined intranasal vaccine protects from influenza virus and SARS-CoV-2 infection.”
There are many perceived advantages of an intra-nasal vaccine for a respiratory virus. For one thing, it would be easier to administer. Oral polio vaccines, for example, can be given by volunteers with no medical credentials. Also, by stopping the virus in the respiratory system, it might have greater efficacy. Further, as the authors write: “Mucosal immunity induced by intranasal vaccination with an influenza vaccine is more effective and cross-protective against heterologous virus infection than systemic immunity induced by parenteral vaccines.”
Intranasal vaccination induces the nasal IgA antibody, which is protective against respiratory viruses, such as influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, the researchers write: “Understanding how mucosal immune responses are elicited following viral infection is important for developing better vaccines.”
In the new study, Ichinohe and colleagues treated mice intranasally with an antibiotic cocktail to kill bacteria before influenza virus infection.
The researchers found that disruption of nasal bacteria by antibiotics before influenza virus infection enhanced the virus-specific antibody responses. “We found that intranasal application of antibiotics (to kill nasal bacteria) could release bacterial pathogen-associated molecular patterns (PAMP), which are bacterial components that stimulate innate immunity that act as mucosal adjuvants for influenza virus-specific antibodies response,” said Ichinohe.
Innate immunity, which is not specific to a particular pathogen, is the first line of defense against non-self 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 for 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 while the upper respiratory tract contained commensal bacteria, relative amounts of culturable commensal bacteria in nasal mucosal surface were significantly lower than that in the oral cavity. The researchers tested whether intranasal supplementation of cultured oral bacteria enhances antibody responses to intranasally administered vaccine and found that oral bacteria combined with intranasal vaccine increased antibody responses to intranasally administered vaccine.
Ichinohe said the findings provide clues to developing better intranasal vaccines. “We wish to develop effective intranasal vaccines for influenza and COVID-19 in the near future,” he added.
