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  1. Science & Research (Biologics)

Universal influenza vaccine candidate reduces transmission of virus best when given nasally in mice

Scientists at the U.S. Food and Drug Administration (FDA) have been studying an influenza vaccine candidate that is based on conserved antigens instead, and in animal models protects broadly against widely divergent influenza virus strains. It does not require matching. The scientists have now demonstrated the ability of this universal influenza vaccine candidate to reduce the transmission of influenza virus in mice, even though this vaccine does not completely block infection by the virus.

The FDA findings are important because they suggest the vaccine could both protect recipients and reduce transmission -- even when virus strains emerge with differing envelope proteins, a type of change, that when it occurs, can make existing influenza vaccines less effective.

The key to the FDA universal vaccine is the choice of viral proteins it targets. Current vaccines are designed to trigger production of neutralizing antibodies (antibodies that prevent virus from getting into cells) against proteins on the surface of the virus, mainly a protein called HA. A limitation of such vaccines is that HA mutates frequently, allowing the virus to escape from immunity to an HA-based vaccine.

The candidate vaccine targets two influenza A proteins, A/NP and M2, that do not change from year to year. Unlike seasonal influenza vaccines that induce neutralizing antibodies to HA, immunity to NP and M2 might permit some mild, brief infection. That has led some experts to suggest that this type of vaccine would allow continued spread of influenza viruses to other individuals. However, the new findings show that even without triggering production of neutralizing antibodies, this universal vaccine reduces virus transmission in mice.

In the current study, scientists showed that the vaccine is more effective at reducing transmission of influenza A viruses among mice when it is given intranasally rather than injected intramuscularly. In addition, they showed that the combination of A/NP and M2 is more effective at reducing transmission than either component alone.

This reduction in transmission occurred when the mice were in contact with each other in a cage, and also when the virus was airborne, that is, spreading to uninfected mice who were separated from infected mice by a perforated barrier.

The FDA scientists also showed that immunizing uninfected mice against A/NP and M2 prevented about half of the mice from becoming infected when in direct contact with infected mice.

The new findings also support those of a mathematical model of influenza virus transmission that was developed by scientists at Princeton University with collaboration of the FDA scientists. That model suggested that a vaccine reducing transmission, even if it did not completely prevent infection, could reduce the size of outbreaks and slow the rate of mutation of the virus.

As an example of the type of public health gap to be filled, the 2009 H1N1 influenza virus that caused a pandemic, emerged suddenly. The pandemic influenza strain was identified in April 2009 and by September 2009, the vaccine was developed and produced, and FDA had approved influenza vaccines from various manufacturers for use by the public. While this timeline is considered rather quick with respect to influenza vaccine development and production, it was not available for use as quickly as it was needed. Pandemics are worldwide outbreaks of an infectious disease.

A vaccine that instead protects against all strains (universal vaccine) could be available off-the-shelf as soon as a pandemic emerges. Such a vaccine might reduce the number of illnesses and deaths until a vaccine matched to the new virus is developed and distributed. This approach would need to be tested in humans.

Title
Reduction of influenza virus transmission from mice immunized against conserved viral antigens is influenced by route of immunization and choice of vaccine antigen

Vaccine 36 (2018) 49110-4918
https://doi.org/10.1016/j.vaccine.2018.06.051

Authors
Graeme E. Price*, Chia-Yun Lo, Julia A. Misplon, Suzanne L. Epstein

Division of Cellular and Gene Therapies, Office of Tissues and Advanced Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA

*Corresponding author Graeme.price@fda.hhs.gov