Genetic mutation in FluMist could be altered to restore effectiveness

Johns Hopkins University researchers said they discovered a genetic mutation in the nasal spray influenza vaccine that could be altered to restore the vaccine’s effectiveness.

Preferred by some parents and children as an alternative to getting a shot, FluMist Quadrivalent (MedImmune) has not been recommended for use in the United States for the past two influenza seasons after data showed it had lost effectiveness against 2009 pandemic strains of the virus. Unusually, despite containing live-attenuated influenza virus (LAIV), the nasal spray was not generating protection on the same level as injectable vaccines that contain killed virus, U.S. data showed.

Experts were surprised by the findings. Confounding the issue, several other countries continue to use the LAIV considering their own data showing that it has not lost effectiveness. But findings published in The New England Journal of Medicine in August backed up the decision by the CDC’s Advisory Committee on Immunization Practices not to recommend the LAIV in the U.S. 2 years in a row.

Brendan Flannery

“The simple explanation is that the vaccine virus in the live vaccine didn’t work the way it should have worked,” CDC epidemiologist Brendan Flannery, PhD, previously told Infectious Disease News.

In a new study published in Vaccine, Andrew S. Pekosz, PhD, professor in the department of molecular microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health, and colleagues report finding that two of the four virus strains used in the LAIV had a previously overlooked mutation that reduces viral production. When they reversed the mutation in one strain, the virus replicated to higher titers and with faster kinetics in cultured human nasal epithelial cells.

“Only one component of FluMist — the one targeting the type A(H1N1) virus — has been failing in the U.S. recently,” Pekosz said in a news release. “It’s not clear exactly why it has failed but this mutation we identified could be used to make that component of the vaccine a little stronger, thereby improving vaccine efficacy. We now see the possibility of altering this mutation and perhaps others in the vaccine to optimize the vaccine’s protective effect, perhaps for different age groups.”

A spokeswoman for AstraZeneca, which owns MedImmune, said the company is aware of the findings but was not involved in the research and would have no further comment on the results.

“We look forward to reviewing the research and defer to the investigators of this study on any questions regarding scientific insights it may provide,” the spokeswoman, Abigail Bozarth, told Infectious Disease News.

AstraZeneca is conducting a clinical study evaluating the performance of an LAIV containing a new influenza A(H1N1) strain (Slovenia) compared with an old strain associated with reduced effectiveness (Bolivia) in children aged 24 to 48 months. Bozarth said data from that study would be available soon and made available to the CDC. – by Gerard Gallagher

Reference:

Wohlgemuth N, et al. Vaccine. 2017;doi:10.1016/j.vaccine.2017.10.018.

Disclosures: The authors report no relevant financial disclosures. Bozarth is employed by AstraZeneca.

Johns Hopkins University researchers said they discovered a genetic mutation in the nasal spray influenza vaccine that could be altered to restore the vaccine’s effectiveness.

Preferred by some parents and children as an alternative to getting a shot, FluMist Quadrivalent (MedImmune) has not been recommended for use in the United States for the past two influenza seasons after data showed it had lost effectiveness against 2009 pandemic strains of the virus. Unusually, despite containing live-attenuated influenza virus (LAIV), the nasal spray was not generating protection on the same level as injectable vaccines that contain killed virus, U.S. data showed.

Experts were surprised by the findings. Confounding the issue, several other countries continue to use the LAIV considering their own data showing that it has not lost effectiveness. But findings published in The New England Journal of Medicine in August backed up the decision by the CDC’s Advisory Committee on Immunization Practices not to recommend the LAIV in the U.S. 2 years in a row.

Brendan Flannery

“The simple explanation is that the vaccine virus in the live vaccine didn’t work the way it should have worked,” CDC epidemiologist Brendan Flannery, PhD, previously told Infectious Disease News.

In a new study published in Vaccine, Andrew S. Pekosz, PhD, professor in the department of molecular microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health, and colleagues report finding that two of the four virus strains used in the LAIV had a previously overlooked mutation that reduces viral production. When they reversed the mutation in one strain, the virus replicated to higher titers and with faster kinetics in cultured human nasal epithelial cells.

“Only one component of FluMist — the one targeting the type A(H1N1) virus — has been failing in the U.S. recently,” Pekosz said in a news release. “It’s not clear exactly why it has failed but this mutation we identified could be used to make that component of the vaccine a little stronger, thereby improving vaccine efficacy. We now see the possibility of altering this mutation and perhaps others in the vaccine to optimize the vaccine’s protective effect, perhaps for different age groups.”

A spokeswoman for AstraZeneca, which owns MedImmune, said the company is aware of the findings but was not involved in the research and would have no further comment on the results.

“We look forward to reviewing the research and defer to the investigators of this study on any questions regarding scientific insights it may provide,” the spokeswoman, Abigail Bozarth, told Infectious Disease News.

AstraZeneca is conducting a clinical study evaluating the performance of an LAIV containing a new influenza A(H1N1) strain (Slovenia) compared with an old strain associated with reduced effectiveness (Bolivia) in children aged 24 to 48 months. Bozarth said data from that study would be available soon and made available to the CDC. – by Gerard Gallagher

Reference:

Wohlgemuth N, et al. Vaccine. 2017;doi:10.1016/j.vaccine.2017.10.018.

Disclosures: The authors report no relevant financial disclosures. Bozarth is employed by AstraZeneca.