New findings support decision not to use FluMist vaccine
Findings published Wednesday in The New England Journal of Medicine supported federal recommendations that the FluMist Quadrivalent influenza vaccine not be used on patients in the United States.
Delivered as a nasal spray, FluMist Quadrivalent (MedImmune) is preferred by some parents and children over injectable influenza vaccines. However, the CDC’s Advisory Committee on Immunization Practices (ACIP) voted last year not to make the spray available in the U.S. for the 2016-2017 influenza season because studies showed that it was ineffective at protecting patients against the 2009 pandemic strain of the virus, known as influenza A(H1N1)pdm09.
In June, the ACIP again voted that the nasal spray should not be used in 2017-2018, saying it expected new data on the vaccine to be available in the fall. At issue is the unusual finding that the nasal spray, despite containing live-attenuated influenza virus, has not generated protection in patients the way that the injectable vaccines containing killed virus have.
“The simple explanation is that the vaccine virus in the live vaccine didn’t work the way it should have worked, whereas in the inactivated vaccine, that same virus worked well against the circulating viruses,” Brendan Flannery, PhD, epidemiologist in the CDC’s Influenza Division and one of the authors of the new study, told Infectious Disease News. “When the virus was killed in the inactivated vaccine, it worked. When it was a live vaccine, that live virus didn’t perform like a live virus. Something happened.”
The findings published Wednesday were from a study of vaccine effectiveness during the 2015-2016 influenza season, the last time the nasal spray vaccine was available to patients in the U.S. The spray continues to be used in other countries — including Canada, Finland and the United Kingdom — and findings from other studies have showed it to be effective, for reasons that are unclear, Flannery and colleagues said.
For their study, they enrolled nearly 6,900 patients aged 6 months or older who presented with acute respiratory illness at ambulatory health care clinics in the U.S. Approximately 19% of the study participants tested positive for influenza, mostly for A(H1N1)pdm09, which was the most common strain that season.
Overall vaccine effectiveness was 48% (95% CI, 41 to 55), according to Flannery and colleagues. The inactivated vaccine was 60% effective in children aged 2 to 17 years (95% CI, 47 to 70). However, among children, the risk of influenza was not significantly lower in patients who received the nasal spray vaccine than in those who were not vaccinated at all. Specifically, Flannery and colleagues said the spray had a vaccine efficacy of just 5% in this group (95% CI, –47 to 39). Most significantly, its efficacy against A(H1N1)pdm09 was calculated as –19% (95% CI, –113 to 33), compared with 63% for the inactivated vaccine.
This does not mean children who received the nasal spray vaccine were likelier to get influenza than those who were not vaccinated at all, just that there was “no clear benefit” in receiving it, Flannery explained.
“For us biologically, it doesn’t make sense that there’d be increased flu if the vaccine didn’t work; it’s more likely that the vaccine just didn’t provide any protection,” he said.
The revelation that the nasal spray was not working contrasted with previous findings showing it performed better than vaccines containing killed virus, according to Flannery. Live-attenuated vaccines are supposed to reproduce the immune system response of a natural infection.
“There were several studies that showed that it was actually better for young kids and had a better immune response,” he said. “So this is an unusual finding.”
MedImmune, a subsidiary of AstraZeneca, has been trying to determine why the nasal spray no longer works as intended. Last year, researchers from the company said they evaluated several potential causes — including vaccine-virus interference, the effect of pre-existing immunity from previous influenza vaccinations and poor thermostability of A(H1N1)pdm09 strains. They concluded that the most likely cause was reduced replicative fitness of two influenza A(H1N1)pdm09 strains used in the vaccine.
Flannery said the company is working on making a better strain to use in the vaccine. A spokeswoman for AstraZeneca did not immediately return a message seeking comment on the company’s efforts to improve the vaccine.
Flannery said it was important to highlight the data about the nasal spray but said there were other notable findings in the study.
“The most important thing for clinicians is that the shot worked against H1N1 and is a good option,” he said.
Because the nasal spray is not being offered in the U.S., future recommendations on its use may be based on laboratory data from the vaccine’s manufacturer — including assays using ferrets and human cells — and data from countries that continue to use it, Flannery said.
“[Having it] in the armamentarium is really important. It’s one of the tools that helps us to encourage people to get vaccinated every year and we want to make sure that it’s providing protection that is equal to inactivated vaccine,” he said. – by Gerard Gallagher
Disclosures: Flannery reports no relevant financial disclosures. Please see the full study for a list of all authors’ relevant financial disclosures.