Influenza vaccine ‘desperately’ needs improvement

Print 05 December 2016
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The current seasonal influenza vaccine is not perfect, but experts agree that it remains the best available tool for fighting influenza — at least for now.

“We wish it were better,” CDC Director Thomas R. Frieden, MD, MPH, said during the National Foundation for Infectious Diseases’ annual influenza news conference in Washington, D.C., “but if the match is good, it will cut your risk of flu by at least a half, and that’s far better than anything else you can do to protect yourself.”

Last season's influenza vaccine was 47% effective, according to CDC numbers. Effectiveness was far lower in 2014-2015, however, when the vaccine did not line up as well with circulating influenza viruses. Researchers believe a poor matchup like this can be avoided with a better vaccine, so they have been exploring ways to make one, including taking aim at parts of the virus that are not as susceptible to mutation as the one targeted by current vaccines.

If successful, experts believe a so-called “universal” influenza vaccine could protect patients against all strains of the virus for decades — maybe even a lifetime. It could mean a world without seasonal epidemics and global pandemics of influenza, which remain among the world’s biggest infectious disease threats.

Other experts think the bar should be set lower, but agree that the vaccine needs improvement.

“This is a vaccine that desperately needs to be redone,” Michael T. Osterholm, PhD, MPH, director of the Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota and one of the authors of a 2012 report about the need for better influenza vaccines, told Infectious Disease News. “Influenza is a serious disease that desperately needs to be addressed both from a seasonal flu status and pandemic status.”

Infectious Disease News spoke with several influenza experts about the successes and failures of the vaccine and what can be done to make it better.

Influenza remains biggest threat to public health

The 1918 influenza pandemic killed approximately 50 million people worldwide. If a similar pandemic happened today, more people would die in just a few months than AIDS has killed in 30 years, Osterholm said.

“This should be our public health threat No. 1,” he said. “This is it.”

Influenza pandemics have struck three more times since 1918, the last one occurring in 2009 when a new influenza A (H1N1) “swine flu” replaced the old epidemic “Spanish flu” strain and killed as many as 18,300 people in the United States. Unlike seasonal epidemics, which mainly occur in winter in most parts of the world, pandemics can go on for a year or more and occur when novel animal influenza viruses mutate and begin infecting humans.

Peter Palese, PhD, professor of microbiology and infectious diseases and chair of the department of microbiology, and his colleagues, Florian Krammer, PhD, associate professor in the department of microbiology, and Adolfo Garcia-Sastre, PhD, professor of microbiology and medicine, all in the Icahn School of Medicine at Mount Sinai in New York, have led research into finding a universal influenza vaccine. Palese was the first to genetically map influenza A, B and C viruses, which infect humans, and identified the mechanisms of neuraminidase inhibitors, which are used as antiviral drugs to fight influenza.

In 2005, Palese was part of a research team that reconstructed the 1918 pandemic influenza virus in a lab, providing new information about why it was so virulent and how it killed so many people. Seasonal influenza is deadly as well, killing up to tens of thousands of people in the U.S. in a single year.

“This is why we are spending our lives on it,” Palese said.

Click the image to enlarge.

‘Spotty’ record of current vaccine

The most compelling argument for a better influenza vaccine can be found in the data. Since 2004-2005, the effectiveness of the vaccine has ranged from 10% to 60%, according to the CDC. This means that, during the best year, getting the vaccine decreased a person’s chances of an influenza-related doctor’s visit by 60%.

In 2014-2015, the vaccine’s H3N2 component did not match a majority of the circulating influenza A (H3N2) viruses — the most prevalent subtype — leading to an overall vaccine effectiveness of just 19%, according to researchers. The protection for influenza A (H3N2) was 6%, not statistically different than 0%.

“The current vaccines have an at-best spotty track record for protection and, in fact, may very well end up being not protective at all in many cases,” Osterholm said.

Currently, selecting which viruses will be in the seasonal influenza vaccine is a bit of a guessing game that involves picking strains that research has shown are most likely to circulate. In the Northern Hemisphere, WHO makes its recommendations for the vaccine in February. This year, the FDA adopted WHO’s recommendations unanimously in March for a trivalent vaccine containing two influenza A viruses and one influenza B virus, and a quadrivalent vaccine containing two A and two B viruses. Some seasons, as in 2014-2015, antigenic drift leads to a mismatch between a component in the vaccine and a circulating strain.

Frieden said the current vaccine has been a good match for the viruses that have been seen so far this season, but noted that it is too early to predict what the coming months will bring.

“Flu is unpredictable,” he said. “We know there’ll be a season, but when it is and which flu strain predominates, only time will tell.”

There are two new vaccine choices this season: a four-component influenza shot (Flucelvax Quadrivalent, Seqirus) licensed for use in patients aged 4 years and older that uses virus grown in a cell culture instead of an egg, and a vaccine that includes an adjuvant for adults aged 65 years and older (Fluad, Seqirus). But children between the ages of 2 and 17 years will not have the option of getting the live-attenuated influenza vaccine (LAIV) — offered as the nasal spray FluMist (MedImmune) — after research showed that it was ineffective for the past 3 years. The CDC Advisory Committee on Immunization Practices (ACIP) voted to not recommend its use, raising concerns that vaccination coverage will drop in this age group.

Influenza vaccination coverage among children aged between 6 and 23 months was 75% during the 2015-2016 season, according to the CDC — higher than in any other group. One reason for this is because children that young make more frequent visits to the doctor and have more opportunities to get immunized, according to Patricia Whitley-Williams, MD, division chief and professor of pediatrics in the Robert Wood Johnson Medical School at Rutgers University.

In fact, children aged between 6 and 23 months were the only age group to exceed the national public health goal of 70% coverage. (The CDC noted a concerning decline in vaccination rates for older Americans.) After the ACIP recommended against using the LAIV, manufacturers increased production on the other vaccines, but Frieden said he hoped the spray would be available again soon. Canada and the United Kingdom said they would use the nasal spray vaccine following separate studies showing that it was still effective. Like Frieden, Whitley-Williams lamented the loss of that option in the United States.

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