Notes from the Medical Director

Dr. Kristen Feemster is the Medical Director of the Philadelphia Department of Public Health’s Immunization Program.

The return of the flu spray: what changed?

For the 2018-19 flu season, the Advisory Committee on Immunization Practices (ACIP) added the intranasal live-attenuated influenza vaccine (LAIV) back to the list of recommended flu vaccines for children and adults. The LAIV is a flu vaccine given as a nasal spray instead of as a shot – which a lot of patients liked.

LAIV, the flu spray, was fist introduced in 2003. It initially appeared to work really well in children, so in 2014, the ACIP made a recommendation to prefer it. But 2 years later, they changed their minds, recommending against it for the past few seasons because of LAIV’s poor effectiveness.

So what changed? Why is it being reintroduced now? Let’s take a deeper dive.

How is LAIV different from other flu vaccines?

Most flu vaccines are “inactived influenza vaccines,” or IIVs. These are made by growing the flu virus in eggs, purifying it, and then inactivating the virus – killing it. It’s then given as a shot that teaches our immune system how to respond to an actual live flu virus – even though the IIV can’t reproduce to cause a flu infection.

We’ve been using this method to make flu vaccines since the 1940s. Since the flu virus changes each year, we have to make a new vaccine each year so that the vaccine matches up with the flu strain that’s likely to emerge most strongly each year.

• IIV: inactivated virus, given with a shot
• LAIV: weakened virus, given with a nasal spray

Unlike the IIV, the LAIV (live attenuated influenza vaccine) is made by growing the flu virus in egg cells, and then just weakening it instead of inactivating the virus. It’s then given as a nasal spray instead of a shot – and the weakened virus can reproduce just enough to spark an immune response in a patient’s body. Though the virus is live, it’s too weak to cause infection; and since it’s administered in the nose – which is how a lot of people are exposed to the flu – it can be an especially effective way to provide protection: following the same path the disease would follow.

So why was the LAIV removed from the list of recommended vaccines in 2016?

When LAIV was first introduced, it did appear to work a little better, especially in children. So in 2014, the ACIP gave LAIV a preferential recommendation – preferring the spray over the shot.

Shortly after that – once the spray was used more widely – the ACIP’s research showed that the spray stopped working as well as it initially did. For 3 years in a row, the spray didn’t perform any better than the shot. In fact, it was less effective. So, while the CDC worked to understand what happened, the ACIP removed their recommendation for the spray (LAIV).

So what happened?

Every flu vaccine protects against 3 to 4 strains of the flu. And, the CDC found that one of the flu strains in the spray didn’t reproduce well enough to spark a good immune response in patients. Since the spray relies on weakened but live virus to reproduce in order to trigger protection in a patient, this was a problem.

This flu strain was H1N1. We had several seasons where a lot of the flu disease was due to H1N1 – so the spray just didn’t provide as much protection as originally hoped.

Okay – so now the spray is back?

Yes. Once the CDC figured out the problem with the spray, the vaccine manufacturer replaced the H1N1 strain – which wasn’t reproducing well – with another strain that works better. They also checked to make sure that there’s a good immune response to the new LAIV.

The ACIP reviewed all of the changes and felt that the problem was addressed – so the spray was added back to the list of recommended flu vaccines for anyone between age 2 and 49.

Even though the ACIP recommends the spray, the American Academy of Pediatrics recommends the shot. Why do they disagree?

When the ACIP reviewed information about the new version of the spray – including studies on the spray’s effectiveness from other countries that continued to use it – they felt that the strong immune response was a good sign that the spray should work at least as well as the shot.

The AAP was also reassured, but they wanted to see more information on protection against the actual disease before they strongly recommended it. So, they decided to recommend the inactivated vaccine (the shot) over LAIV (the spray) until we learn more about the spray’s effectiveness once it’s used more broadly.

So what should I do?

Offer both vaccines.

The effectiveness of the flu vaccine always varies from year to year as researchers try to match the vaccine to the flu virus that they expect to dominate the flu season. Despite varying effectiveness, vaccination is our best method of protection against this virus that kills tens of thousands of people in the USA each year. Since some people decline the flu vaccine because of a fear of injections, having the spray available may increase the likelihood that patients will accept the vaccine.

Patients look to us – health care providers – to listen to their concerns and make recommendations that will keep them healthy. So let’s offer them choices that can help protect them, and let’s remind them that we get our flu vaccines to protect ourselves, our children, our patients, and our community too.

For the 2018-19 flu season, the Advisory Committee on Immunization Practices has added the intranasal live-attenuated influenza vaccine (LAIV) back to the list of recommended flu vaccines for children and adults.  The ACIP recommended against LAIV for the past few seasons because of poor effectiveness.  Why is it being reintroduced now?

How is LAIV different from inactivated influenza vaccines (IIV)? 

Inactivated influenza vaccines are made by growing influenza viruses in eggs, purifying the virus then inactivating, or killing the purified virus.  It is given as a shot and leads to an immune response that will give us protection, but the inactivated virus cannot reproduce to cause infection.  We have been using this method to make flu vaccines since the 1940s. The flu virus changes a little each year so we have to make a  new vaccine to make sure we get a good match.

LAIV is made by growing influenza virus in egg cells then weakening it.  It is given as a nasal spray so that the weakened virus can reproduce just enough to spark an immune response and give us protection, but the live virus is too weak to cause disease.  Because LAIV sparks an immune response in the nose where we are also exposed to influenza, it could be an especially effective way to provide protection

Why was LAIV removed from the list of recommended vaccines in 2016?

When LAIV was first introduced, it did appear to work a little better, especially in children.  So in 2014, the ACIP gave LAIV a preferential recommendation, in other words, the ACIP preferred LAIV over the inactivated vaccine.  But shortly afterwards, when the ACIP noticed that LAIV stopped working well.  For 3 years in a row, LAIV did not perform any better than IIV- in fact it had lower effectiveness.  While the CDC worked to determine why LAIV wasn’t working well, the ACIP removed their recommendation for LAIV.

What happened?

It turned out that one of the flu strains in LAIV (every flu vaccine protects against 3 or 4 strains) did not reproduce well enough to spark a good immune response- so protection was not very good either.  The affected strain was H1N1 and we happened to have flu seasons with a lot of H1N1.

Why is LAIV now available again?

Once the problem with LAIV was recognized, the vaccine manufacturer replaced the H1N1 strain that wasn’t reproducing well with another one that works better.  They also checked to make sure that there is a good immune response to the new LAIV for all of the included strains.  The ACIP reviewed all of this information and felt that the issue was resolved and LAIV was added back to the list of recommended influenza vaccines for anyone between 2 and 49 years of age.

Even though the ACIP has recommended LAIV for 2018-19, I read that the American Academy of Pediatrics still prefers the inactivated vaccine. Why is there a discrepancy?

When the ACIP reviewed information about the new LAIV, they felt that the strong immune response was a good indicator that the vaccine should work at least as well as the inactivated vaccine so should be available for administration.  The ACIP also reviewed studies on LAIV effectiveness from other countries who had continued using LAIV and found these studies to be reassuring.  The AAP was also reassured that the new LAIV leads to a strong immune response, but they wanted to see more information on protection against actual disease before strongly recommending LAIV.  For that reason they decided to recommend a preference for the inactivated vaccine until we learn more about actual LAIV effectiveness.

So what should I do?

The new LAIV addresses the problem that made LAIV show poor effectiveness and leads to a good immune response which is a sign of good protection.  Flu vaccine effectiveness always varies each year due to the match between our vaccines and circulating influenza types- but vaccination is still our best method of protection.  Since the fear of injections is one reason some people decline flu vaccines, availability and use of LAIV may help increase the likelihood that some patients say yes to flu vaccines.

Notes from the Medical Director

Dr. Kristen Feemster is the Medical Director of the Philadelphia Department of Public Health’s Immunization Program.

Is it time for a Lyme vaccine?

The New York Times recently reported what we’ve seen for several years now: that Lyme disease and other tick-borne diseases are spreading.

The US Centers for Disease Control and Prevention (CDC) and the Environmental Protection Agency (EPA) have both observed that Lyme disease has been rising. In fact, since 1990, Lyme disease cases in the USA have tripled.

So what’s going on? Well, climate change is probably a factor. Lyme disease is spread by blacklegged ticks, which are commonly found on deer and white-footed mice. Because of changes in weather patterns, their habitat is expanding – and, milder winters mean that fewer ticks die off each winter.

Health officials are pretty sure that this is only going to get worse. Whether you spend time in city parks or live in wooded areas, it is possible to find blacklegged ticks – and there are things we can do to prevent getting bitten by ticks.

What about a Lyme vaccine?

In 1998, a vaccine for Lyme disease was released. Four years later, the company that made it took it off the market: it just didn’t sell very well. There were concerns that the vaccine could be linked to autoimmune diseases, even though all of the studies about the vaccine found that it was safe. Plus, a lot of health care providers were unclear about who should get the vaccine.

That was several years ago. Now, with Lyme disease on the rise – and expected to continue rising – there are initiatives to develop a new vaccine to prevent Lyme disease and to also potentially prevent other infections spread by ticks. If a vaccine comes to market, then the US Advisory Committee on Immunization Practices (ACIP) would review the evidence and make recommendations about who should get the vaccine, and when.

Lyme disease can be serious – people with the disease can have symptoms that range from a rash to joint swelling to neurologic symptoms. No matter how it presents, Lyme disease is treatable and responds well to antibiotics, but it can sometimes take time for symptoms to go away completely. And while the CDC counts about 30,000 people per year in the USA getting Lyme disease, they’re pretty sure that the actual figure is much higher – up to ten times higher – due to cases not getting properly diagnosed or reported.

This is the time to build up our prevention tool box for Lyme disease. Preventing its spread will take a lot of different strategies: teaching the public to prevent tick bites, developing better insect repellents, and reducing tick habitat around people’s homes. But adding a vaccine to our prevention options could be another powerful tool.