Friday, November 07, 2014

CDC Statement On LAIV Effectiveness Against H1N1 In 2013-14 Flu Season



# 9296


There’s always a degree of uncertainty heading into every flu season as to whether the flu vaccines – whose strains are selected 6 months in advance – will prove effective throughout the entire season.  Flu viruses mutate over time – and minor strains that seemed insignificant in February can become dominant by November.

Last weekend, in A `Drift’ In A Sea Of Influenza Viruses, I wrote about the rise over the summer in a new clade of H3N2 seasonal flu that differs antigenically from the strain in this fall’s vaccine. 


For now, the vaccine-targeted strain remains more common than this new interloper, but the flu season is just getting started.  The H3N2 strain for next year’s Southern Hemisphere flu shot has already been changed to meet the challenge of this emerging A/Switzerland/9715293/2013 (H3N2)-like virus.  How big of an impact it will have in the Northern Hemisphere this fall and winter is unknown.


The rock of flu stability over the past 5 years has been the H1N1 vaccine strain, which has remained unchanged since it emerged as a pandemic in 2009.  Last year, however, was the first dominant H1N1 flu season since 2009, and the first real test of the H1N1 component in years.


We saw a good deal of severe disease among middle-aged adults last year, and recently a PNAS article suggested this was due to a small mutation in the H1N1 virus (see CIDRAP article Study: Middle-aged adults susceptible to recent flu virus mutation).

Complicating matters, yesterday it was announced that last year’s LAIV (Live Attenuated Influenza Vaccine)  –  aka FluMist nasal spray vaccinewas not effective against the H1N1(pdm) virus in children aged 2-8, and that it is likely to be ineffective this year as well. 


Given its strong performance in previous years, this LAIV failure is a bit of a mystery, and somewhat awkwardly this revelation comes just four months after Federal vaccine advisors voiced a rare preference for the nasal mist vaccine for children (see CIDRAP ACIP cites preference for nasal-spray flu vaccine for young). 


The fact that we are just now learning about this now – this deep into the 2014-15 vaccination season – is likely to raise a lot of questions regarding timely vaccine effectiveness surveillance.  

Late yesterday, the CDC posted a statement addressing these findings.  While clearly a disappointment, they point out that this year is likely to be an H3N2-dominant year, making the LAIV still a reasonable choice for children’s vaccinations, even if the H1N1 component isn’t terribly effective.  


CDC Statement on LAIV Effectiveness and Vaccination of Children

CDC conducts vaccine effectiveness (VE) studies with the U.S. Influenza Vaccine Effectiveness (Flu VE) Network each season to estimate flu vaccine VE. Mid-season VE estimates for the 2013-2014 season were published on February 20, 2014, in a Morbidity and Mortality Weekly Report entitled: "Interim Estimates of 2013-14 Seasonal Influenza Vaccine Effectiveness—United States." Final overall VE estimates were similar to the interim published estimates. However, end of season data evaluated during the summer by the Flu VE Network also allowed separate estimates for the live attenuated influenza vaccine (LAIV, or the "nasal spray vaccine") and inactivated influenza vaccine (IIV or "the flu shot). During 2013-2014 there was no measurable effectiveness for LAIV against influenza A (H1N1) among children enrolled in the study.

While it is well-known that VE can vary by age group, season, circulating influenza viruses and by vaccine, this finding is unexpected and different from some previous studies, which suggested that LAIV may be more effective for younger children. Since 2008, ACIP and CDC have recommended that all children 6 months and older (with rare exceptions) receive influenza vaccine annually, using any licensed age-appropriate vaccine. During the summer of 2014, however, ACIP and CDC recommended that beginning during the 2014-2015 influenza season, LAIV should be used for healthy children 2 through 8 years of age when immediately available and when there are no contraindications or precautions against getting that vaccine. This decision was based on previous data showing that LAIV offered superior protection against influenza virus infection compared to IIV in young children.

The reasons behind the lack of effectiveness against H1N1infections for LAIV during the 2013-14 season are not fully understood. It is possible that results may be specific to the H1N1 component of LAIV. Influenza H1N1 viruses predominated during the 2013-2014 season for the first time since their emergence in 2009 when they caused a pandemic. It also is possible – though less likely – that there is an unidentified issue with the study methods or analysis plan.

CDC is working with ACIP and other partners to collect more information to better understand these data and to determine what actions might be appropriate.

2014-2015 Season

The 2013-2014 season LAIV VE estimates against H1N1 for children suggest that LAIV may not protect against H1N1 viruses during the 2014-2015 season because the same H1N1 vaccine virus from 2013-2014 is included in the 2014-2015 vaccine. All LAIV is designed to protect against four different influenza viruses: Influenza A (H1N1), A (H3N2) and two influenza B viruses.

CDC has been monitoring surveillance data closely. So far, U.S. seasonal surveillance data as reported in FluView indicate substantially greater circulation of H3N2 and B viruses and little circulation of H1N1 viruses. (Of the subtyped viruses reported to CDC from the week ending October 5 through the week ending October 25, 2014, 387 (31%) have been H3N2 viruses, 387 (31%) have been influenza B viruses and 16 (1%) have been H1N1 viruses. Another 466 influenza A viruses were not subtyped.)

In addition, some of the influenza A (H3N2) viruses have been drifted from the H3N2 vaccine virus used in this season’s vaccine. (An October 3 Morbidity and Mortality Weekly Report "Influenza Update" reported that CDC antigenically characterized 391 viruses collected worldwide during May 18 through September 20, 2014, including 70 A (H1N1) viruses, 141 influenza A (H3N2) viruses, and 180 influenza B viruses. Of the 141 influenza A (H3N2) viruses characterized 69 (49%) were antigenically similar to A/Texas/50/2012, the influenza A (H3N2) component of the 2014-2015 influenza vaccine for the Northern Hemisphere. Only 10 A (H3N2) viruses collected in the United States since October 1 have been characterized so far this season. Seven of these (70%) are like the A (H3N2) vaccine virus, 3 (30%) have been characterized as A/Switzerland/9715293/2013, an antigenic variant virus which has been selected for the 2015 Southern Hemisphere influenza vaccine.) It is important to note that there are some data to suggest that LAIV may offer better protection than IIV against antigenically drifted viruses.

As of October 31, manufacturers reported having distributed more than 132 million doses of the 151 million to 156 million total doses projected to be available for the U.S. market this season. (The manufacturer of LAIV projected that as many as 18 million doses of LAIV would be produced for the U.S. market this season.) Vaccine uptake data for this season are not yet available, however, past trends suggest that more than half of flu vaccines given to children are administered by the end of October, suggesting that many children may have already gotten vaccinated.


1. Surveillance shows that there is substantially more circulation of influenza A (H3N2) and B viruses and very little circulating H1N1 so far;

2. LAIV has been shown to offer good protection against influenza A (H3N2) and influenza B viruses in the past;

3. LAIV may offer better protection than IIV against antigenically drifted viruses that may circulate this season; and,

4. Vaccine providers have received their vaccine for the 2014-2015 season and have likely administered a good proportion of it;

ACIP and CDC have not changed the current influenza vaccination recommendations.

People who have not been vaccinated yet this season should get vaccinated now. Parents should seek to get their children immunized with whatever vaccine is immediately available and indicated. Influenza vaccination should not be delayed to procure a specific vaccine preparation. The HealthMap Vaccine Finder can be used to locate vaccine.

CDC is in discussions with the manufacturer of LAIV, the Department of Defense, the Food and Drug Administration, and other partners to better understand the data from last season, and to determine causes and ways to address the low VE of LAIV against H1N1. For the current season, the U.S. Flu VE Network has expanded enrollment of children and will continue ongoing studies of serologic outcomes after vaccination in children getting IIV and LAIV. This additional data collected during 2014-2015 will help inform discussion about this matter further.


D Leith said...

Michael, as ever I find your blog informative and remain a regular reader. I have a couple of vaccine related questions that maybe you or another reader could answer.

First, from your posts it appears that the flu vaccine components often remain unchanged from season to season. In this case, if my son got the standard flu shot last year, and the nasal mist this year, would he likely be protected against H1N1? How long does the protection against individual clades typically last (for those for whom it worked at all)?

Second, I understand that the CDC recommends vaccine makers target the top 3 likely strains for any given year (2 A types and a B type). But for those of us who get a shot every year (admittedly a subset of the whole population) wouldn't more diversity in targets offer more protection - provided the protection lasted longer than a single season?

Michael Coston said...

D Leith,

You raise some interesting questions. While I'm hardly an expert, and I can only talk in generalities, I'll take a stab at it.

First, the longevity of antibody protection seems to vary both by the sub-type of flu involved and an individuals previous exposures to similar strains either via vaccine or infection and by the individual.

Older vaccine recipients generally see vaccine effectiveness wane quicker. But there are other variables as well.

There has been talk of adding `primer' strains to seasonal flu shots for years (ie in anticipation of the return of H2N2, or for H5 or H7 strains), but the logistics involved in producing a wide range of vaccines with today's technology makes that very difficult. See:

There is also a lot we don't understand about how OAS (Original Antigenic Sin)& ADE (Antigenic Dependent Enhancement) affect influenza susceptibility and pathogenesis, making bold vaccine moves a bit of a gamble.

For more on that, you might want to revisit: