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A summary of presentations from the weekly Summit partner webinars

December 7, 2023 – The latest Summit Summary

Respiratory Virus Surveillance Update – Katie Tastad (CDC)

Katie Tastad, PhD, MPH, Influenza Division – Domestic Surveillance Team, CDC, gave an update on respiratory virus surveillance for week 47, ending November 25.

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Outpatient Respiratory Illness (See: FluView)

  • Influenza-like Illness (ILI), fever plus cough or sore throat
    • Continuing to increase
    • Above national baseline for the last four weeks
  • ILI by age
    • Trending upwards for age group 0–4 years and age group  5–24 years

Outpatient Respiratory Illness Activity by Jurisdiction

  • Activity earliest in the southeast and south-central parts of the country
  • Some increases in the mountain states and upper Midwest

Virologic surveillance

  • Clinical labs
    • Percent of specimens tested in clinical labs has been increasing steadily for the past few weeks
    • Increases in both influenza A and B
  • Public health labs
    • 80% influenza A, mostly H1N1
    • 20% influenza B

Influenza-positive Tests Reported to CDC by Public Health Laboratories and ILI Activity by HHS Region for 2023–2024 Season

  • Southeastern and south-central regions have had a greater proportion of B viruses than the rest of the country
  • All reported B viruses have been Victoria lineage

Hospitalization

  • Continuing to increase
  • FluServ-Net shows weekly rate is remaining low but increasing
    • Far below this point last season

Mortality

  • Starting to see an upward trend in mortality
  • Pediatric deaths have been reported, occurring predominately in southeast and south-central regions
    • Eight reported pediatric deaths so far this season
    • Mix of influenza A and B viruses

Summary

  • Influenza activity continues to increase in most parts of the country
    • Most notably in south-central, southeast, mountain, and west coast regions
  • Influenza A(H1N1) is still the most frequently detected, although influenza B is also being detected
  • CDC estimates that there have been at least 1.8 million illnesses, 17,000 hospitalizations, and 1,100 deaths from flu so far this season 

Resources

For questions, contact Katie Tastad at qwu5@cdc.gov.

Questions

 Q: Do you have any ideas about how to best get the word out about the increase in disease activity?

Katie Tastad (CDC): I think it is a little bit of an early season, not as early as last year last year was, but I think that is a little bit of a motivator especially as we’re getting to the holiday season. If people have it on their to-do list, I think it’s a good idea to push vaccine messages now because everything is starting to increase. We already have had almost 2 million illnesses; that’s a lot.

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Dealing With the End of B/Yamagata Transmission – Arnold Monto (University of Michigan)

Arnold Monto, MD, Thomas Francis Professor Emeritus in the Department of Epidemiology, School of Public Health, University of Michigan (U-M), gave a presentation on dealing with the end of B/Yamagata transmission.

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Influenza B viruses

  • Influenza B viruses circulate globally every year; influenza B viruses drift, but do not shift
  • Two lineages of influenza B viruses have circulated
    • B/Yamagata
    • B/Victoria
  • The two lineages are very distinct
  • Children have higher rates of infection with influenza B compared to adults
  • Although fewer deaths and complications than influenza A (H3N2) virus, influenza B still leads to severe complications in all age groups
  • During the 1990s, B/Yamagata was the only B virus that was detected
  • In 2000s, B/Victoria detected and both lineages co-circulated

Options in an era of excess capacity

  • Starting around 2010, there was a discussion on whether both lineages of type B should be put in flu vaccines
    • Pro:
      • Prevention of morbidity and mortality with influenza B
      • Sufficient manufacturing capacity for public health benefit
      • Public and provider enthusiasm
    • Con:
      • Public health benefit might be modest
      • Increased costs
      • More data needed
    • Decision made to go to quadrivalent from trivalent
    • Found to be a benefit to a second strain in the vaccine probably mostly in children

Vaccine Effectiveness Study

SEE: D. Shasha, et. Al.: Quadrivalent Versus Trivalent Influenza Vaccine: Clinical Outcomes in Two Influenza Seasons, Historical Cohort Study

  • Showed there wasn’t much of a benefit in terms of having B strain
  • Showed that in the years in which there was a vaccine mismatch, there wasn’t a whole lot of difference between the B having the right or wrong strain in the vaccine
  • But benefits most likely for children

U.S. Flu VE Network: Five Study Sites and Principal Investigators

  • The current U.S. Flu Vaccine Efficacy Network consists of five study sites across the U.S.
    • A multi-year study conducted by this network found no real advantage in having quadrivalent vaccine used over trivalent
    • Don’t have sufficient numbers in young children to be able to say there might be a benefit for children, however

U.S. Flu VE Network 2011–12 Season: Crude and Adjusted VE by Influenza Type for all Ages

  • Since most respiratory viruses went away for a short time during the pandemic, the only B strain that has not re-emerged is B/Yamagata
  • Concern about the theoretical potential for B/Yamagata to re-emerge, since live, could possibly results in a reassortant
  • If going to remove B/Yamagata strain, should remove from all influenza vaccines all and not just the live vaccine
  • Continuing to give the B strain bothered members of VRBPAC
    • Why give the B strain when it has not been around for a significant period of time?
    • Current B/Vic strain in the vaccine is a 2013 strain.

Reference: SEE: M. Gaglani, et. Al.: Effectiveness of Trivalent and Quadrivalent Inactivated Vaccines against Influenza B in the United States, 2011–2012 to 2016–2017

VRBPAC meeting in March 2023 for current northern hemisphere formulation

  • Concern giving unnecessary antigen in the vaccine
  • Nothing could be done this current season because manufacturers have been on speculation producing B strain in the vaccine
  • The B/Yamagata in the vaccine now is the 2013 strain because that was the last time the vaccine was updated
  • Meeting in July 2023 by European regulatory agencies in London – also had discussion to recommend the B/Yamagata strain be eliminated from the vaccine
    • Discussions ongoing

March 17, 2023 meeting of VRBPAC for approval of southern hemisphere formulation

  • Discussion about B/Yamagata component of the vaccine
  • Voting question: Does the committee recommend excluding the Yamagata lineage from the vaccine as soon as possible?
    • Hope this to be possible by next year strain selection in February/March
  • For 2024 formulation, committee recommended that B/Yamagata be included if there was a need to include it as a B strain component
  • Issues discussed
    • o couldput more H3N2 antigen in each dose when the B/Yam is removed which would make it a semi high dose vaccine for the H3N2 component
      • Would be considered a new vaccine
      • Would require at least immunologic clinical trials
    • Could possibly add a second H3N2 strain instead of more of the strain that’s already included
  • Right now goal is to eliminate the B/Yamagata from the vaccine 

Summary

  • Historically, the prediction of the B lineage was poor and vaccine protection sub-optimal with mis-match of the vaccine with circulating B strains
  • Might not be a need for quadrivalent vaccine
    • Some supportive data
    • May be a need for children with no experience with exposure to both lineages
  • View is that removal of B/Yamagata from vaccine should be tied to a change in the formulation of the vaccine
    • Considered by regulators to be a new vaccine and needs clinical data before approval
Questions

Q: Can you explain the manufacturing process and logistics that would entail waiting this season and another season in the northern hemisphere and southern hemisphere before a change could be made?

Arnold Monto (U-M): For several years, WHO has been recommending two formulations a year. WHO meets in February each year to make the recommendations for the subsequent northern hemisphere for the vaccine season starting in September. They also meet in September/October for a southern hemisphere formulation vaccine strain decision. What is going on now is that FDA is involved in the southern hemisphere formulation because a few manufacturers are producing southern hemisphere vaccine. The manufactures making southern hemisphere vaccine in the U.S. have to have FDA approval of the vaccine in the US, even though it’s not administered in the United States. So, we had to look at the southern hemisphere formulation, and we had hoped that it might be possible to move ahead and get the B/Yamagata out of the southern hemisphere formation for 2024. That was not feasible because as with the northern hemisphere formulation, it takes a while to get it produced, bottled, and distributed.

What we are hoping is that the northern hemisphere formulation for this coming year in 2024–2025 will not have B/Yamagata in it. A meeting will take place in February at WHO and in March at the FDA. The problem with all this is more of a regulatory problem than anything else because influenza vaccines are a global commodity and in every country. Every country or group of countries has to approve the vaccine formulation. The licenses for the old trivalent vaccine in many countries have lapsed and the way they are producing them is updated and improved from the way they used to produce them. So, there’s a lot of manufacturing protocols that have to be updated. The problem in preventing moving more quickly is regulatory. The biggest problems now are regulatory in all countries that use or manufacture influenza vaccine and logistic issues.  The other thing is a question of how many eggs they’ve ordered and things like that because this means they’re producing less antigen for each vaccine dose. That’s why the hope was it could be done a little more smoothly, replacing the extra B with some extra H3N2. That was the something I had hoped was going to be possible, because H3N2 is the one strain that usually gives us a lower effectiveness. We need better effectiveness of H3N2.

 

Q: Can you give us some more historical background on studies that showed there was not much of an advantage two B lineages over single lineages? Why did we move to quadrivalent influenza vaccines initially?

Arnold Monto (U-M): Given the limitation of time, I didn’t mention studies that were done in young children which showedmore benefit for children. There is cross-protection between the 2 lineages, but younger people might not have had experience with both lineages. There were studies that were done which showed there was an advantage in having both lineages in the vaccine. The reason I mentioned all this is the downside of eliminating the B/Yamagata because when you have something as tricky as flu strain selection and you’re eliminating something, the downside of eliminating B/Yamagata is that there is a possibility it’s been transmitting someplace where there isn’t good surveillance. But, with  surveillance now done globally, there’s very little chance that B/Yamagata is being missed. So, there is little downside in eliminating B/Yamagata, and the upside is not giving an antigen  for which you do not have a need.

Carolyn Bridges (Immunize.org): You mentioned the downside to some of the challenging regulatory issues.  If we move back to a trivalent and there is an emergence of a new lineage of B or A, it would be more difficult to go back to a quadrivalent vaccine?

Arnold Monto (U-M): The capacity to produce a different kind of quadrivalent vaccine will still be there.  If we continue to produce B/Yamagata, its’s still the 2013 virus.  So, even if we are missing the B/Yamagata and if it comes back, we’d have to have another B/Yamagata in the vaccine. That could be dealt with as we usually deal with a new strain coming along. Therefore, it’s been decided that the elimination is the best approach right now since we have been talking about this for several years now.

We had hoped it would be a quicker  shift to trivalent but that hasn’t happened because much of this work to change the vaccines has to originate from the manufacturers and what the manufacturers are working on is more advanced kinds of  influenza vaccines. There are a lot of experimental approaches to influenza vaccines which will have broader immunity and better efficacy, which is what we really would like to see. This would be a much bigger change in terms of introducing this to the public. It’s a relatively minor issue to remove a B strain, but because of regulatory and logistic issues, it’s challenging for manufacturers  in terms needing some considerable lead time in getting regulatory approvals and producing the vaccines. I think most people aren’t aware that the vaccine manufacturers often start before the strain selection because they need the time to produce what they believe is going to be in the vaccine, and that’s something that happens at risk. They’ve ordered the components they need for the production even before strain selection and that’s part of the issue.

I think the biggest concern is the quadrivalent vaccine was introduced as something which was filling a gap, and it probably did do some good in younger individuals. It was hard to show because when you do flu effectiveness studies, the confidence intervals are often large, and to say something is an improvement is sometimes hard to demonstrate. When it comes to the idea of having something in the vaccine which is against a component that is no longer circulating, that could be a problem and probably a bigger problem in terms of trying to say that we’re using a relevant vaccine.

 

Q: Do you think that removing B/Yamagata would be as big of an issue if we did not have it in a live attenuated vaccine?

Arnold Monto (U-M): It would not be as much of an issue, but what is happening is there are still B/Yamagata detections and the B/Yamagata detections are sequenced and found to be part of live attenuated vaccine. This does show you that it is getting out there and if there’s any major worry, it’s that you don’t want to be using anything in the live vaccine that you don’t need in the live vaccine. So yes. That is the part of the concern, and it has been pretty well decided that it would be best to do this all synchronously, if not in all countries. At the same time, it raises much fewer issues than not doing it synchronous.

 

Q: When the live attenuated vaccine was first licensed in those first few years we had a number of studies, like in a daycare centers, looking for transmission of the live vaccine. They found no transmission to unvaccinated children from vaccinated children. So, in terms of concern about live vaccine, is that mostly a theoretical concern?  Are the detections you mention all from recently vaccinated people?

Arnold Monto (U-M): Yes, It’s much more of a theoretical concern.  I am not aware of vaccine viruses being identified from anyone other than someone that was recently vaccinated.  And interestingly, it’s usually the Bs that are identified from recently vaccinated individuals.  No vaccine viruses have been identified as circulating viruses in surveillance.

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Announcements
  • There will be an upcoming webinar on adult immunizations and rural health; watch for more information
  • org has a new streamlined look! Please feel free to give feedback: www.immunize.org/about/org/contact.
  • The Summit held a workshop on August 2nd to develop tools to address challenges in providing multiple adult vaccines along with COVID-19, flu, and RSV vaccines. Tools that address billing and insurance issues that go along with vaccinating patients were also developed. See the Summit’s Operationalizing Adult Immunizations in the 2023 Fall Season and Beyond Workshop web page for the deliverables. Note: some deliverables are in process of being finalized and uploaded to the website so check back for more.
  • If you are registered for the Summit not getting the emails from Mailchimp, please add “NAIIS” at info@izsummitpartners.org to your contact list
  • If you have any agenda items that you are interested in sharing with the Summit, please let us know and we can add you to an upcoming call as a speaker or panelist. Contact information: info@izsummitpartners.org

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