The Need for a Supplemental Influenza Vaccination

Dr. Redfield from the CDC, Canadian authorities and the World Health Organization have stated that the coming influenza season will complicate a new wave of COVID-19 because of the symptom overlap.

“The Public Health Agency of Canada is planning ahead for potential simultaneous outbreaks of the flu and COVID-19,” said spokesperson Geoffroy Levauglt-Thivierge. The worry is if COVID-19 surges at a time that hospitals are already at their busiest, it will break the hospitalization system.

Why not plan on a 2nd (supplemental) seasonal influenza vaccine?

The gist:
  1. The efficacy of the seasonal influenza vaccine has trended downward over the past 25 years.

    It is logical to surmise that the 2020-2021 seasonal influenza vaccine will have an efficacy lower than we need it to be. The reason for the low efficacy is that we are guessing what the prevailing strains will be WAY TOO FAR IN ADVANCE. The vaccine that will be administered this August was determined in February. The problem is that viruses mutate and so do vaccines, as they are being grown in eggs.

  2. Continuing the downward trend, the 2019-2020 seasonal influenza vaccine was not particularly effective for all age groups:
    • Children 6 months – 17 years: 55% effective
    • Adults 18-49 years: 25% effective
    • Adults 50+ years: 43% effective

  3. There is a precedent for supplemental influenza vaccines:
    • In 1976, there was the “Swine Flu Vaccination”, although this was generally regarded as a failure because the spread was not as dire as people thought and the vaccine had a high rate of side effects.

    • In 2009, the H1N1 A vaccine component was a mismatch against the prevailing H1N1 strain. This was recognized in May of 2009, while the seasonal flu vaccine was already being made. It was too late to change course. On June 11, 2009, the WHO declared the H1N1 an epidemic. The WHO, CDC and other experts concurred that a 2nd vaccine covering the H1N1/09 pandemic strain should be created and administered in a second round of vaccinations with deliveries staggered through the end of the year. Almost $8 billion was allocated.  Unfortunately, by October 17, 2009, H1N1 had already infected between 14 – 34 million Americans well before the supplemental flu vaccine was available. IT WAS TOO LATE.

  4. The US and Canada cannot afford another poor-performing seasonal influenza vaccine. We should just assume that one of the A or B strains will not be a good match against the vaccine. If we mass produce a 2nd (or supplemental) flu vaccine, the assumption is that it will be another egg-based version and require at least 5 months lead time to produce. Timeline and production capacity is already tight.

OPTIONS for producing a supplemental influenza vaccine (dose #2) include:
  1. Egg-based vaccine
  2. Recombinant vaccine
  3. Cell-based vaccine

What are the strains included in the 2020-2021 influenza vaccine?
It is recommended that quadrivalent vaccines for use in the 2020 - 2021 northern hemisphere influenza season contain the following:

Egg-Based Vaccines
  • an A/Guangdong-Maonan/SWL1536/2019 (H1N1)pdm09-like virus (a change from the 2019-20 vaccine)
  • an A/Hong Kong/2671/2019 (H3N2)-like virus (a change from the 2019-20 vaccine)
  • a B/Washington/02/2019 (B/Victoria lineage)-like virus (same as the 2019-2020 vaccine)
  • a B/Phuket/3073/2013 (B/Yamagata lineage)-like virus. (same as the 2019-2020 vaccine)

Cell or Recombinant-Based Vaccines
  • an A/Hawaii/70/2019 (H1N1)pdm09 (note – this change from the 2019-20 version is different from the egg-based version)
  • an A/Hong Kong/45/2019 (H3N2) (a change from the 2019-20 vaccine)
  • a B/Washington/02/2019 (B/Victoria lineage) (same as the 2019-2020 vaccine)
  • a B/Phuket/3073/2013 (B/Yamagata lineage) (same as the 2019-2020 vaccine)

The graph below shows the actual flu lineage that the CDC collects. In the 2019-2020 season:
  • Type A (H1N1) was the prevailing strain.
  • Type B (Victoria lineage) was the 2nd most common. The CDC reported that this vaccine strain was only 58% effective.
  • It appears that the strains predicted (and included in the vaccines) were correct, although the circulating virus was somewhat genetically different.
  • If more people were vaccinated, the number of positive tests would be a lot lower.

  • Graph is from the CDC.

Historically, flu season kicks off in October (with the exception of 2009, when it started in Aug/Sept and dropped by end of December).

Graph is from the CDC.

Note that about 3/4 of the 174 million doses that were produced for the 2019-2020 season were quadrivalent (they had the 4 strains identified above; the trivalent removed from the “B/Phuket strain). The CDC acknowledges that all influenza virus vaccines undergo changes when they are grown in eggs. The A (H3N2) virus, in particular, has been shown to result in antigenic changes or “egg-adapted changes”, which reduces the effectiveness.

On March 20, 2020, the European Union recommended the 2020-2021 influenza vaccine strains mimic the CDC’s. Although authorized manufacturers are allowed to submit applications to change the composition, this must happen prior to June 15, 2020. In general, it takes 5-6 months for the first supplies of vaccine to become available once a new pandemic strain of influenza is identified and isolated.

Tweak or swap out a strain.
Historically, the WHO organizes a consultation of the WHO Collaborating Centers twice a year: February for the northern hemisphere vaccine selection and September for the southern hemisphere vaccine selection. We suggest it is time to modify the timeline and reconvene NOW (early May) for determining the strains that have had antigenic shift and identify candidate(s) for a supplemental vaccine that would be administered in the 4th quarter of 2020.

Just because the WHO/CDC have “always done it this way”, should not imply that they continue to do it this way. The system is broken; to only meet once a year (per hemisphere) has not been successful for some time.  If egg-based vaccines are the predominant influenza vaccine, just assume that efficacy will drop in one of the strains. By now (May 4, 2020), scientists at the WHO and CDC should have solid data on which is the weak link.

Good ideas don’t always go away; sometimes it is about the timing. Now is the time.

Kevin Fitzpatrick, Fitzpatrick Translational Science

Our Previous influenza-related publications:
  • 07.23.2019: Could 2019-20 be the Last Season with a Poor Efficacy Flu Vaccine? 
  • 10.17.2018: Uh Oh…. Predicting the Efficacy of the 2018-19 Flu Vaccine 
  • 1.09.2018: Flu Vaccine Match: Is it the Chicken or the Egg? 
  • 10.02.2017: FLU UPDATE – Southern Hemisphere Flu Coming Soon 
  • 2.28.2017: Another Bad Year for Flu Vaccine Strain Prediction 
  • 11.15.2015: Flu Vaccine’s Declining Efficacy – the Past 21 Years 
  • 10.20.2015: Can we predict another failed flu vaccine? (2015-2016)

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