Initial delays shouldn’t affect availability
Despite some initial delays, supplies of flu vaccine for the 2019-2020 season are expected to be more than adequate to meet demand. Its effectiveness, however, will only be measured at the end of the season, as it must be every flu season.
“As of now, it looks like there will be enough flu vaccine available from all manufacturers to meet patient demand,” says Bill Smith, president of Main Street Vaccines, An NDC Company. “The last several seasons, supply has outpaced demand in the marketplace.
“[As of mid-July], Sanofi Pasteur announced a three-to-four-week delay in shipping commitments, with partial shipments beginning in late August or September, and all shipments completed by the end of November. The reason they cited for this delay is that the World Health Organization and the FDA delayed selection of the A/H3N2 strain by one month. Historically, though, even when delivery delays occur, it has not impacted the overall supply to the market.
“It will be important for distributor reps to work with their customers to help them plan their immunizations and clinics when vaccine is available.”
“Manufacturing could not begin until the selection was made by WHO and confirmed by the FDA,” said Michael Szumera, head of Sanofi Pasteur U.S. communications, responding to Repertoire by email in mid-July. (Sanofi manufactures Fluzone Quadrivalent and High-Dose vaccines, as well as Flublok Quadrivalent, a recombinant, protein-based flu vaccine for persons 18 and over.)
“We are still on track to produce approximately 70 million doses of seasonal vaccine to support nationwide immunization campaigns,” he said. “At this time, we anticipate a slight delay of approximately one month in the first shipment of our vaccine, which will be the case across all manufacturers. Shipping of our products will begin in mid-August, with all shipments completed by the end of November.”
As AstraZeneca spokesperson told Repertoire in mid-July that it is likely there may be lower total amounts of vaccine available than the company had anticipated. AstraZeneca makes the FluMist® Quadrivalent intranasal flu vaccine.
“Following the WHO’s recommendations, it takes approximately six to eight months to produce and approve the full global supply of influenza vaccines,” said the spokesperson. “The WHO’s recommendation of A/H1N1 and A/H3N2 strains for inclusion in the 2019-2020 FLUMIST® QUADRIVALENT formulation have yielded lower amounts of potential doses. Lower yields do not impact the quality of the vaccine, but may result in a lower total amount of vaccine available.”
WHO’s recommendation may lead to delayed delivery of all influenza vaccines, the spokesperson added. “To ensure availability of high-quality product as soon as possible, deliveries of FLUMIST QUADRIVALENT will be spread across the flu season, as opposed to being concentrated in the initial months of the season.”
How effective?
The most common way flu vaccines are made is using an egg-based manufacturing process that is more than 70 years old. New methods may prove to be more efficient, including cell-based production and recombinant vaccines.
But effectiveness can vary year to year, based on the flu strains that are circulating, says Smith. “Unfortunately, if the virus mutates during the season, as we have seen happen in the past, this can decrease overall effectiveness of the flu shot.”
The past season’s flu vaccine, for example, was only about 30% effective overall, and ineffective against a late-surging strain, reports the CDC. Even so, CDC says that last season’s flu vaccine provided protection against a substantial number of illnesses, hospitalizations and deaths, says Szumera of Sanofi Pasteur.
“Flu viruses are constantly changing, and vaccine effectiveness is often impacted by naturally occurring strain drift,” he says. “However, many studies have found that even in seasons when flu vaccines provide lower protection against infection, they still provide substantial reductions in outcomes such as hospitalizations and death. CDC and other health officials continue to encourage people to get a flu shot every year.”
Meet the 2019-2020 flu vaccine
The composition of U.S. flu vaccines is reviewed annually and updated as needed to match circulating flu viruses, according to the Centers for Disease Control and Prevention. Flu vaccines protect against the three or four viruses (depending on the vaccine) that research suggests will be most common. For 2019-2020, trivalent (three-component) vaccines are recommended to contain:
- A/Brisbane/02/2018 (H1N1)pdm09-like virus (updated).
- A/Kansas/14/2017 (H3N2)-like virus (updated).
- B/Colorado/06/2017-like (Victoria lineage) virus.
Quadrivalent (four-component) vaccines, which protect against a second lineage of B viruses, are recommended to contain the three recommended viruses above, plus B/Phuket/3073/2013-like (Yamagata lineage) virus.
The World Health Organization (WHO) made the selection of the H1N1 and both B components for 2019-2020 Northern Hemisphere flu vaccines on February 21, and at that time decided to delay the decision on an H3N2 vaccine component. FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) also selected the H1N1 and B components at their first meeting on March 6, but also decided to postpone the selection of the H3N2 component. WHO selected the H3N2 component listed above on March 21, 2019. VRBPAC chose the same H3N2 component for U.S. vaccines on March 22, 2019.
A vote of confidence for nasal spray this flu season
The American Academy of Pediatrics this spring advised families to vaccinate their children against influenza this season with either the flu shot or the nasal spray vaccine for the best protection against the virus during the 2019-2020 flu season.
The recommendation differs slightly from last year, when AAP cited a preference for the injected vaccine over the nasal spray – except in cases where a child refused the shot – based on questions about the effectiveness of the nasal spray in previous seasons.
The AAP Board of Directors approved both options after reviewing the latest data on the inactivated vaccine (IIV), which is injected, and the quadrivalent live attenuated influenza vaccine (LAIV4), which is a nasal spray given to healthy patients ages 2 through 49.
AAP did not recommend the nasal spray during the 2016-17 and 2017-18 flu season since the spray did not work as well against influenza A/H1N1 strain during the 2013-2014 and 2015-2016 flu seasons. In 2017 the manufacturer of the nasal spray made changes to the formulation to include a new A/H1N1 strain, and this year infectious disease experts are encouraged by new data from Great Britain that – while dependent on a limited number of cases in other countries – supports the spray’s effectiveness against some strains of influenza.
What’s in a flu vaccine?
Three different influenza vaccine production technologies are approved by the U.S. Food and Drug Administration:
- Egg-based flu vaccine. The most common way that flu vaccines are made is using an egg-based manufacturing process, which has been used for more than 70 years. Egg-based vaccine manufacturing is used to make both inactivated (killed) vaccine (usually called the “flu shot”) and live attenuated (weakened) vaccine (usually called the “nasal spray flu vaccine”).
- Cell-based flu vaccine. In 2012 the FDA approved a cell-based production process for flu vaccines. At one time, this production process also began with egg-grown Candidate Vaccine Viruses (CVVs), per FDA regulations. However, on August 31, 2016, FDA issued an approval for Seqirus, the sole FDA-approved cell-based flu vaccine manufacturer in the United States, to use cell-grown CVVs. Cell-based flu vaccine production does not require chicken eggs because the vaccine viruses used to make vaccine are grown in animal cells. Cell culture technology has the potential for a faster start-up of the flu vaccine manufacturing process.
- Recombinant flu vaccine. Approved for use in the U.S. market in 2013, this production method does not require an egg-grown vaccine virus and does not use chicken eggs in the production process. Instead, manufacturers isolate a certain gene (the hemagglutinin or “HA” gene) from a naturally occurring (“wild type”) recommended vaccine virus. This HA gene is then combined with portions of another virus that grows well in insect cells. This “recombinant” vaccine virus is then mixed with insect cells and allowed to replicate in these cells. The flu HA protein is then harvested from these cells and purified.
Source: Centers for Disease Control and Prevention
A universal vaccine?
Here’s an idea: A “universal” influenza vaccine that can provide long-lasting protection for all age groups from multiple influenza subtypes.
Right now, it’s a dream, admit scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. But the first clinical trial of a universal influenza vaccine candidate is examining the vaccine’s safety and tolerability as well as its ability to induce an immune response in healthy volunteers.
The experimental vaccine – known as H1ssF_3928 – is designed to teach the body to make protective immune responses against diverse influenza subtypes by focusing the immune system on a portion of the virus that varies relatively little from strain to strain. The vaccine candidate was developed as part of a broader research agenda to create a so-called “universal” influenza vaccine that can provide long-lasting protection for all age groups from multiple influenza subtypes, including those that might cause a pandemic.
The clinical trial is being conducted at the NIH Clinical Center in Bethesda, Maryland. It is being led by Grace Chen, M.D., of NIAID’s Vaccine Research Center (VRC) Clinical Trials Program.
The VRC expects the clinical trial to complete enrollment by the end of 2019 and hopes to begin reporting results in early 2020. For more information about the trial, visit ClinicalTrials.gov and search identifier NCT03814720.