Vaccine research and development is lengthy and risky and it requires 10 to 15 years from discovery to license. Approximately one out of ten vaccines that enter clinical development can reach the market. The increasing R&D programs for influenza vaccine development is significantly influencing the growth of the pipeline molecule count in the influenza market.
Universal influenza vaccine initiative (UIVI) is a program conducted to combat the challenges in developing a vaccine that broadly protects against all types of influenza viruses. It encompasses both live attenuated as well as recombinant influenza vaccines for the prevention of influenza. Furthermore, the number of clinical trials for developing a vaccine for treating influenza is steadily increasing. The launch of all molecules in phase III can generate significant revenue on completion of the clinical trials. To educate individuals regarding the influenza virus and also the importance of influenza vaccination, Centre for disease control and Prevention (CDC) conducts national vaccination week. WHO has developed generic campaign materials to support the campaign. Such initiatives can facilitate individuals to gain more knowledge about the preventive measures available against influenza, in turn, driving the demand for these vaccines.
The Advisory Committee on Immunization Practices (ACIP) recommends annual influenza vaccination for everyone, 6 months and older for 2018-2019 flu season. Any licensed age-appropriate flu vaccine including inactivated influenza vaccine (IIV), recombinant influenza vaccine (RIV4) or live attenuated influenza vaccine (LAIV4) with no preference expressed for anyone vaccine over another can be used for vaccination. The IIV, RIV4 or LAIV4 vaccines are to be utilized for quadrivalent and trivalent flu vaccine. The quadrivalent flu vaccine is designed to protect against four different flu viruses; two influenza A viruses and two influenza B viruses. On the other hand, trivalent vaccines include an influenza A (H1N1) virus, an influenza A (H3N2) virus and one influenza B virus. There are two different lineages of B viruses that both circulate during most seasons. However, for trivalent vaccine experts had to choose one B virus. Hence, the vaccine may not equally protect against the group of B viruses not included in the vaccine. Therefore quadrivalent vaccines, aim to give broader protection against circulating flu viruses by adding another B virus to it.
In the United States during 2018-2019, an estimate of 114 – 124 million vaccines out of 163-168 million, will be quadrivalent flu vaccine. 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 candidate vaccine virus. Cell-based flu vaccine production does not require chicken eggs because the vaccine viruses used to make vaccine are grown in animal cells. The recombinant production technology for flu vaccines was 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 at all in the production process. Instead, manufacturers isolate a certain gene (the hemagglutinin or “HA” gene) from a naturally occurring (“wild-type”) recommended vaccine virus. Flublok Quadrivalent is a quadrivalent recombinant influenza vaccine. 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”).
For the vaccine production in 2019, WHO recommended that egg-based quadrivalent vaccines for use in the southern hemisphere influenza season contain the following:
– an A/Michigan/45/2015 (H1N1)pdm09-like virus;
– an A/Switzerland/8060/2017 (H3N2)-like virus;
– a B/Colorado/06/2017-like virus (B/Victoria/2/87 lineage); and
– a B/Phuket/3073/2013-like virus (B/Yamagata/16/88 lineage).
It is recommended that egg-based trivalent vaccines for use in the 2019 southern hemisphere influenza season contain the following:
– an A/Michigan/45/2015 (H1N1)pdm09-like virus;
– an A/Switzerland/8060/2017 (H3N2)-like virus; and
– a B/Colorado/06/2017-like virus (B/Victoria/2/87 lineage).
It is also recommended that the A(H3N2) component of non-egg based vaccines for use in the 2019 southern hemisphere influenza season be an A/Singapore/INFIMH-16-0019/2016-like virus together with the other vaccine components as indicated above. The Key vendors involved in vaccine development are AstraZeneca, CSL, GlaxoSmithKline, Sanofi.
The WHO Collaborating Center for Surveillance, Epidemiology, and Control of Influenza at CDC tested 807 influenza virus specimens collected in the United States for 5months from October 2016 to February 2017. Influenza virus specimens were 94 influenza A (H1N1)pdm09, 519 influenza A (H3N2), and 194 influenza B viruses. These were tested for resistance to the new genera influenza neuraminidase inhibitor antiviral medications oseltamivir, zanamivir, and peramivir. These drugs are currently approved for use against seasonal influenza. All the three antiviral medications could successfully kill influenza viruses.
WHO’s Global Influenza Surveillance Network writes the annual vaccine recipe for influenza vaccine. The constant genetic changes in influenza viruses makes the adjustment of the annual composition of vaccines indispensable. It is imperative to include the most recent circulating influenza A(H3N2), A(H1N1) and influenza B viruses. The network, a partnership of 112 National Influenza Centres in 83 countries, is responsible for monitoring the influenza viruses circulating in humans and rapidly identifying new strains. WHO recommends annually a vaccine that targets the 3 most virulent strains in circulation, based on information collected by the Network.
Along with new viruses introduction to existing vaccines, new molecules are being targeted in the world of flu pharmacotherapy:-
- In the USA, plant biotechnology companies are developing strategies for the large-scale manufacture of influenza vaccines, resulting in a successful Phase I clinical trial;
- In Europe the Pharma-Planta academic consortium gained regulatory approvalfor a plant-derived monoclonal antibody and completed a first-in-human phase I clinical trial;
- The Dutch pharmaceutical company Synthon acquired the assets of Biolex Therapeutics, an established Molecular Pharming company with several clinical candidates produced in their proprietary LEX system based on aquatic plants; and
- The Israeli biotechnology company Protalix Biotherapeutics won FDAapproval for the commercial release of a recombinant form of the enzyme glucocerebrosidase produced in carrot cells, the first plant biotechnology-derived biopharmaceutical in the world approved for the market.
An interesting feature of the four stories outlined above is that they span the use of very different platform technologies addressing different types of molecules which aim to satisfy distinct market demands. Commercial momentum is gathering pace with additional candidates now undergoing or awaiting approval for phase III clinical trials.