When the H1N1 swine flu appeared in the spring of 2009, a candidate vaccine virus (CVV) was quickly produced, and within 6 months the first human vaccines began to ship. It was a remarkable feat – one where success was far from guaranteed – but one made easier as the 2009 H1N1 virus was essentially a `strain change’ from the seasonal vaccine.
Producing a vaccine against an avian flu virus is a far more complex process, both legally and logistically.
Experimental H5 and H7 avian flu vaccines have proved poorly immunogenic in the past – requiring unusually large amounts of antigen (up to 12x normal), spread across two shots several weeks apart - to induce a good immune response. They also often fail to grow well in eggs, further complicating the manufacturing process.
Two years ago the NIH announced the start of a year-long Phase II Clinical Trials On H7N9 Vaccine Candidates, and as we saw with earlier H5N1 vaccines, it was announced this summer that an unadjuvanted vaccine produced extremely poor results (see JAMA: Immune Response Of H7N9 Vaccine With & Without Adjuvant).
With a growing roster of HPAI H5 viruses (H5N1, H5N8, H5N2, H5N6) spreading globally - and continuing to mix and potentially reassort with other avian viruses - there is understandable concern that one of these viruses could someday pose a pandemic threat.
Last March the World Health Organization’s Weekly Epidemiological Record (WER) published a new review of currently circulating zoonotic influenza viruses, and their recommendations included the development of two new vaccine virus candidates.
Both candidates were H5’s; one based on the recent changes observed in Egypt’s H5N1 virus, and the other based on the recent introduction of H5N8 into North America.
Without discussing the status of any current vaccine projects in the works, today the CDC has published an extremely informative primer on the steps it takes to produce an Candidate Vaccine Virus for an HPAI avian flu. I’ve only excepted the opening, so follow the link below to read it in its entirety, after which I’ll be back with a postscript.
On this Page
- Production of the candidate vaccine virus (CVV)
- Quality Assessment
- Determination of Attenuation
- Request for CVV Exclusion from the USDA Select Agents List
- Distribution to Vaccine Manufacturers and Other Stakeholders
A candidate vaccine virus (CVV) is an influenza (flu) virus that has been prepared by CDC or another public health partner that can be used by vaccine manufacturers to produce a flu vaccine. In addition to preparing CVVs for seasonal flu vaccine production, CDC routinely develops CVVs for novel avian influenza (bird flu) viruses with pandemic potential as part of pandemic preparedness activities. Some novel bird flu viruses with pandemic potential are "highly pathogenic avian influenza" (HPAI) viruses, which means they are deadly to domestic poultry, including chickens. Data collected through global and animal flu surveillance informs the selection of CVVs, and experts choose CVVs against bird flu viruses in nature ("wild type" viruses) that pose a risk to human health.
The creation of a CVV for a novel bird flu virus is a multistep process that takes on average around two months from start to finish. Creating a bird flu CVV is usually more complicated than the process for creating a seasonal flu CVV. There are five steps involved in the creation of a bird flu CVV, including the following:
- Production of the candidate vaccine virus (CVV) ;
- Quality assurance;
- Determination of attenuation;
- Request for USDA Select Agent exclusion; and
- Distribution of the CVV to vaccine manufacturers and other stakeholders.
These steps are described below.
Having a proven Candidate Vaccine Virus already tested and approved can save months of valuable time if mass production and distribution of a vaccine is ever required. But even with all of that work already done, one shouldn’t expect to be rolling up their sleeve anytime in the opening months of novel flu pandemic.
Add in the probable need for two shots (4 weeks apart), and the logistics of production and delivery are effectively doubled.
While having a viable vaccine is an important part of the pandemic preparedness toolkit, in the opening months of any global outbreak we’ll be depending on primarily on Nonpharmaceutical Interventions (NPIs) like social distancing, school closures, hand hygiene & masks along with neuraminidase (NA) inhibiting antiviral drugs (NAIs) like oseltamivir (Tamiflu ®) and Zanamivir (Relenza ®) to help mitigate its impact.