Abstract
A major lesson learned from the public health response to the 2009 H1N1 pandemic was the need to shorten the vaccine delivery timeline to achieve the best pandemic mitigation results. A gap analysis of previous pre‐pandemic vaccine development activities identified possible changes in the Select Agent exclusion process that would maintain safety and shorten the timeline to develop candidate vaccine viruses (CVVs) for use in pandemic vaccine manufacture. Here, we review the biosafety characteristics of CVVs developed in the past 15 years to support a shortened preparedness timeline for A(H5) and A(H7) subtype highly pathogenic avian influenza (HPAI) CVVs. Extensive biosafety experimental evidence supported recent changes in the implementation of Select Agent regulations that eliminated the mandatory chicken pathotype testing requirements and expedited distribution of CVVs to shorten pre‐pandemic and pandemic vaccine manufacturing by up to 3 weeks.
Highlights
Pathogenic avian influenza (HPAI) viruses have the poten‐ tial to cause zoonotic infections and to acquire human‐to‐human transmissibility, leading to a pandemic
Inadvertent introduction of reverse genetic (RG) plasmids encoding wild‐type HA from Highly pathogenic avian influenza (HPAI) viruses to plasmid stock to be used in the preparation of candidate vaccine viruses (CVVs) would yield mixed viral populations with potential virulence for chickens and other avian species
A set of tests are per‐ formed after each CVV is produced to identify signals inconsistent with those that define the CVV as similar to low pathogenicity avian influenza (LPAI) viruses (Table 3), often including complete genome coding sequence analysis using a ‐generation sequencing (NGS) approach with verification of the monobasic HA cleavage site and Puerto Rico/8/34 (PR8) internal gene segments; trypsin‐dependent plaque formation in cell monolayers; chicken embryo lethality test; and often an additional exclusivity test for CVV quality control consisting of a real‐time re‐ verse transcription‐polymerase chain reaction assay for H5 and H7 HA genes from HPAI virus lineages that is performed by an independent QA laboratory.[47]
Summary
Pathogenic avian influenza (HPAI) viruses have the poten‐ tial to cause zoonotic infections and to acquire human‐to‐human transmissibility, leading to a pandemic.
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