Potential plant adventitious agents: Lessons from animal and insect derived vaccines

1. Potential plant adventitious agents: Lessons from animal and insect derived vaccines P.Minor NIBSC

2. Animal cells • Humans (MRC5,WI38, others) • Monkeys (primary kidney) • Chickens (chick embryo fibroblasts) • Mice/rodents (hybridomas, CHO, Primary hamster kidney)

3. Viruses of concern: Human cells • HIV, Hepatitis B, Hepatitis C • Other viruses more likely to be present (e.g. enteric viruses, CMV, human polyoma viruses in foreskin fibroblasts) • Agents of TSE • Viruses introduced in production In practice human viruses have not been a major issue in vaccine production except for the occasional breakdown in GMP.

4. Viruses of concern: Monkey cells • Definite bad viruses: Herpes B, Marburg, SIV • Possible bad viruses: SV40, SCMV • Others: Foamy virus, other herpes viruses, other simian viruses • The viruses may be lethal, possibly dangerous, or affect production

5. Viruses of concern: chicken eggs • Retroviruses : ALV in yellow fever vaccines • Other agents excluded from specified pathogen free flocks. It is not proven that avian viruses are dangerous in themselves. Some vaccines ( e.g. influenza) are not made on spf eggs.

6. Viruses of concern: rodent cells • Viruses present are not so well known, and the range is based on viruses known to infect mice, as developed for considerations of monoclonal antibody production. • Viruses which may be present in vaccine grown on primary Syrian Hamster Kidney cells are not well known • All are likely to have retroviruses Many serious human viral diseases are transmitted by rodents, including viruses which cause little disease in the normal host.

7. Summary: animal cells • Viruses can be extremely dangerous; if they are present it is unwise to believe that they do not matter even if they have not been shown to be hazardous. • The presence of viruses will hamper production • It is possible to breed virus free animals provided the viruses which may be present are known. This is not always the case.

8. Insect cells • No licensed products yet. • Several clinical trials, one product close to use. • Issues include lack of the appropriate expertise on insect viruses except as means of control of pests. • Most cells have viruses in them and infection can be hard to spot and chronic.

9. Insect viruses • Arboviruses (e.g. flavi, bunya, toga viruses) • Other identified viruses: Asco, Granulo, Baculo, Tetra, Noda, Entomopox etc. • Other non identified viruses: ‘picorna-like’ viruses; rhabdo viruses

10. Insect viruses: implications for humans • Arboviruses cause human disease • Baculoviruses have been reported to infect human cells in vitro to some extent. • There is an evolutionary argument linking some mammalian viruses and insect equivalents Conclusions: Most may not infect humans. They are likely to affect production and yields. It would be better if they were not present. There is uncertainty on the science. There is no entirely appropriate regulatory document.

11. Plant viruses • Position is a little clearer than for insect viruses as plant viruses are economically important. • There is no evidence that plant viruses used in the laboratory have ever infected anyone. • They will affect production. • Viruses could be introduced from other sources (e.g. mice walking over the production area)