Thread by @stuartjdneil

1. Something I haven’t seen much discussion of at #PathogensProject is about surrogate experimental systems for dangerous pathogens.

2. Predominantly from the retrovirus field, the establishment of lentiviral pseudotype systems (PLVs) for studying enveloped viral glycoproteins, as well as replication competent Rhabdovirus-based systems are cheap, easy and fast.

3. While there are limitations on some of the cell biology they can tell you about the dangerous virus of choice, they can give you most of the info you need to know including receptor, host range tropism, sensitivity to antibodies, vaccine escape etc.

4. Subgenomic replicons of some viruses can be useful, and replication incompetent reverse genetic systems like the one my lab use for Ebola virus also have their place, and make a lot of work possible that is just not tractable at high containment with the live pathogen.

5. But 2 areas I would point to. A general one – journal editors should recognise the value of surrogate systems used properly (as is now generally the case for PLVs), but they need to resist the lazy reviewer trope of ‘show with the real virus’ unless there is a clear need.

6. Secondly, in the UK (and I believe elsewhere in Europe), we are limited in using Rhabdovirus systems like VSV by a clash between the HSE governing human pathogens and DEFRA with animal pathogens. VSV is a problem in livestock, but fairly benign in humans and mice.

7. In the UK we cannot use VSV without some really tortuous SAPO paperwork and justification even in a BSL3 lab, yet the Merck EBOV vaccine is based on it, and in the US it is safely contained within BSL2 labs without raising any issues.

8. This raises a key question of proper, harmonised EVIDENCE BASED worldwide biosafety and biosecurity classifications for all viral pathogens. Of course, Ebola, Nipah, Lassa etc need to be BSL4.

9. Of course, sarbecoviruses should be BSL3. But why should Dengue (a mosquito-borne virus) be BSL2 in many parts of the world where it is endemic..

10. but BSL3 + ACTSA5 biosecurity requiring the lab be bomb proof and linked to armed response antiterrorist police in the UK where we don’t have the mosquitos (yet…).

11. If even this came out of an international body, we would be making progress.