Self-spreading vaccines for release into the environment near-future application: in process of transferring the technology to manufacturer for scale-up.
Hello…
Thanks to everyone for a stimulation discussion so far.
My name is Dr. Guy Reeves, from the Max Planck Institute for Evolutionary biology (Germany), I am an evolutionary genenetitst with interests in viral techniques intended for environmental modification. I am an inventor on a granted patent related to gene drive (EP2934093B1).
This post to a significant extent echos parts of Dr Eva Sirinathsinghji above.
In that past three years it has been reported by a commercial company that they have developed two self-spreading vaccines. One for Lassa fever virus in West African rat species and another for Ebola virus in primates.
—Time frame—
The Lassa fever virus vaccine for release into wild rat populations is reported by the CEO to potential investors (January 2023)
“ We are in the process transferring the technology to a West-African manufacturer … so that particular tech-transfer can be scaled up and then there is a possibility then obviously having somebody who can manufacture at scale to make that vaccine available in the region”.
see time point 6:10 (but see also explanatory section starting at 2:38)
https://www.youtube.com/watch?v=KHFjabspTcMor see also
https://thevaccinegroup.com/tvg-successfully-completes-darpa-funded-transmissible-lassa-fever-vaccine-project/https://static1.squarespace.com/static/5d927ef93f54836cb17542c1/t/5e74072e6f3a42255b9573fe/1584662333204/BIG+WIN-New+Countermeasures.pdfhttps://thevaccinegroup.com/science/ note vaccine development platform that is “Evolved to spread easily through host population.”
Simply put, self-spreading vaccines are live laboratory modified viruses that are developed to spread between vertebrate hosts when released into the environment. Furthermore, that they rely on this property to (in theory) autonomously achieve population wide immunisation of wild populations and potentially also subsequent generations.
Self-spreading vaccines are always live viral vaccines that are genetically modified (i.e. LMOs). Where reported, development has occurred in biosafety level 3 or 4 facilities (Bárcena et al., 2000; Tsuda et al., 2011), though they are intended for release into the environment to spread with epidemic like properties.
Self-spreading viral techniques for use in the environment are not technically new, but until now there has been a well established norm among virologists that their use or development is highly problematic relative to existing available alternatives (Lentzos 2022).
—To date no self-spreading vaccine has been licensed (for either medical or veterinary use), despite claims otherwise by proponents of self-spreading viral approaches —.
The only ambiguous case is 2019 USA approval of the experimental release of the self-spreading Live Raccoon Poxvirus Vector (RCN-CAL/SP) in bats as an conservation measure, where it was stated that
“Because the issues raised by field testing and by issuance of a license are identical, APHIS has concluded that the EA that is generated for field testing would also be applicable to the proposed licensing action. Provided that the field test data support the conclusions of the original EA and the issuance of a FONSI, APHIS does not intend to issue a separate EA and FONSI to support the issuance of the product license, and would determine that an environmental impact statement need not be prepared. APHIS intends to issue a veterinary biological product license for this vaccine following completion of the field test provided no adverse impacts on the human environment are identified and provided the product meets all other requirements for licensing.”
https://www.regulations.gov/document/APHIS-2019-0043-0001This statement by APHIS and the timeframe mentioned in statements by the CEO reproduced at the start of this posting raise the question of wether self-spreading viral approaches can be planing to follow the highly regulated and internationally notified testing and licensing process that vaccines follow (including the high successful oral bait vaccines for rabies which are not self-spreading).
—Relevance to CBD —
To date, proposed modified self-spreading viral approaches for use in wildlife can usefully be placed in one of two types (Lentzos 2022):
1 Experimental approaches to kill or sterilize mammalian wildlife or pests as a means to reduce their population sizes, also called wildlife management.
2 Experimental approaches to vaccinate mammalian wildlife to protect them from disease or to limit their capacity to act as reservoirs for vectored diseases.
The topic of this posting is class 2
Regulators have for decades repeatedly noted the potentially profound consequences of such viral techniques for use in biodiversity, older but thoughtful examples include (CBD 2007 or WHO 1993) . The obvious issues raised remain unresolved with no obvious current effort to address them, despite ongoing development efforts.
Given the inherent difficulty in field testing a technology that is to a significant extent designed to “get away” and the absence of any international notification for cross-border export of self-spreading vaccines or experimental releases of veterinary self-spreading vaccines. It appears the case that as the broader vaccine community focuses on moving away from higher risk approaches where effective alternatives can be developed (e.g. replacing live attenuated vaccines generated by selection), there is a considerable potential for the whole world to be surprised by a very small group of funders and mostly evolutionary biologists moving rapidly in the direction of increasing the risk profile of vaccines.
This meeting is occurring during the duration of this forum and provides some insight into the current interest in these techniques.
https://transmissiblevaccines.org/workshop-dev-vaccines/1.
Bárcena, J., M. Morales, B. Vázquez, J. A. Boga, F. Parra, J. Lucientes, A. Pagès-Manté, J. M. Sánchez-Vizcaíno, R. Blasco, and J. M. Torres. 2000. Horizontal Transmissible Protection against Myxomatosis and Rabbit Hemorrhagic Disease by Using a Recombinant Myxoma Virus. J Virol. 74:1114–1123. Available from:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC111445/CBD 2007. ‘Report of the Canada-Norway Expert Workshop on Risk Assessment for Emerging Applications of Living Modified Organisms UNEP/CBD/BS/COP-MOP/4/INF/13’, 39.
https://www.cbd.int/kb/record/meetingDocument/58217?RecordType=meetingDocument&Event=BSRARM-01.
F. Lentzos, E. P. Rybicki, M. Engelhard, P. Paterson, W. A. Sandholtz, R. G. Reeves, Eroding norms over release of self-spreading viruses. Science. 375, 31–33 (2022). Available from:
http://web.evolbio.mpg.de/HEVIMAs/WHO 1993 Informal Consultation on Reproductive Control of Carnivores, Geneva, 16 June 1993 :. 1993.
https://apps.who.int/iris/handle/10665/60995.
Tsuda, Y., P. Caposio, C. J. Parkins, S. Botto, I. Messaoudi, L. Cicin-Sain, H. Feldmann, and M. A. Jarvis. 2011. A Replicating Cytomegalovirus-Based Vaccine Encoding a Single Ebola Virus Nucleoprotein CTL Epitope Confers Protection against Ebola Virus. T. W. Geisbert, editor. PLoS Negl Trop Dis. 5:e1275.
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Note that self-spreading vaccines are also described as: transmissible, contagious, horizontally-transferable, self-disseminating and founder-based vaccines. Recently a hypothetical term “transferable vaccine” has also be introduced to denote live self-spreading vaccines where transmission only occurs to individuals in direct contact with the originally inoculated individuals (Nuismer and Bull, 2020; Technology Networks, 2022). However, we are unaware of any evidence that such a class of viruses exists--particularly as viral transmissibility is always a dynamic parameter in complex environmental situations--. A precise definition of sefl-spreading vaccines can be found in box 1 of (Lentzos 20022).
Currently, there are 4 proposals for self-spreading vaccines, only one of which has resulted in recent approved releases.
1 Vaccinate African primates to inhibit their infection by the Ebola virus with the aim to limit their capacity to act as a wildlife reservoir for transmission to humans (PREEMPT, 2018; TVG, 2021; PREEMPT, 2022).
2 Vaccinate a number of rat species in West Africa to inhibit their infection by the Lassa fever virus with the aim to limit their capacity to act as a wildlife reservoir for transmission to humans (PREEMPT, 2018; PREEMPT, 2022; Regulatory News Service, 2022).
3 Vaccinate numerous North American bat species to reduce their susceptibility to an emergent fungal infection for the purposes of bat conservation. This proposal has resulted in the release of a genetically modified raccoon pox virus starting in 2019 (Rocke et al., 2019; USDA-APHIS, 2019).
4 Vaccinate various vampire bat species, that are mostly currently restricted to Central and South America, to inhibit their infection by the Rabies virus with the aim to limit their capacity to act as a wildlife reservoir for transmission to humans, but has primarily a bat conservation motivation, as highly effective human vaccines for rabies could be made available to human communities (Bakker et al., 2019; Streicker et al., 2022).
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