science.org SCIENCEviromes, which are speculated to play a de-
fining role in many spillover events, makes
it extraordinarily difficult to mitigate spill-
over risk using wildlife vaccines. Although
a massive increase in viral monitoring in
wildlife might in some theoretical circum-
stances provide a time-limited degree of
insight upon which to base preemptive
vaccine design, it could only have a very
indirect impact on prioritizing what ge-
netic event, in which wildlife species, and
at what location might present a substan-
tive risk for the emergence of a new virus.
In addition, the extraordinary practical
complexity of wildlife vaccination, particu-
larly in terms of sustaining and monitoring
the immune response in wildlife popula-
tions, has not been explicitly addressed by
funders or scientists promoting self-spread-
ing vaccines ( 13 ). The combination of these
concerns in the context of emerging new
viral pathogens has led most virologists to
consistently advocate for surveillance at the
human–animal interface particularly in re-
gions of ecological disturbance, rather than
the riskier mass prospective development of
self-spreading vaccines ( 8 ).
A more extreme application touted is the
use of self-spreading viruses in human vac-
cination ( 8 ). This is often paired with an
acknowledgment that use in humans would
likely come with insurmountable ethical and
safety concerns, as well as public outcry ( 1 , 2 ).
From a security perspective, it is important
to note that, with the exception of height-
ened safety standards, it is broadly true that
whatever self-spreading vaccines could be
developed for wildlife could be more easily
generated, from a technical perspective, for
humans. This is because monitoring popula-
tions for levels of immunity and viral evolu-
tion is much easier in humans than in wild-
life, and critically, the hurdles outlined above
would not apply in quite the same way, as
by definition, the target virus will be well
known to science.
Theoretical claims of suppressed viral
evolution and their assumed predetermined
lifetimes in the environment currently re-
main peripheral within the scientific com-
munity. However, this seems paradoxical if
the accumulating collection of more than 15
publications over the past 5 years does in-
deed outline a genuinely innovative path to
safely achieving and maintaining high levels
of immunity, using a fraction of the resources
and time that conventional vaccination pro-
grams require. Why would recognition of this
(re)emerging field be so low, if there is even
a remote possibility of the promoted thor-
oughly transformational goals being realized?
One reason might be that experts from
across relevant disciplines will view claims
of suppressing viral evolution, or sustainably
fine-tuning transmissibility in complex, dy-
namic environments, with a high degree of
informed skepticism. Alternatively, perhaps
they may see nothing genuinely new in the
claims because it has been technically possi-
ble to generate such vaccines for decades ( 4 ).
Indeed, the pervasive challenge had always
been to minimize or eliminate transmission
of human vaccines based on live viruses
between individuals. This is for reasons of
safety and ethics (e.g., the infection of im-
munocompromised individuals or nursing
infants), but also for practical considerations
(e.g., retaining the capacity to suspend or
geographically restrict trials). It has been
argued that existing live poliovirus vaccines
are “self-spreaders” ( 2 , 11 ). Although they
are not self-spreading vaccines as the term
is used here (see the box), the vaccine-asso-
ciated paralytic poliomyelitis (caused by un-
controlled community transmission of Sabin
type 2 polio vaccine) does present an object
lesson in the risk of transmissibility. An on-
going example of efforts to further minimize
the impact of unwanted transmission is the
early-stage development of a Sabin type 2
polio vaccine strain that aims to limit back-
mutation to virulence ( 14 ).Self-spreading vaccine research contin-
ues to proceed despite a lack of new in-
formation that would compellingly refute
long-standing evidence-based norms in vi-
rology, evolutionary biology, vaccine devel-
opment, international law, public health,
risk assessment, and other disciplines.
Providing such evidence, along with antici-
pated benefits, possible harms and risks,
and appropriate precautionary measures,
should have been considered a critical first
step in undertaking self-spreading vaccine
research. Furthermore, there are currently
no fully, or even partially, articulated pro-
posals for regulatory pathways that could
establish self-spreading vaccines as not
only safe, effective, and useful but also,
crucially, as the patchy uptake of COVID-19
vaccines has shown, publicly trusted.
And if, as claimed, self-spreading vac-
cines do indeed represent a flexible and
transformational technology in areas as
diverse as conservation, human health,
and agriculture, then additional justifica-
tion is needed for why efforts would not be
exclusively focused on addressing pressing
needs in the countries funding or develop-
ing these approaches. This was the case forTo date, proposed modified self-spreading viral approaches can usefully be placed in one of
three types:- Experimental approaches to kill or sterilize mammalian wildlife or pests as a means to
reduce their population sizes, also called wildlife management ( 3 ). - Experimental approaches to vaccinate mammalian wildlife to protect them from disease
( 4 , 15 ) or to limit their capacity to act as reservoirs for vectored diseases ( 1 , 2 ). - Speculations about applications in humans as vaccines ( 1 , 2 , 8 ).
The terms “self-spreading,” “transmissible,” “self-disseminating,” “contagious,” and “hori-
zontally transferable” have all been used interchangeably to describe artificially modi-
fied viruses developed for applied uses that intentionally retain the capacity to transmit
between individual hosts upon their release into the environment. Here we adopt the term
“self-spreading virus,” defined as satisfying both of the following criteria:- Intentionally developed to be transmissible between individual hosts in the environment,
where safety testing, efficacy testing, and regulatory approval incorporate the numerous
consequences arising from this property. - Possessing deployment strategies that fundamentally rely upon transmission between
individual hosts for their successful application (see the figure).
Viral transmissibility between individual hosts is in almost all circumstances dynamic,
particularly in complex environments. For example, coinfection of wild-type and geneti-
cally modified released viruses has the capacity to enhance transmission rates of the latter
through viral complementation. Furthermore, spontaneous recombination has the potential
to alter the transmissibility of parts or all of the released viral genomes. In some recent
publications the vague concept of “transferable vaccines” has been introduced ( 9 ), which
are proposed to be in some respects intermediate between conventional and self-spreading
vaccines. However, it is unclear to us if their hypothecated existence has any basis in fact,
and as such their consideration is potentially unhelpful.
Currently, none of the licensed genetically modified viruses for use in the environment are
transmissible, including the various widely applied oral-bait rabies vaccines for wildlife.What are self-spreading viruses?
INSIGHTS | POLICY FORUM
32 7 JANUARY 2022 • VOL 375 ISSUE 6576