For decades, studies have found hints that some vaccines help protect against
pathogens they weren’t designed to target. Researchers are now striving to
understand how such inoculations might be used to save more lives.BY SHAWNA WILLIAMSVaccines
with a Bonus
A
s a physician-researcher specializ-
ing in infections in newborns, Tobi
Kollmann is laser focused on how to
stop babies from dying. While mortality for
kids under five years old has dropped sub-
stantially in recent decades, he says, there has
been little improvement in the rate of deaths
in the first week of life. Indeed, of the 5.2 mil-
lion children under 5 years old the World
Health Organization estimates died last year
of preventable or treatable causes, nearly
half—2.4 million—died before reaching
four weeks of age, and most newborn deaths
occurred in the first week after birth. Having
spent time in African countries where neo-
natal mortality is common and witnessed the
frustration of colleagues there with their lim-
ited options for preventing it, Kollmann, now
at the Telethon Kids Institute in Perth, Aus-
tralia, says he wanted to find solutions that
could be implemented immediately.
So when Kollmann came across a 2011
study that found giving the tuberculosisvaccine (called bacille Calmette-Guérin,
or BCG) to low-weight infants in Guinea-
Bissau at birth cut their mortality rate
in their first four weeks of life in half—
not because of the protection it offered
against tuberculosis itself, but by reducing
the risk of sepsis and other infections—
it caught his attention.^1 “That to me was
just unimaginable,” he says. Around 2012,
Kollmann attended a meeting of research-
ers studying such off-target effects of vac-
cines and sat in on a talk by one of the
authors of the 2011 study, Dutch anthro-
pologist Peter Aaby, founder of the Ban-
dim Health Project. Aaby spoke about
the history of research on two vaccines
linked to declines in all-cause mortality:
BCG and the measles vaccine, which both
incorporate live, attenuated pathogens.
Kollmann “was just shocked how such a
tool that could potentially be so incredibly
effective... could have been kept under
the wraps for so, so long.”Kollmann didn’t wait long to begin
studying what he terms the pathogen-
agnostic effects of BCG, coauthoring sev-
eral reviews on the topic and, more recently,
studying the mechanisms of the effects
in animals. Other vaccines, such as the
smallpox and live polio vaccines, have also
yielded hints in observational studies that
they could provide some protection, at least
temporarily, from pathogens other than
those they target. In recent years, some
randomized controlled trials have provided
more-solid evidence for such protections.
Despite decades of reports of vaccines’
off-target effects, however, the phenome-
non has received relatively little attention,
and researchers have only a nascent under-
standing of the mechanisms. While critics
argue that some of the claims made about
pathogen-agnostic effects outstrip the avail-
able evidence, Kollmann says he thinks
many experts have been slow to embrace
their potential of pathogen-agnostic11.2020 | THE SCIENTIST 21