October 2020, ScientificAmerican.com 39KAREN BLEIERGetty ImagesAIDS MEMORIAL
QUILT, made up
of 48,000 panels,
commemorates
those who have
died of AIDS-
related causes.sion on the HIV Epidemic. “That is not to say it is
impossible to make such a vaccine, only that we are not
certain of success.” More than 30 years later there still
is no effective vaccine to prevent HIV infection.
From what we have seen of SARS-CoV-2, it interacts
with our immune system in complex ways, resembling
polio in some of its behavior and HIV in others. We know
from nearly 60 years of observing coronaviruses that a
body’s immune system can clear them. That seems to be
generally the case for SARS-CoV-2 as well. But the cold-
causing coronaviruses, just like HIV, also have their
tricks. Infection from one of them never seems to confer
immunity to reinfection or symptoms by the same strain
of virus—that is why the same cold viruses return each
season. These coronaviruses are not a hit-and-run virus
like polio or a catch-it-and-keep-it virus like HIV. I call
them “get it and forget it” viruses—once cleared, your
body tends to forget it ever fought this foe. Early stud-
ies with SARS-CoV-2 suggest it might behave much like
its cousins, raising transient immune protection.
The path to a SARS-CoV-2 vaccine may be filled with
obstacles. Whereas some people with COVID-19 make
neutralizing antibodies that can clear the virus, not
everybody does. Whether a vaccine will stimulate such
antibodies in everyone is still unknown. Moreover, we
do not know how long those antibodies can protect
someone from infection. It may be two or three years
before we will have the data to tell us and any confi-
dence in the outcome.
Another challenge is how this virus enters the body:
through the nasal mucosal membranes. No COVID-19
vaccine currently in development has shown an ability to
prevent infection through the nose. In nonhuman
primates, some vaccines can prevent the disease from
spreading efficiently to the lungs. But those studies do
not tell us much about how the same drug will work in
humans; the disease in our species is very different from
what it is in monkeys, which do not become noticeably ill.
We learned with HIV that attempts to prevent virus
entry altogether do not work well—not for HIV and not
for many other viruses, including influenza and even
polio. Vaccines act more like fire alarms: rather than
preventing fires from breaking out, they call the
immune system for help once a fire has ignited.
The hopes of the world rest on a COVID-19 vaccine. It
seems likely that scientists will announce a “success”
sometime this year, but success is not as simple as it
sounds. As I write, officials in Russia have reported
approving a COVID-19 vaccine. Will it work? Will it be
safe? Will it be long lasting? No one will be able to provide
convincing answers to these questions for any forthcom-
ing vaccine soon, perhaps not for at least several years.
We have made remarkable improvements in our
molecular biology tools since the 1980s, yet the slow-
est part of drug development remains human testing.
That said, the infrastructure created for HIV/AIDS
research is accelerating the testing process now. Thir-
ty thousand volunteers around the world participate
in networks built by the National Institutes of Healthfor studies of new HIV vaccine candidates, and these
networks are being tapped for initial testing of
COVID-19 vaccines, too.
When doctors treat a patient who is likely to die, they
are willing to risk that a drug might sicken the patient
but still save their life. But doctors are less willing to do
that to prevent disease; the chances of causing greater
harm to the patient are too high. This is why for decades
the quest for a vaccine to prevent HIV infection has lagged
so far behind development of therapeutic drugs for HIV.FOCUS ON TREATMENTS
thEsE drugs now stand as an incredible success story.
The first set of HIV drugs were nucleic acid inhibi-
tors, known as chain terminator drugs. They inserted
an additional “chain terminating” nucleotide as the
virus copied its viral RNA into DNA, preventing the HIV
chain of DNA from elongating.
By the 1990s we had gotten better at using combina-
tions of drugs to control HIV infections soon after
patients were exposed. The first drug, AZT, found imme-
diate application for health care workers who acciden-
tally had a needlestick injury that infected them with
contaminated blood. It was also used to reduce mother-
to-child transmission. For example, prenatal treatments
for mothers with AIDS at that time reduced the number
of babies born infected by as much as two thirds. Today
combination chemotherapy reduces mother-to-child
transmission to undetectable levels.
The next set of drugs was protease inhibitors, one of
which I helped to develop. The first was introduced in
1995 and was combined with other drugs in treating
patients. These drugs inhibited the viral protease
enzyme responsible for longer precursor proteins in the
short active components of the virus. But there is a
fundamental problem with these drugs, as well as those
that inhibit viral polymerases, which help to create
virus DNA. Our bodies also use proteases for normal
functioning, and we need polymerases to replicate our
own nucleic acids. The same drugs that inhibit the viral© 2020 Scientific American © 2020 Scientific American