past few years, she has published papers
on a second-generation algorithm she
designed in collaboration with her husband
called an Epigraph. This is an efficient graph-based algorithm for designing vaccine antigens to optimize potential epitope coverage
(an epitope is a small part of a pathogen
protein that the immune system can see).
Epigraph vaccine antigens are functionally
similar to mosaic vaccines, but in contrast to
the mosaic algorithm, the epigraph code is
much faster, and in some cases, provides a
mathematically optimal solution.
In addition, Korber is working with experimentalist colleagues at Duke and Harvard
on two other projects that they have not
yet published research on. One is called a
Signature-informed Epitope Targeting, or
“It’s an idea where you look at the evo-
lution of the viruses, and how that impacts
how sensitive viruses are to antibodies, and
then you design vaccines based on anti-
body activity and resistance patterns,” said
Korber. “It is a quite different approach where
you use a statistical measure to study the
impact of diversity on antibody sensitivity,
and to design vaccines. SET vaccines have
shown some promise in guinea pigs so far,
but we haven’t taken it further than that.”
Another approach she is working on,
known as “structural mosaic,” takes into ac-
count the three-dimensional structure of a
viral protein, as well as the sequence of the
protein, explained Korber. This approach is
also currently being tested in guinea pigs.
Both strategies have yet to be tested for
protection from infection, but Korber is
optimistic about their potential.
Korber doesn’t know if the mosaic vaccine
that is being tested in the Imbokodo trial—
or any of her other ongoing projects— will
result in a successful HIV vaccine, but she is
hopeful either way. For Korber, even a failed
idea is a worthwhile experience.
“If it does work that is wonderful, especially
if it works to a level where it is actually useful
enough to make it as a product,” said Korber.
“If this doesn’t work we will learn from the trial
anyway and we will learn why it didn’t work,
maybe, and be able to do better the next trial.
And meanwhile, both my laboratory and my
colleague’s laboratories have other horses in
the race. Either way it’s exciting.”
Preclinical studies with the mosaic-based
vaccine regimen confirmed this, demon-
strating that they were effective in protecting
monkeys against infection with an HIV-like
virus. Then two early-stage human clinical
trials suggested that these vaccines are
well-tolerated and can generate anti-HIV im-
mune responses in healthy adult volunteers.
As a result, the National Institutes of
Health (NIH) launched a large clinical trial
in November 2017 to assess whether the
mosaic HIV vaccine regimen is safe and
able to prevent HIV infection in humans.
The study is sponsored by Janssen Vac-
Johnson, with co-funding from two primary
partners, the Bill & Melinda Gates Founda-
tion and NIH’s National Institute of Allergy
and Infectious Diseases. The new Phase IIb
proof-of-concept study, called Imbokodo,
aims to enroll 2,600 HIV-negative women
in sub-Saharan Africa. The first Imbokodo
participants received vaccinations at clini-
cal research sites in South Africa, followed
by participants in Malawi, Mozambique,
Zambia, and Zimbabwe. Participants will be
followed for at least two years.
Although Korber herself has stepped
away from the clinical trial portion of this
research, she is still closely watching its
progress. She serves as an advisor for the
project for both Barouch and Janseen.