Finding points the way toward a successful vaccine
Duke University Medical Center
An HIV vaccine candidate developed at the Duke Human Vaccine Institute triggered low levels of an elusive type of broadly neutralizing HIV antibodies among a small group of people enrolled in a 2019 clinical trial.
The finding, reported May 17 in the journal Cell,
not only provides proof that a vaccine can elicit these antibodies to fight
diverse strains of HIV, but that it can also initiate the process within weeks,
setting in motion an essential immune response.
The vaccine candidate targets an area on the HIV-1 outer
envelope called the membrane proximal external region (MPER), which remains
stable even as the virus mutates. Antibodies against this stable region in the
HIV outer coat can block infection by many different circulating strains of
HIV.
"This work is a major step forward as it shows the feasibility of inducing antibodies with immunizations that neutralize the most difficult strains of HIV," said senior author Barton F. Haynes, M.D., director of the Duke Human Vaccine Institute (DHVI).
"Our next steps are
to induce more potent neutralizing antibodies against other sites on HIV to
prevent virus escape. We are not there yet, but the way forward is now much
clearer."
The research team analyzed data from a phase 1 clinical
trial of a vaccine candidate developed by Haynes and S. Munir Alam, Ph.D., at
DHVI.
Twenty healthy, HIV-negative people enrolled in the
trial. Fifteen participants received two of four planned doses of the
investigational vaccine, and five received three doses.
After just two immunizations, the vaccine had a 95% serum
response rate and a 100% blood CD4+ T-cell response rate -- two key
measurements that demonstrated strong immune activation. Most of the serum
responses mapped to the portion of the virus targeted by the vaccine.
Importantly, broadly neutralizing antibodies were induced
after just two doses.
The trial was halted when one participant experienced a
non-life-threatening allergic reaction, similar to rare incidents reported with
COVID-19 vaccinations. The team investigated the cause of the event, which was
likely from an additive.
"To get a broadly neutralizing antibody, a series of events needs to happen, and it typically takes several years post-infection," said lead author Wilton Williams, Ph.D., associate professor in Duke's Department of Surgery and member of DHVI.
"The
challenge has always been to recreate the necessary events in a shorter space
of time using a vaccine. It was very exciting to see that, with this vaccine
molecule, we could actually get neutralizing antibodies to emerge within
weeks."
Other features of the vaccine were also promising, most
notably how the crucial immune cells remained in a state of development that
allowed them to continue acquiring mutations, so they could evolve along with
the ever-changing virus.
The researchers said there is more work to be done to
create a more robust response, and to target more regions of the virus
envelope. A successful HIV vaccine will likely have at least three components,
all aimed at distinct regions of the virus.
"Ultimately, we will need to hit all the sites on the envelope that are vulnerable so that the virus cannot escape," Haynes said. "But this study demonstrates that broadly neutralizing antibodies can indeed be induced in humans by vaccination. Now that we know that induction is possible, we can replicate what we have done here with immunogens that target the other vulnerable sites on the virus envelope."