Vaccine Provides Comprehensive SHIV Protection in Macaques

While HIV treatment has advanced by leaps and bounds, antiretrovirals’ expense and potential side effects illustrate the continued need for a vaccine option.

The quest for an HIV prophylaxis has yielded some promising news, but such candidates thus far has fallen short. But a new study out of Stanford University using rhesus macaque monkeys highlighted a two-armed approach to vaccination that may prove effective not only against HIV, but against other diseases.

Normally, vaccines stimulate the body to produce antibodies against an infection. It can be difficult to create a vaccine that enables people to produce enough effective antibodies for a long enough period to be fully protective. However, engineering a vaccine that stimulates cellular immunity in addition to antibody production takes the vaccine’s protectiveness to another level.

“The immune system has 2 broadly different arms of host defense: the humoral, or antibody, and the cellular, mediated by T cells,” senior co-author Bali Pulendran, PhD, professor of pathology as well as microbiology and immunology at Stanford, told Contagion®. “[I]t’s...been known that they cooperate, so T cells can help B cells produce antibodies.”

The vaccine candidate created by Pulendran and his colleagues not only enabled the macaques to create antibodies to simian/human immunodeficiency virus (SHIV)—it also increased cellular immunity, providing an additional layer of protection. Cellular immunity involves immune cells targeting and killing any infectious cells that slip past antibodies.

Pulendran illustrated this two-pronged vaccine concept by using a home-invasion analogy.

“Think of the antibodies as guardians standing outside the front door of the house, to prevent entry of the virus into the house,” he said. “It’s a barrier. That is how antibodies prevent viral entry into a cell. Let us suppose that a burglar (the pathogen) does manage to sneak past the antibodies and does gain entry into the house. Then what happens? T cells destroy the whole house.”

In traditional vaccines, the barrier—antibody production—is not always strong enough to prevent the infectious cells from getting inside. Without cell immunity, a person may then become infected. If the vaccine stimulates cell immunity, though, the risk of infection is significantly reduced.

This scenario played out with the 45 female macaques in the trial, who were split into 3 groups of 15. The first group received a series of vaccines to stimulate antibody production. The second group also received the vaccine series plus injections of viruses modified to induce cellular immunity. The third group functioned as a control group.

The monkeys received the vaccines over a period of 40 weeks, then took a 40-week break.

All received booster shots of the antibody-stimulating vaccine and were allowed to rest for another month. At that point, all the macaques received 10 weekly vaginal doses of SHIV.

Twelve out of 15 controls were infected by the time they received their fourth dose of SHIV. In contrast, 8 in the vaccine-only group and 10 in the vaccine-plus-virus-injections group were SHIV-free after 10 doses. The investigators noted that in the monkeys who were infected, the peak viral load was more than 10-fold lower in those who had been vaccinated compared with the controls.

Pulendran said the results support his team’s theory that a vaccine stimulating both antibody production and killer T cells would yield good results.

“They seemed to work hand in hand so that the killer T cells waiting at the [cell] entry point were vigilant,” he said. “They got into action.”

Pulendran noted that a bonus of having a vaccine working on different parts of the immune system is that any antibodies produced don’t need to be as strong as they do with traditional vaccines; pathogens making it past the antibodies will encounter T cells waiting to pounce.

“There’s an army,” he said.

Future studies will build on the investigators’ recent discoveries.

“We need to understand in greater detail exactly how these 2 arms of the immune system are synergizing,” Pulendran explained, speculating that research in this area would take 2-3 years. The team also would like to see whether its findings can be used more widely.

“Although this particular study was focused on HIV, I think we should investigate whether the same principal...could be applied to other infectious diseases such as COVID-19 or malaria,” he said.