Remember the landmark RV144 study in Thailand a decade ago that was the first clinical trial to show any efficacy of a vaccine for preventing HIV infection? Now, a team of scientists led by the Fred Hutchinson Cancer Research Center and the University of the Witwatersrand in Johannesburg has found the same regimen can also induce promising immune responses in South Africans, suggesting the vaccine may have the potential to protect against multiple strains of HIV.
In Thailand, the predominant HIV strain is clade B, while clade C is the most common subtype in South Africa. In the new trial, scientists found the RV144 vaccine—containing constructs of HIV clades B and E inserts—showed even higher cellular and humoral immune responses in healthy people in South Africa than in RV144’s Thailand vaccines, according to results published in Science Translational Medicine.
HIV is notorious for its diversity and tendency to mutate, which already makes treating the virus difficult. The same challenge holds true for vaccine development. That’s why the Fred Hutchinson-led team set out to test the RV144 regimen in South Africa and compared immunogenicity data to those from the Thailand study.
One hundred healthy adults participated in the trial, and 91 received all four vaccinations. The researchers evaluated the magnitude and frequency of several immune responses that correlate to infection risk.
Specifically, the vaccine induced strong CD4+ T cells directed at HIV envelope proteins in 51.9% of South Africans, significantly higher than the 36.4% seen in the Thailand trial. And the South Africans' T cells also scored better on a functionality assay that evaluates how good the cells are at producing cytokines.
They looked at the immunoglobulin G (IgG) antibody responses, and participants in the current trial performed better across the board than those from the original RV144 study. They also examined the antibody-dependent cellular cytotoxicity (ADCC), in which immune cells rupture the target cell. Previously, the efficacy of RV144 was correlated with ADCC. Turns out, 72.6% of the trial participants in South Africa responded in the current trial, versus 58.5% of those in Thailand
Back in 2009, RV144 showed just 31.2% effectiveness by month 42. Since then, a variety of research teams have been trying to achieve better protection against as many strains of HIV virus as possible. Scientists led by Duke University previously built on the regimen by adding three more targets to the vaccine construct, making it a pentavalent vaccine. In a study in monkeys, the vaccine achieved 55% protection. Johnson & Johnson recently started testing a different HIV vaccine in a 3,800-person late-stage clinical trial.
The newly reported trial was a precursor to a trial that tested an adapted regimen including subtype C antigens and an adjuvant from GlaxoSmithKline in 252 South African participants. Based on positive interim results from HVTN 100, the National Institutes of Health pushed the new regimen into a large-scale trial that aims to enroll 5,400 men and women, also in South Africa.
The Fred Hutchinson and Johannesburg team did report that the T-cell and antibody responses dropped over time during the trial, “suggesting the utility of additional boosts,” they argued in the study.
But the vaccine’s ability to provide protection against multiple strains of HIV was key, they added. “Our data suggest that the breadth of immune responses elicited by this vaccine regimen may allow for vaccine protection that could extend beyond the clade used for immunogen development, and potentially function as a more global vaccine,” they wrote in the study.