An HIV vaccine that had previously been tested and demonstrated to reduce the virus’s acquisition rate has again been proven effective against a similar pathogen in Old World monkeys in a new trial led by doctors at the Case Western Reserve University School of Medicine.
However, while the new research, which was led by immunopathogenesis professor Dr. Rafick-Pierre Se´kaly, was able to replicate results from a previous RV144 vaccine trial, it also revealed that replacing the alum adjuvant – a substance often found in non-living vaccines that can induce antibody-mediated immunity – with a stronger agent would not produce a better vaccine.
Dr. Sekaly and his colleagues tested RV144 on rhesus macaques, and found that the combination of the vaccine and the original alum adjuvant reduced the acquisition rate of the HIV-like simian immunodeficiency virus (SIV) by 44 percent. In previous studies involving humans, RV144 was shown to have a 31 percent efficacy, the study authors explained Thursday in a statement.
However, when they replaced the alum adjuvant with MF59, which has been shown to stimulate immune response in the human body, they found that the results were not significantly better. In fact, the altered treatment was unable to prevent SIV acquisition at a greater rate, and could only trigger an immune response at the point of infection, as had been hypothesized.
Unaltered RV144 with alum adjuvant proven most effective
Furthermore, Dr. Sekaly’s team discovered more about how the alum adjuvant acts in the RV144 vaccine: a unique link between an intercellular pathway called Ras-Raf-MEK-ERK (RAS) and RV144 efficacy. Ten of 12 genes associated with this pathway were expressed within the vaccine, they said, and were shown to trigger multiple adaptive responses.
Those responses, in turn, have been associated with a reduced SIV acquisition rate in the group of rhesus macaques that received the alum-vaccine group, the researchers added. Based on these findings, future studies to investigate whether or not RAS activation is involved in the efficacy of HIV vaccines in humans are likely.
“These fascinating clinical results effectively dispel our previous belief that the RV144 vaccine could possibly become more effective with the MF59 adjuvant,” Dr. Sekaly said in a statement. “Instead, we found that the modified vaccine actually triggered the recruitment of innate cells in the site of infection.”
“Through this research, we were able to confirm the efficacy of the current RV144 vaccine in preventing infection by HIV/SIV in macaques, creating an even clearer pathway to the near-term development of this vaccine for human use,” he continued, adding that based on his team’s work, they were able to accurately predict whether or not an animal would respond to the treatment by analyzing their pre-vaccination RNA expression.
In fact, they correctly forecasted the vaccine’s effectiveness in two-thirds of the macaques that were tested. Those results “strongly support the notion that personalized and predictive vaccinology will soon become a reality, including in HIV – a disease area for which this type of precision medicine is desperately needed but has not yet been extensively studied,” the professor concluded.
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