A two-dose HIV vaccine generated antibodies against the virus in 35 out of 36 people (97 per cent), with no severe side effects.
The early-stage trial was designed to demonstrate safety and a proof-of-concept for a relatively novel approach to HIV vaccination. It is unclear whether the vaccine protects against HIV. Based on the antibody levels generated by the two-dose regimen, booster doses are expected to be required.
Developing an HIV vaccine is particularly difficult because the virus rapidly mutates into new strains, which somewhat evade immunity.
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As a result, many groups of researchers are seeking to develop vaccines that stimulate a type of immune cell called B-cells to generate so-called broadly neutralising antibodies. These work against parts of the HIV virus that vary little between strains.
During any viral infection, only a fraction of B-cells that are specific to the virus may make broadly neutralising antibodies.
When it comes to HIV, incorporating viral proteins into a vaccine may activate this subset of B-cells.
To assess the effectiveness of this approach, Juliana McElrath at the University of Washington in Seattle and her colleagues recruited 48 volunteers without HIV to test a vaccine that stimulates B-cells to make HIV-specific broadly neutralising antibodies, based on laboratory and animal studies.
The vaccine contains part of a protein found on the surface of HIV, called gp120, which helps the virus enter cells.
Thirty-six of the participants were given either two low or two high doses of the injected vaccine, administered two months apart. The remaining 12 volunteers, acting as the control group, received a saline solution.
After the injections, all the participants regularly provided blood samples for 16 weeks. Of those who received either the low or high vaccine doses, 97 per cent had HIV-specific broadly neutralising antibodies at the end of the study. Antibody levels were similar across the participants who received either the high or low vaccine doses, but marginally higher among those who had the high doses.
Among the 12 participants who received a saline solution, two had HIV antibodies at the end of the study. Why this occurred is not entirely clear. These participants may have had some natural immunity against the virus.
Across all the participants, including those given the saline solution, 98 per cent experienced mild side effects, such as fatigue, headaches and tenderness at the site of injection.
“This paper described the best B-cell immune response from vaccination against HIV I have seen,” says Gary Kobinger at the University of Texas. “It is thus technically cutting edge in addition to pursuing a completely novel approach to vaccination.”
However, the vaccine hasn’t yet been shown to protect against HIV infection, says Kobinger. Also, based on the level of antibodies generated, more than two doses would probably be needed to prevent infection, he says.
Nevertheless, fine-tuning this approach could help in the development of vaccines against other fast-mutating viruses, such as influenza and dengue.
“If ever this works, it would be a new tool in the arsenal of vaccinologists to counter viruses with high mutation rates,” says Kobinger.
Science DOI: 10.1126/science.add6502
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