A new
potential mRNA vaccine that delivers instructions for making two key HIV
proteins has been tested in mice and rhesus macaques.
A team from the US National Institutes of Health’s
(NIH) National Institute of Allergy and Infectious Diseases (NIAID) has
developed and tested a messenger RNA (mRNA) HIV vaccine in
animals, with promising results.
The researchers say that the experimental HIV
vaccine is injected into muscle, where it delivers instructions for making two
key HIV proteins, Env and Gag. Muscle cells assemble these two proteins into
virus-like particles that are studded with many copies of Env on their surface.
These virus-like particles cannot cause infection or disease because they lack
the complete genetic code of HIV, but they provoke immune responses similar to
natural HIV infection.
The team first tested the vaccine in mice, as
outlined in their paper published in Nature Medicine.
They found that, after two injections, it elicited antibodies in all animals
that could neutralise HIV. The Env proteins on the virus-like particles
produced from the vaccine closely mimicked natural infection. According to the
researchers, this represents an improvement over previous experimental HIV
vaccines.
They
then tested the vaccine in rhesus macaques. The monkeys received a priming
vaccine followed by several booster inoculations. By week 58, all vaccinated
macaques had developed measurable levels of antibodies that could neutralise
many diverse HIV strains. The experimental vaccine also induced other important
immune responses, like helper T cells, which aid other immune cells.
The macaques were then exposed weekly to
simian-human HIV (SHIV), a form of the virus used for modelling human HIV in
monkeys. After 13 weeks of virus inoculations, two out of seven immunised
macaques remained uninfected. The other immunised animals had a delay in
infection, which occurred after eight weeks, on average. In contrast,
unimmunised animals became infected on average after three weeks. Overall,
vaccinated monkeys had a 79 percent lower per-exposure risk of SHIV infection
than unvaccinated animals.
The team also found that the vaccine course was
well-tolerated with only mild side effects. These results showed that the novel
HIV vaccine was safe and prompted immune responses against an HIV-like virus.
“Despite nearly four decades of effort by the
global research community, an effective vaccine to prevent HIV remains an
elusive goal,” said Dr Anthony Fauci, NIAID director and co-author of the
study. “This experimental mRNA vaccine combines
several features that may overcome shortcomings of other experimental HIV
vaccines and thus represents a promising approach.”
The team plans to conduct a Phase 1 trial of the
mRNA HIV vaccine in healthy adult volunteers after further refinement and
testing.