Results of a laboratory test on mice may open a promising new path toward a vaccine against HIV, an approach scientists call “vectored immunoprophylaxis” (VIP).
Researchers have been searching for “broadly neutralizing antibodies” (bNAbs) from among the small number of people with an innate ability to resist HIV. So far, this has turned up about 20 bNAbs, but there are unknowns about how they work and whether they can be made vaccine-deliverable.
The research team, led by David Baltimore of the California Institute of Technology (Caltech), said it has developed a way to deliver bNAb-making genes in lab mice genetically modified to be susceptible to HIV infection. Using the VIP approach, the team injected a harmless adeno-associated virus into the leg muscle of mice, where it entered cells and expressed bNAbs into circulation.
The mice were then injected intravenously with one nanogram of HIV, enough to infect most unvaccinated mice, and even eventually 125 nanograms. “We show that humanized mice receiving VIP appear to be fully protected from HIV infection, even when challenged intravenously with very high doses of replication-competent virus,” the authors wrote.
VIP is “like gene therapy, but distinct,” said Baltimore. VIP took up residence in the muscle tissue but did not slot genes into the mouse’s DNA code, he explained. “It’s not an ‘insertion’ but a free plasmid-like element that will exist in muscle cells,” he said.
The researchers stressed that the jump from mice to humans is large. “We’re not promising that we’ve actually solved the human problem,” Baltimore said. “But the evidence for prevention in these mice is very clear.”
Baltimore was co-winner of the 1975 Nobel Prize for Medicine for his work on reverse transcriptase, a key enzyme in the replication of retroviruses, the family which includes HIV.
Results of the study, “Antibody-Based Protection Against HIV Infection by Vectored Immunoprophylaxis,” were published in Nature (2011;doi:10.1038/nature10660).
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