CalTech pushes farther into HIV-prevention with new gene therapy delivery
The study shows that boosting the production of some broadly neutralizing antibodies can protect humanized mice from both intravenous and vaginal infection with HIV.
Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, explained to BioPharma-Reporter.com that the technique is different from other prospective antibody therapies because the “vector that contains the genes for the antibody are not passively transferred.”
As far as the timeline for when the gene therapy might be available, Fauci said it’s still too early to determine and that it depends on the interactions between the US FDA and the CalTech scientists.
“It’s a very interesting and potentially important approach to the prevention of HIV, but as far as timelines…it’s a gene therapy, so they have to make sure all I’s are dotted and t’s crossed,” Fauci said.
New manufacturing paradigm
But the new delivery method, known as Vectored ImmunoProphylaxis (VIP), is not a vaccine so the manufacturing of the vectors will be different from vaccine manufacturing, Fauci said. Vaccines introduce substances such as antigens to try to get an immune system response, whereas VIP delivers genes to muscle tissue to generate specific antibodies from the patient’s immune system.
For the study, investigators inserted genes encoding a broadly HIV neutralizing antibody into a vector – a virus that infects mice but does not cause disease. The researchers then repeatedly exposed the mice to low doses of HIV in a manner that mimics human sexual intercourse. In two separate experiments, the investigators assessed protection from infection with two strains of HIV: a standard laboratory strain as well as one that is commonly transmitted among humans.
Two of the 10 mice expressing the NIH-discovered antibodies became infected with the laboratory strain of HIV after 13 to 15 exposures to the virus, whereas all nine mice without the antibodies were infected with HIV within six exposures.
In a second experiment, researchers used a modified form of the antibody, known as VRC07, and challenged the mice with an HIV strain known to be heterosexually transmitted among people.
The mice expressing the VRC07 antibody were completely resistant to infection during repeated intravaginal challenge. The results indicate that VIP can protect mice from infection with strains of HIV that cause human disease and suggest that a similar strategy could be developed to reduce transmission in people, the authors write.
“The data are very impressive and the story is elegantly done, and the experiments are quite well done,” Fauci said.
He also mentioned a study published in Nature Medicine from 2009 in which researchers performed a vector-mediated gene transfer in monkeys with SIV (Simian immunodeficiency virus), which is similar to HIV. But Fauci noted that this study from 2009 is not as “physiologically relevant” as the CalTech study, which was co-authored by Nobel laureate David Baltimore. Dr. Baltimore did not respond to a request for comment.
“What they were able to do was to challenge the mouse with real HIV, not a different virus that’s like HIV,” Fauci added.
