Every day, nearly 300 children are infected with HIV, or more than 100,000 new infections per year, mainly through mother-to-child transmission after birth, through breastfeeding. In resource-limited areas, regular access to antiretroviral treatment and care remains difficult, which compromises prevention.
One of the solutions being considered would be to be able to treat babies immediately after birth with a long-term therapy. It is precisely in this critical niche, when mothers are still consulting after giving birth, that our approach is placed.", underlines Amir Ardeshir, professor of microbiology and immunology.
Muscles transformed into antibody factories
In a study published in the review Nature, researchers from the Tulane National Primate Research Center and the California National Primate Research Center show that treatment given to macaques in their first month of life protected them for nearly three years against the simian immunodeficiency virus, similar to HIV. We exploited a unique property of the newborn's immune system: neonatal tolerance" explains Amir Ardeshir. " At this age, the body more readily accepts foreign agents and considers them as part of itself.“.
The treatment is based on broadly neutralizing antibodies (bNAbs). These are antibodies capable of blocking a wide variety of HIV strains. They recognize conserved areas of the envelope protein that covers the virus, making them effective against several variants. They have been discovered in people nicknamed " elite controllers", whose immune system naturally manages to contain the virus.
Traditionally, bNAbs are administered by infusion, every month or two, which poses logistical challenges, particularly in developing countries. Each infusion requires an injection center, laboratory production and regular monitoring", recalls the biologist.
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The novelty of this study lies in the way these antibodies are administered. We replaced repeated infusions with a single injection of viral vectors", explains Amir Ardeshir. These vectors, derived from a harmless virus, were programmed to deliver the DNA of the bNAbs into muscle cells. " Muscles are abundant, easy to access and above all take a long time to renew themselves." he emphasizes. " They are transformed into micro-factories capable of producing antibodies for decades.“.
Long-lasting efficiency
Tests conducted on newborn macaques revealed protection against infection during simulated exposures. In monkeys treated from birth, we observed functional expression of antibodies for nearly three years", says Amir Ardeshir. " This demonstrates that a single intramuscular injection can confer long-lasting immunity."It could continue into adolescence in humans.
The researchers' next goal is to test this approach in humans. We are first considering clinical trials in children already living with HIV, to try to control the infection without resorting to daily antiretroviral treatment.", he explains. Ultimately, this therapy could also be offered to HIV-negative newborns in areas where mother-to-child transmission remains common. It is not yet known whether the window of tolerance observed in macaques is the same as in humans, but it is thought that it could be a little longer because human babies grow more slowly.“.
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Huge potential beyond HIV
More broadly, the principle of this gene therapy could be applied to other infectious diseases targeting young children. THE malaria, for example, remains a major cause of infant mortality in low-income countries", recalls Amir Ardeshir. " Effective monoclonal antibodies exist but their effectiveness requires frequent boosters. With our technology, we could inject genetic instructions once, at birth, to produce antibodies against the parasites responsible for the disease“.
The obstacle remains the cost of producing viral vectors, which is still high today. But I think it's only a matter of time", the researcher believes. " The auto industry produces 3 cars per minute in the United States. This level of industrialization can be achieved for gene therapy, provided massive investment is made.. What we've achieved was unthinkable ten years ago. Now we have all the tools we need to tackle HIV differently." he concludes.
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