In an interesting study, the immune system of monkeys was found capable of controlling HIV-like virus (simian-human immunodeficiency virus (SHIV)) when treatment with a combination of two broadly neutralising antibodies was started three days after infection. The immune system of the animals was found to control the virus even after the anti-HIV antibodies were no longer present in the monkeys.
In a paper published on March 13 in the journal Nature, researchers from the National Institutes of Health and other institutes infected 13 macaque monkeys with SHIV virus. Unlike earlier studies where intervention began late, the researchers started treating the monkeys with two broadly neutralizing HIV antibodies from the third day of infection. The monkeys were infused with the two drugs three times over a two-week period.
Compared with controls, six monkeys were able to suppress the virus for 56 days to as long as six months; in one monkey the virus was below detectable level for 150 days. Once the antibodies level dropped to a very low in the animals, the virus resurfaced. The time taken to rebound was directly related to the concentration of the neutralising antibodies in the plasma.
Quite unexpectedly, five to 22 months after the virus resurfaced, the immune system of the six monkeys spontaneously regained control of the virus and brought it down to undetectable levels for another five to 13 months. Four other monkeys could never fully regain complete control of the virus but the viral load was “very low level” for more than two years. Of the 13 monkeys studied, 10 were able to benefit from two neutralising antibodies administered.
A particular kind of immune cells called CD8+ T cells were found to be higher in all the animals that were infected with SHIV virus. To ascertain if CD8+ T cells were responsible for mediating sustained suppression of virus replication, the researchers purposely depleted the CD8+ T cells in the six monkeys. What followed was a sharp increase in the viral load in all the animals. This helped the researchers conclude that the CD8+ T cells controlled the virus multiplication following the administration of the neutralising antibodies.
The study shows that a combination therapy of two neutralising antibodies given early after infection can control SHIV viral load for nearly six months and facilitate the emergence of potent CD8+ T cells that “durably suppress virus replication”.
Though SHIV infection in macaque monkeys differs from HIV-1 infection in humans in many ways, based on the study, the researchers suggest that immunotherapy should be explored to control the spread of virus, contain the damage to CD8+ T cells, mobilise a robust immune response and control HIV infection in humans.