Controling HIV-like virus in monkeys by early intervention

HIV photo-Optimized

The paper was published in Nature on March 13.

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.

Published in The Hindu on March 14, 2017

Editorial: Gene therapy offers fresh hope

Published in The Hindu on December 14, 2011

While a quarter century of single-minded effort to find an efficacious HIV vaccine has met with only a limited success, a team of researchers led by Nobel Laureate David Baltimore has obtained promising results in prevention of HIV infection in mice by adopting a radically different approach. They deployed gene therapy, which is traditionally used for curing genetic diseases. The study builds on the seminal work by Phil Johnson from the Children’s Hospital of Philadelphia who first showed how gene therapy protects monkeys from SIV, a virus that is analogous to HIV. The results of the study were published recently in Nature As a first step, genes from five broadly neutralising antibodies capable of preventing HIV infection were chosen. DNA, which code for the antibodies, were then inserted into the adenovirus-based vectors and injected into the leg muscles of the mice. The muscle cells containing the DNA eventually started producing the broadly neutralising antibodies. Surprisingly, two antibodies were able to prevent HIV infection even when the viral dose was a 100-fold higher than necessary to infect animals, and significantly more than what humans are likely to be exposed to. As the level of protection in mice remained high even at the end of one year, it is presumed that a single injection might be sufficient to produce long-lasting protection against HIV. Clinical trials on humans may follow soon.

While preventive vaccines containing an immunogen (antigen) prime the immune system to produce antibodies against a virus well before the body is naturally exposed to it, the new approach completely bypasses the immune system and presents the body with DNA capable of producing potent antibodies. But the real differentiator is the speed in designing and developing an effective immunisation product. For instance, the antibodies used in the current study are based on more than a dozen broadly neutralising antibodies isolated from HIV-infected individuals who were not on antiretroviral therapy. While the vaccine programme based on these antibodies is yet to design an effective immunogen, scientists using gene therapy have already completed animal studies. Despite the impressive results, there is sufficient reason to be cautious. Similar levels of success may not be seen in humans. But most importantly, once introduced into the body, there is no way of removing the DNA or turning them off, should things go wrong.