Anti-HIV Antibodies May Launch New AIDS Therapies

Anti-HIV Antibodies May Launch New AIDS Therapies

Nature just published two studies about new insights on AIDS.

hiv1The HIV virus infects cells of the immune system causing their progressive decrease and weakening the body’s immune reactions to pathogens. As a consequence, HIV patients are much more susceptible to other infections and diseases, including cancer. Current AIDS therapies are mostly based on combinations of antiretroviral drugs that prevent the virus from entering non-infected cells and limit its spread. However, these drugs have no effects on the infected cells that thus continue to produce the virus, or on the virus particles themselves that thus are not destroyed.

Two articles were published this week in Nature by Barouch and colleagues of Harvard University and Scripps Research Institute, and by Shingai and colleagues of the NIH open new possibilities for AIDS treatment. Both groups focused their attention on the intriguing observation that some HIV patients spontaneously develop antibodies that are capable of inactivating the viral particles. Some of these antibodies have been isolated and were tested for their antiviral properties by the two research groups.

Both teams of scientists administered each antibody alone or in combination (a mix of 2 or 3 antibodies) to monkeys infected with the simian-human immunodeficiency virus SHIV, which causes in the animals a disease corresponding to human AIDS. The antibodies rapidly reduced the blood concentration of the virus especially when administered in cocktails, and this effect could last for many days, in certain cases up to several months.

The virus was not completely eliminated though, and in fact it reappeared after some time, in parallel with the reduction of the antibodies’ concentration in the animals. However, a second injection of antibodies at this point effectively decreased the virus titer again, indicating that the surviving virus had not mutated and could still be attacked by the antibodies. In some cases the antibodies were also able to reactivate the animals’ immune system, raising an endogenous antiviral immune response.

Can this therapy work in AIDS patients?

The effects of the antibodies were of variable entity in different animals, at least partly due to the different initial levels of SHIV infection (different initial blood concentration of the virus) in each individual. This variable response can certainly be expected also in human patients.
Moreover, HIV is known to mutate highly, and this means that new resistant variants could rapidly develop in patients during treatment.

Despite these concerns that will have to be confronted, these studies open important new perspectives in AIDS therapy. They demonstrate that AIDS is susceptible to immunotherapy, and strongly encourage testing these antibodies together with the currently used antiretroviral drugs. The two types of therapies in fact have distinct mechanisms of action, and thus their combination could significantly improve AIDS treatment by more strongly reducing and controlling HIV spread in the body.

Reference

Barouch DH, Whitney JB, Moldt B, Klein F, Oliveira TY, Liu J, Stephenson KE, Chang HW, Shekhar K, Gupta S, Nkolola JP, Seaman MS, Smith KM, Borducchi EN, Cabral C, Smith JY, Blackmore S, Sanisetty S, Perry JR, Beck M, Lewis MG, Rinaldi W, Chakraborty AK, Poignard P, Nussenzweig MC, & Burton DR (2013). Therapeutic efficacy of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys. Nature PMID: 24172905

Shingai M, Nishimura Y, Klein F, Mouquet H, Donau OK, Plishka R, Buckler-White A, Seaman M, Piatak M, Lifson JD, Dimitrov D, Nussenzweig MC, & Martin MA (2013). Antibody-mediated immunotherapy of macaques chronically infected with SHIV suppresses viraemia. Nature PMID: 24172896

aids, hiv, therapy, new, monkey, rhesus, antibodies, blood, infection, mutation, virus, immune, immunotherapy

Agnese Mariotti
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