Controllers' antibodies
Antibodies to HIV have been studied in people who have interrupted treatment and live without the virus in their blood
Elena Kleshchenko, PCR.news
Among people living with HIV-1, there is a small percentage of so-called controllers after treatment: their body controls the infection even after the interruption of antiretroviral therapy (ART). French researchers led by Dr. Hugo Mouquet from the Pasteur Institute (Paris) studied the humoral (antibody-mediated) immune response in controllers after treatment.
Samples of participants in the VISCONTI (Viro-Immunological Sustained COntrol after Treatment Interruption) study were studied. This is the largest cohort of post-treatment supervisors observed for a long time. The new study included 22 patients who had been receiving ART for at least a year. After discontinuation of therapy, some of them monitored the virus content in the blood for more than 20 years. This means that stable remission in HIV-infected people who have refused regular therapy is, in principle, possible to achieve, and it is important to understand what mechanisms are behind this.
Unlike natural HIV controllers, who spontaneously, without receiving ART, reach low levels of viremia, controllers after treatment rarely have protective HLA class I alleles (for example, HLA-B*57 and HLA-B*27), they also do not have highly effective cytotoxic CD8+T-lymphocytes. Apparently, they, like natural controllers, develop an effective humoral response.
Antibodies and B cells, as well as circulating follicular helper T cells, were studied in patients. It turned out that the profiles of the humoral immune response correlate with the activity of the virus in the human body. Some controllers had short episodes of a slight increase in viremia after discontinuation of treatment. Such short-term exposure to HIV antigens caused a strong humoral response against HIV-1, including the more frequent appearance of memory B cells specific to the envelope protein of the Env virus. These people produced antibodies with a cross-neutralizing effect (against various variants of the virus) and effector antiviral activity (cells of innate immunity destroyed infected cells associated with antibodies). In individual participants, the antibody profile was similar to that observed in elite controllers. In the blood of this group, the number of atypical memory B cells and activated T helper cells increased.
However, there was another group of controllers with a "silent humoral profile": the virus was constantly undetectable in them and a powerful humoral response did not develop; the antibody profile was similar to that observed in HIV-infected people on ART. The mechanisms of viremia control in these patients continue to be studied.
According to Dr. Muke, "early antiretroviral treatment can contribute to the optimal development of a humoral immune response, in some cases counteracting the return of the virus after interruption of treatment." It is unclear, however, whether high levels of antibodies provide control of the virus or they indicate the action of other controlling mechanisms, the authors note.
Article by Molinos-Albert et al. Transient viral exposure drives functionally-coordinated humoral immune responses in HIV-1 post-treatment controllers is published in the journal Nature Communications.
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