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People living with HIV who naturally produce broadly neutralizing antibodies (bNAbs) that may help suppress the virus have different immunological profiles than people who do not, researchers report. While bNAbs cannot completely clear HIV infections in people who have already acquired the virus, many scientists believe a successful preventive HIV vaccine must induce bNAbs. The new findings indicate that bNAb production may be associated with specific variations in individual immune functions that may be triggered by unchecked HIV infection. Defining how to safely replicate these attributes in HIV-uninfected vaccine recipients may lead to better designed experimental vaccines to protect against HIV. The study was supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.
Researchers led by a team at Duke University identified these immunologic variations by studying blood samples collected from people living with HIV by the NIAID-supported Center for HIV/AIDS Vaccine Immunology (CHAVI). The team compared blood samples from the 51 individuals with the highest level of bNAbs with samples taken from 51 individuals with few or no bNAbs present. The analysis performed revealed that many variations in immune cell function triggered by chronic HIV infection are associated with high levels of bNAbs. The specific changes included a higher frequency of antibodies that attack one's own cells, called autoantibodies; fewer immune regulatory T cells, which were also less active in these individuals; and a higher frequency of memory T follicular helper immune cells.
With this immune system configuration, the activity of antibody-producing immune cells called B cells may be less restricted because they are supported by T follicular helper cells and may be hindered by regulatory T cells. This, in turn, could lead to more efficient production of protective bNAbs against HIV. These findings support approaches to developing an HIV vaccine that involve modifying an individual's immune system to mimic these conditions through the addition of vaccine boosters called adjuvants or other means.
Reference: Moody M, et al. Immune perturbations in HIV-1-infected individuals who make broadly reactive neutralizing antibodies. Science Immunology DOI: 10.1126/sciimmunol.aag0851 (2016).
NIH/National Institute of Allergy and Infectious Diseases