Autoimmune Disease Protectant May Elicit HIV Broadly Neutralizing Antibodies

The same process that protects the body from autoimmune diseases could also facilitate the production of broadly neutralizing antibodies (bnAbs) in patients with HIV, a recent study shows.

Immunological tolerance is a process in which the immune system is unresponsive to the body’s own antigens. B cells that carry self-reactive antibodies are eliminated while still in development in the bone marrow. Those that do escape are generally suppressed by the immune system.

In a study published in the Journal of Experimental Medicine, investigators sought to examine whether breaking the immunological tolerance mechanisms to allow the production of self-reactive antibodies would aid bnAbs production.

The investigators used mice with genetic defects that cause lupus-like symptoms and injected them with alum, a chemical that promotes antibody secretion. The results of the study showed that most of the mice produced antibodies that could neutralize HIV-1.

Healthy mice were then treated with a drug that impairs immunological tolerance. The mice began producing antibodies somewhat capable of neutralizing HIV-1, and the production increased after the alum injection. Mice injected with the HIV-1 protein Env produced bnAbs that could neutralize a variety of HIV-1 strains, according to the study.

The production of HIV-1 neutralizing antibodies correlated with self-reactive antibody levels, which recognize Histone H2A. The investigators purified the anti-H2A antibodies, confirming their ability to neutralize HIV-1.

“We think this may reflect an example of molecular mimicry where HIV-1 Env has evolved to mimic an epitope on histone H2A as a mechanism of immune camouflage,” said lead investigator Raul M. Torres.

The immunological tolerance process eliminates or suppresses any B cells that can produce antibodies that recognize histone H2A, ultimately reducing the production of bnAbs.

“But breaching peripheral immunological tolerance permits the production of cross-reactive antibodies able to neutralize HIV-1,” Torres. “As this study was performed in an animal model, it will of course be important to determine its relevance for HIV immunity in humans. Here, primary consideration will be determining whether immunological tolerance can be transiently relaxed without leading to detrimental autoimmune manifestations and as a means to possibly elicit HIV-1 bnAbs with vaccination.”