HIV antibodies for treatment of HIV infection

Abstract

Summary The bar is high to improve on current combination antiretroviral therapy (ART), now highly effective, safe, and simple. However antibodies that bind the HIV envelope are able to uniquely target the virus as it seeks to enter new target cells, or as it is expressed from previously infected cells. Further, the use of antibodies against HIV as a therapeutic may offer advantages. Antibodies can have long half-lives, and are being considered as partners for long-acting antiretrovirals for use in therapy or prevention of HIV infection. Early studies in animal models and in clinical trials suggest that such antibodies can have antiviral activity but, as with small molecule antiretrovirals, the issues of viral escape and resistance will have to be addressed. Most promising, however, are the unique properties of anti-HIV antibodies: the potential ability to opsonize viral particles, to direct antibody-dependent cellular cytotoxicity (ADCC) against actively infected cells, and ultimately the ability to direct the clearance of HIV-infected cells by effector cells of the immune system. These distinctive activities suggest that HIV antibodies and their derivatives may play an important role in the next frontier of HIV therapeutics, the effort to develop treatments that could lead to an HIV cure.

Trispecific broadly neutralizing HIV antibodies mediate potent SHIV protection in macaques

“…A variety of broadly neutralizing antibodies (bnAbs) have been isolated from HIV-1 infected individuals (1,2,3), but their potential to treat or prevent infection in humans may be limited by the potency or breadth of viruses neutralized (4,5). The targets of these antibodies have been defined based on an understanding of the HIV-1 envelope structure (6–9).…”

Non-neutralizing Antibodies Alter the Course of HIV-1 Infection In Vivo

“…Moreover, they can suppress established viremia in experimental animals and in humans (Caskey et al, 2015; Caskey et al, 2017; Horwitz et al, 2013; Klein et al, 2012; Scheid et al, 2016) and reviewed in (Margolis et al, 2017). …”

Comprehensive Mapping of HIV-1 Escape from a Broadly Neutralizing Antibody

“…bnAbs are also being tested in both prophylactic and therapeutic settings. Numerous studies in animal models have shown proof-of-concept that passively infused bnAbs can protect against infection (Hessell et al, 2009; Mascola et al, 1999, 2000; Moldt et al, 2012; Parren et al, 2001; Pegu et al, 2014; reviewed in Pegu et al, 2017) and therapeutically suppress viremia during infection (Barouch et al, 2013; Horwitz et al, 2013; Klein et al, 2012; Shingai et al; 2013 reviewed in Margolis et al, 2017). Similar bnAb-based immunotherapies are being tested in humans, with some early studies showing a transient reduction in viral load or delay of viral rebound after treatment interruption in some individuals (Bar et al, 2016; Caskey et al, 2015, 2017; Lynch et al, 2015a; Scheid et al, 2016).…”