Survivors Remorse: antibody‐mediated protection against HIV‐1

Abstract

Summary It is clear that antibodies can play a pivotal role in preventing the transmission of HIV-1 and large efforts to identify an effective antibody-based vaccine to quell the epidemic. Shortly after HIV-1 was discovered as the cause of AIDS, the search for epitopes recognized by neutralizing antibodies became the driving strategy for an antibody-based vaccine. Neutralization escape variants were discovered shortly thereafter, and, after almost three decades of investigation, it is now known that autologous neutralizing antibody responses and their selection of neutralization resistant HIV-1 variants can lead to broadly neutralizing antibodies in some infected individuals. This observation drives an intensive effort to identify a vaccine to elicit broadly neutralizing antibodies. In contrast, there has been less systematic study of antibody specificities that must rely mainly or exclusively on other protective mechanisms, although non-human primate (NHP) studies as well as the RV144 vaccine trial indicate that non-neutralizing antibodies can contribute to protection. Here we propose a novel strategy to identify new epitope targets recognized by these antibodies for which viral escape is unlikely or impossible.

Immunomodulatory Nanosystems

“…[264] Moreover, long-term treatment can also develop a variety of side effects, including lipodystrophy, hyperlipidemia, and damage to the liver and immune system. [266] In this case, nanomaterials can enhance the therapeutic effect of HIV vaccine as adjuvants or carriers. Scientists have suggested that HIV vaccine might be a new hope to eliminate virus by boosting immune response.…”

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

“…However, there is little direct evidence that nnAbs exert selective pressure on HIV-1 during infection in vivo (Burton et al, 2011; Chung et al, 2011; Santra et al, 2015). Vaccination studies in non-human primates (NHP) have suggested a role for non-neutralizing immune responses in protection against SIV or SHIV infection, but a causal link has not been proven experimentally (reviewed in (Lewis et al, 2017)). In these NHP studies, different vaccination strategies induced nnAb responses that correlated with protection from infection (Barouch et al, 2015; Barouch et al, 2013; Demberg et al, 2007; DeVico et al, 2007; Florese et al, 2009; Fouts et al, 2015; Hidajat et al, 2009).…”

Targeting the Late Stage of HIV-1 Entry for Antibody-Dependent Cellular Cytotoxicity: Structural Basis for Env Epitopes in the C11 Region

“…Previously, we defined Epitope Cluster A as a potent ADCC target recognized by CD4i mAbs (Guan et al, 2013). Epitope Cluster A maps to the inner domain and the extended N-, C-termini of gp120 ((Acharya et al, 2014; Gohain et al, 2015) and reviewed in (Lewis et al, 2014; Lewis et al, 2017a; Veillette et al, 2016)). Antibodies specific for Cluster A epitopes were shown to mediate the majority of the ADCC activity detected in chronically-infected individuals (Ferrari et al, 2011; Guan et al, 2013; Veillette et al, 2014) as well as being implicated in protection for the clinical RV144 vaccine trial (Bonsignori et al, 2012; Haynes et al, 2012; Tomaras et al, 2013) and our SHIV challenge studies in rhesus macaques (DeVico et al, 2007; Fouts et al, 2015) immunized with a gp120 transition state vaccine (Fouts et al, 2000).…”