Abstract
Improved vaccine-mediated protection against HIV-1 requires a thorough understanding of the mode of HIV-1 transmission and how various immune responses control transmission. Cell-associated HIV-1 is infectious and contributes to HIV-1 transmission in humans. Non-human primate models of cell-associated SIV infection demonstrate that cell-associated SIV is more infectious than cell-free SIV. In a recently described chimeric simian–human immunodeficiency virus (SHIV) macaque model, it was demonstrated that an occult infection with cell-associated SHIV can be established that evades passive protection with a broadly neutralizing antibody (bnAb). Indeed, considerable in vitro data shows that bnAbs have less efficacy against cell-associated HIV-1 than cell-free HIV-1. Optimizing the protective capacity of immune responses such as bnAbs against cell-associated infections may be needed to maximize their protective efficacy.
Highlights
Immune-based prophylactics and/or vaccines are urgently needed to slow the spread of new HIV-1 infections
A potential ramification of HIV-1 being transmittable as both cell-free virus and cell-associated virus (CAV) is the possibility that free virions and CAV are differentially susceptible to immune-based interventions that are designed to prevent infection
Infection that we observed in an animal following CAV exposure was a ramification of the high-dose challenge employed, we have recently discussed this observation in detail, and noted the need for clinical trials of pre-exposure prophylactics (PrEP) and broadly neutralizing antibody (bnAb)-based passive immunization to carefully watch for such cases in HIV-1 exposed humans [69]
Summary
Immune-based prophylactics and/or vaccines are urgently needed to slow the spread of new HIV-1 infections. Systemic or mucosal passive immunization of macaques with bnAbs protects against in vivo cell-free simian/human immunodeficiency virus (SHIV) challenges [9,10,11,12,13,14,15]. The success of bnAb passive immunization in animal models has motivated attempts to passively establish these antibodies in humans at risk of HIV-1 infection. Further studies will likely be highly informative for designing vaccines and/or immune-based prophylactics that are capable of robustly preventing infection with both cell-free virus and CAV. This manuscript reviews the evidence of CAV involvement in viral transmission, as well as the capacity of CAV to evade antibody neutralization. We examine opportunities for future research that will drive the optimization of bnAb prevention of CAV transmission, leading to the development of strategies to prevent infection by both cell-associated and cell-free virus
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