Incorporation of Innate Immune Effector Mechanisms in the Formulation of a Vaccine Against HIV-1

Abstract

The realization of a major role for events that occur during acute viremia that dictate the course of disease both in HIV-1 infected humans and susceptible SIV infected non-human primates has prompted an intense interest in studies of the contribution of innate immune effector mechanisms. It is reasoned that findings from such studies may be important and need to be incorporated into the design and formulation of potential candidate vaccines against HIV-1. This review serves to outline the various non-human primate models that can best serve to address this issue, a summary of our knowledge on the various subsets of NK cells (one of the major innate immune cell lineage) that have an impact on the course of disease, the potential pathways that regulate their function and the potential role of the KIRs on SIV-induced disease course. Finally, the major points from this report and the data presented on similar subjects by other investigators is utilized to provide a summary of the potential future directions that we need to take in efforts to move this field forward.

Antiretroviral therapy partly reverses the systemic and mucosal distribution of NK cell subsets that is altered by SIVmac251 infection of macaques

“…Our lab and others have shown that SIV infection of Rhesus macaques is a valuable tool to mimic natural HIV infection in humans (Pegu, Vaccari et al, 2012; Morgan, Marthas et al, 2008; Ansari, Mayne et al, 2011). The majority of HIV infections are acquired through sexual transmission, thus HIV enters the body through the vaginal, rectal, or penile mucosa.…”

“…The early phase of HIV infection is critical as the outcomes of the interaction between the virus and the immune system during this phase is likely to determine whether the virus is eliminated, locally controlled, or disseminates to the rest of the body (Naranbhai, Altfeld et al, 2013; Ansari, Mayne et al, 2011). While it is clear that there is a rapid activation of innate immune responses after viral exposure (Chang & Altfeld, 2010; Haase, 2010) details on innate cell types and their role in the immune responses to HIV remains unclear.…”

“…Within few days however, the virus disseminates systemically and a persistent infection is established (Haase, 2005; Hladik & Hope, 2009; Yu & Vajdy, 2010). Recent reports suggest that the role of innate immune components, present at the mucosal site during this early phase of the infection, may determine the disease outcome (Borrow, 2011; Ansari, Mayne et al, 2011). …”

“…Rhesus macaque peripheral blood NK cells are generally defined as CD3 − CD20 − CD8αα + and NKG2A + . NK cells can be further subdivided into three groups depending on the degree of CD56 and CD16 receptors expression (Reeves, Gillis et al, 2010; Hong, Rajakumar et al, 2013; Ansari, Mayne et al, 2011). …”

“…In contrast, the CD16 − CD56 − (DN subset) may have both properties (Webster & Johnson, 2005; Pereira, Johnson et al, 2008; Ansari, Mayne et al, 2011). …”