Table 2 Strategies for targeting innate immunity to combat HIV infection and research priorities to advance their development

A. Development of microbicides and passive protection strategies that mediate defence at mucosal infection sites via deployment or local modulation of innate immunity

Structure-function studies to enable the design of small molecules that selectively induce the HIV-inhibitory properties of defensins, WAPs, etc

Identify the key mechanisms involved in type 1 IFN-mediated inhibition of HIV replication so that the pathways involved can be selectively invoked to block viral infection

Evaluate the effect of local administration of immunosuppressive agents at mucosal exposure sites on HIV acquisition

B. Design of vaccines to prime adaptive responses that mediate protection via modulation of innate effector functions

Clarify the importance of ADCVI activity as a means of antibody-mediated control of HIV infection; and Define the key characteristics of antibodies that induce strong ADCVI activity (e.g. isotype, glycosylation status, specificity, affinity)

Verify the existence of HIV-specific Treg cells and determine their in vivo roles, particularly their impact on generalised immune activation

C. Creation of strategies for achieving protection by directly inducing long-term alterations in innate subsets and/or their functions

Characterise NK cell memory in humans (e.g. NK populations involved, longevity, modes of induction); and Identify the ligands on HIV-infected cells that trigger NK cells mediating protective functions, to enable design of immunogens to stimulate these NK subsets

Analyse the roles of NKT cell subsets in protection versus pathogenesis during HIV infection, to determine the utility of targeting these cells in vaccine design

Explore the effects of persisting vaccine vectors on local and/or systemic innate responses