Abstract
The development of new and effective adjuvants may play a fundamental role in improving HIV vaccine efficacy. New classes of vaccine adjuvants activate innate immunity receptors, notably toll like receptors (TLRs). Adjuvants targeting the C-Type lectin receptor DC-SIGN may be alternative or complementary to adjuvants based on TRL activation. Herein we evaluate the ability of the glycomimetic DC-SIGN ligand Polyman 19 (PM 19) to modulate innate immune responses. Results showed that PM 19 alone, or in combination with TLR agonists, induces the expression of cytokines, β chemokines and co-stimulatory molecules that may, in turn, modulate adaptive immunity and exert anti-viral effects. These results indicate that the suitability of this compound as a vaccine adjuvant should be further evaluated.
Highlights
Several efforts are needed to develop an effective and safe vaccine against AIDS
In particular we investigated whether this compound could induce activation of early innate immune responses, with the aim of developing carbohydrate dendritic cells (DCs)-SIGN ligands as adjuvants
We have recently demonstrated that Polyman 19 (PM 19), a polyvalent dendrimer carrying six units of a bisamide-based DC-SIGN ligand (Figure 1), completely inhibits HIV-1 Bal trans infection of
Summary
Several efforts are needed to develop an effective and safe vaccine against AIDS. The use of live attenuated viruses is not feasible in humans for safety concerns. Vaccines based on protein subunits are scarcely immunogenic. Other approaches are based on DNA vaccines or live recombinant vectors encoding HIV-1 antigens to enhance cell mediated immunity (CMI). Prime-boost strategies, that use a combination of different types of vaccines to generate strong CMI and humoral immune responses, have been developed [1]. Clinical trials based on this approach have not so far produced the desired results. The prime-boost combination of vaccines used in the RV144 trial demonstrated only a limited preventative effect [2].
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