HIV transmission and spread in the host are based on the survival of the virus or infected cells present in mucosal secretions, and the virus' ability to cross the epithelial barrier and access immune target cells, which leads to systemic infection. Therefore, HIV-specific immunity at mucosal sites is critical for control of infection. Although mucosal delivery would ensure the best onset of protective immunity, most candidate vaccines are administered through the parenteral route. Remarkably, secretory IgA (SIgA) interacts specifically with mucosal microfold (M) cells present in gut-associated lymphoid tissues. Here we evaluate the feasibility of delivering chemically bound p24HIV antigen via SIgA into the intestinal mucosae in mice. After oral administration, p24-SIgA complexes are quickly delivered into the tissue and selectively captured by CX3CR1 + dendritic cells. Oral immunization with p24gag linked to SIgA (p24-SIgA) adjuvanted with E. coli heat labile enterotoxin (HLT) elicits both humoral and cellular immune responses against p24 at the systemic and mucosal levels and induces efficient protection against rectal challenge with a recombinant vaccinia virus encoding gag. This is the first study which underscores the remarkable potential of SIgA to serve as a vaccine carrier for an HIV antigen in mucosal administration targeting the gastrointestinal environment.Keywords: HIV vaccine strategy r Microfold cells r Oral vaccination r SIgA reverse transcytosis Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionOral delivery of vaccines is an attractive mode of immunization because of its high acceptability and convenience of use. Moreover, the GALT plays a central role in the induction of immunity and homeostasis to infectious agents. In Peyer's Patches (PPs), DCs are separated from the intestinal lumen by the follicle-associated epithelium (FAE), allowing the transfer of pathogens to under- Results and discussionSpecific uptake and transport of p24-SIgA across murine FAEWe sought to assess whether association of p24 with SIgA can improve the delivery of antigen across the FAE of PPs. Administration into intestinal ligated loops revealed the presence of p24-SIgA in the SED region of PPs (Fig. 1A), whereas no localization of p24 administered alone could be detected above background in PPs (Fig. 1B). Moreover, p24-SIgA complexes, besides to be taken up by Dectin-1 + M cells [3], were found in close association with DC-SIGN + ( Fig. 1C) and CX3CR1 + (Fig. 1D) DCs present in the SED region, as illustrated by the appearance of yellow dots. In contrast, green DCs in the SED region and red p24 located in the lumen were only detected when the antigen was delivered alone (Fig. 1E). This finding prompted us to investigate whether oral immunization with p24-SIgA complexes can induce subsequent p24-specific intestinal and systemic immune responses. p24-Specific Ab responses after oral administration of p24-SIgA complexesPostoral immunization, p24-sp...

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International audienceZinc(II) stabilized polyelectrolyte nano-complexes (PECs) of chitosan and hyaluronan (HYA) were designed as safe and efficient drug delivery systems. HIV-1 reverse transcriptase inhibitor tenofovir (TF) was quantitatively encapsulated and the particle interface could be functionalized in PBS with targeting proteins such as anti-alpha 4b7 immunoglobulin A. Chitosan-HYA nanoPECs were non-cytotoxic on human peripheral blood mononuclear cells (PBMCs), within the investigated nanoparticle concentrations. A dose-dependent reduction of the HIV-1 infection of PBMCs co-cultured with the nanocarriers was observed. Even more interestingly, a synergistic effect was evidenced with the nanocarriers by comparing the IC50 (50% inhibitory concentration) value of the aqueous TF solution (4.35 mu mol L-1) with that of TF loaded nanoPECs (1.71 mu mol L-1) and anti-a4b7 IgA functionalized TF/nanoPECs (1.01 mu mol L-1). This effect could be attributed to the presence of zinc(II) in the formulation of the colloids. All these data establish that the zinc(II) stabilized chitosan-HYA nanoPECs can be potentially efficient and safe colloidal delivery system candidates for enhancing antiviral activities in the treatment of HIV infection and AIDS