A dendritic cell targeted vaccine induces long-term HIV-specific immunity within the gastrointestinal tract

Abstract

Despite significant therapeutic advances for HIV-1 infected individuals, a preventative HIV-1 vaccine remains elusive. Studies focusing on early transmission events, including the observation that there is a profound loss of gastrointestinal (GI) CD4+ T cells during acute HIV-1 infection, highlight the importance of inducing HIV-specific immunity within the gut. Here, we report on the generation of cellular and humoral immune responses in the intestines by a mucosally administered, dendritic cell (DC) targeted vaccine. Our results show that nasally delivered α–CD205-p24 vaccine in combination with polyICLC, induced poly-functional immune responses within naso-pulmonary lymphoid sites that disseminated widely to systemic and mucosal (GI tract and the vaginal epithelium) sites. Qualitatively, while α–CD205-p24 prime-boost immunization generated CD4+ T cell responses, heterologous prime-boost immunization with α–CD205-p24 and NYVAC gag-p24 generated high levels of HIV-specific CD4+ and CD8+ T cells within the GI tract. Finally, DC targeting enhanced the amplitude and longevity of vaccine induced immune responses in the GI tract. This is the first report of a nasally delivered, DC targeted vaccine to generate HIV-specific immune responses in the GI tract and will potentially inform the design of preventative approaches against HIV-1 and other mucosal infections.

Heterologous prime-boost vaccination protects against EBV antigen–expressing lymphomas

“…This is consistent with other studies using different methods to assess the level of antigen presentation (45). However, vaccination by antigen targeting to the DC receptor DEC205 elicits, with the exception of hen egg-derived model antigens, mostly CD4 + T cell responses in vivo (21,22,(46)(47)(48)(49)(50)(51)(52)(53)(54). This CD4 + T cell bias also led to only modest efficacy after DEC205-targeted NY-ESO1 vaccination, with tumor regression seen in only 2 of 45 patients (55).…”

Adjuvants: Classification,Modus Operandi, and Licensing

“…Several ongoing clinical trials ( Table 2 ) are evaluating poly-ICLC for immunotherapy in patients with cancer [ 58 ]. More recently, poly-ICLC was also nasally delivered with a chimeric antibody containing HIV-p24 protein in mice and induced gastrointestinal immune responses [ 84 ].…”

Direct Delivery of Antigens to Dendritic Cells via Antibodies Specific for Endocytic Receptors as a Promising Strategy for Future Therapies

“…It was also shown that DEC205 or DCIR2 antibodies can be utilized under immunostimulatory conditions to induce protective cellular and humoral responses in vivo needed for the fight against pathogens and malignancies [ 3 , 170 , 179 , 180 , 182 ]. This has, for example, been shown for Yersenia pestis [ 182 ], Plasmodium yoelii [ 180 ], dengue virus [ 171 ], HIV [ 183 , 237 ], the cancer/testis antigen 1A (known as CTAG1A or NY-ESO-1), or the Her2/neu breast cancer antigen in a protective model with NT2.5 tumor cells [ 189 ]. Interestingly, Neubert, et al could demonstrate the induction of both protective and therapeutic anti-tumor responses in a murine melanoma model, which was independent of the initially targeted DC subset [ 179 ].…”