INTRODUCTION

Many diseases and pathologies are associated with a compromised immune system and an increased susceptibility to infectious agents. Patients undergoing surgery, radiation or chemotherapy, and those suffering from autoimmune or other immune deficiency diseases have elevated risk of developing pathological conditions resulting from infection Immune activating strategies can be used to induce immune responses to prevent or combat infection.

Vaccines are widely used to prevent or treat infection by many infectious organisms, including bacterial, viruses and fungi, and a variety of vaccines and immunotherapies have been developed to treat cancer, and many strategies and adjuvants have been used to enhance their efficacies.

There is ongoing need to develop further treatment and prevention options against infections caused by infectious agents, cancerous cells and immune or inflammatory diseases.

Relevant literature includes WO2016054745 and Gaudet et al.Science348, 1251-1255 (2015).

SUMMARY OF THE INVENTION

The invention provides methods of promoting an immune response and corresponding pharmaceutical compositions.

In an aspect the invention provides a method of promoting an immune response comprising administering to a person in need thereof a composition comprising a 1-ADP-heptose conjugate.

In embodimentsthe heptose is of configuration: L/D-glycero-α/β-L/D-manno/gluco/galacto-heptose.the heptose is of configuration: L/D-glycero-α/β-L/D-manno-heptose.the heptose is of configuration: L/D-glycero-α/β-D-manno-heptose.the heptose is of configuration: L/D-glycero-β-D-manno-heptose.the heptose is of configuration:

L-glycero-β-D-gluco-heptoseL-glycero-β-L-galacto-heptoseD-glycero-β-D-gluco-heptoseD-glycero-β-L-galacto-heptoseL-glycero-α-D-gluco-heptoseL-glycero-α-L-galacto-heptoseD-glycero-α-D-gluco-heptoseD-glycero-α-L-galacto-heptoseL-glycero-β-L-gluco-heptoseL-glycero-β-D-manno-heptoseD-glycero-β-L-gluco-heptoseD-glycero-β-D-manno-heptoseL-glycero-α-L-gluco-heptoseL-glycero-α-D-manno-heptoseD-glycero-α-L-gluco-heptoseD-glycero-α-D-manno-heptoseL-glycero-β-D-galacto-heptoseL-glycero-β-L-manno-heptoseD-glycero-β-D-galacto-heptoseD-glycero-β-L-manno-heptoseL-glycero-α-D-galacto-heptoseL-glycero-α-L-manno-heptose orD-glycero-α-D-galacto-heptoseD-glycero-α-L-manno-heptose;the conjugate is a 1-ADP-heptose-7-phosphate.the method further comprises administering to the person an immunogen, preferably comprising an antigen of a bacterium, virus, parasite or cancer cell.the method further comprises administering to the person an immune checkpoint inhibitor, preferably comprising a therapeutic antibody specific for:

Adenosine A2A receptor (A2AR);

Cluster of Differentiation 276 (CD276; B7-H3);

B and T Lymphocyte Attenuator (BTLA; CD272;

Cytotoxic T lymphocyte-associated protein 4 (CTLA-4);

Indoleamine 2,3-dioxygenase (IDO);

Killer immunoglobulin-like receptor (KIR);

Lymphocyte-activation gene 3 (LAG-3; CD223);

Programmed death protein 1 (PD-1) or programmed death ligand 1 or 2 (PD-L1 or PD-L2);

T cell immunoglobulin mucin 3 (TIM-3); or

V-domain Ig suppressor of T cell activation (VISTA);the checkpoint inhibitor is a therapeutic antibody that is a PD-L1 inhibitor, such as durvalumab, atezolizumab or avelumab; or a CTLA-4 inhibitors such as tremelimumab or tremelimumab;the method further comprises administering to the person the immunogen or immune checkpoint inhibitor, wherein the composition comprises the immunogen or the inhibitor.

In an aspect the invention provides an immune response promoting pharmaceutical composition comprising a 1-ADP-heptose conjugate.

In embodiments:the composition further comprises an immunogen or an immune checkpoint inhibitor.the composition is in unit dosage form.

The invention encompasses all combinations of the particular embodiments recited herein.

