Poly[di(carboxylatophenoxy)phosphazene] (PCPP) is a potent immunoadjuvant for an influenza vaccine.

The adjuvant activity of poly[di(carboxylatophenoxy)phosphazene] (PCPP) on the immunogenicity of formalin-inactivated influenza virions and commercial trivalent influenza vaccine was studied. Regardless of which antigen preparation is used, the addition of 100 micrograms PCPP enhances the HAI antibody response 10-fold over the levels elicited by the vaccine alone. Similarly, PCPP enhanced the IgM, IgG, and IgG1 ELISA antibody titers to influenza antigens at least 10-fold higher than the vaccine alone. In contrast, the IgG2a isotype titers were only enhanced about 2-fold. Immunization of aged mice (22 months old) with trivalent influenza vaccine alone did not sero-convert these mice as measured by HAI or ELISA whereas significant sero-conversion was achieved when mice were immunized with PCPP-formulated trivalent vaccine. The adjuvant activity of PCPP was shown to not be due to a site of injection depot effect. PCPP adjuvanticity was positively correlated to the molecular weight of the polymer.

Interleukin-11 expression in donor bone marrow cells improves hematological reconstitution in lethally irradiated recipient mice.

Lethally irradiated mice were transplanted with syngeneic bone marrow cells infected with a recombinant retrovirus vector containing the human interleukin-11 (hIL-11) cDNA under the control of the human cytomegalovirus (CMV) immediate early promoter. The hIL-11 RNA transcript from the vector was detected in the spleen and bone marrow of the recipient mice, and hIL-11 protein accumulated in their serum. The hematological reconstitution of these mice was compared with recipient mice rescued with bone marrow infected with the parental retrovirus vector not containing the hIL-11 cDNA. The hIL-11-expressing mice had an accelerated recovery of circulating platelets and red and white blood cells. Three months after the transplantation, bone marrow was harvested from the mice and used to rescue other lethally irradiated recipients. The hIL-11 mRNA and protein were also detected in these secondary recipients, and the mice showed improved hematological reconstitution relative to a control group. No abnormal cell proliferation or other histopathology was observed in the hIL-11-expressing mice.

Recombinant human interleukin-11 stimulates megakaryocytopoiesis and increases peripheral platelets in normal and splenectomized mice.

The effects of recombinant human interleukin-11 (rhIL-11) on in vivo mouse megakaryocytopoeisis were examined. Normal C57Bl/6 mice and splenectomized C57Bl/6 mice were treated for 7 days with 150 micrograms/kg rhIL-11 administered subcutaneously. In normal mice, peripheral platelet counts were elevated compared with vehicle-treated controls after 3 days of rhIL-11 treatment and remained elevated until day 10. Splenectomized mice treated with rhIL-11 showed elevated peripheral platelet counts that were similar in magnitude to normal rhIL-11-treated mice. However, on day 10 the platelet counts in rhIL-11-treated, splenectomized mice were no longer elevated. Analysis of bone marrow megakaryocyte ploidy by two-color flow cytometry showed an increase, relative to controls, in the percentage of 32N megakaryocytes in both normal and splenectomized animals treated with rhIL-11. In normal mice, the number of spleen megakaryocyte colony-forming cells (MEG-CFC) were increased twofold to threefold relative to controls after 3 and 7 days of rhIL-11 treatment, whereas the number of bone marrow MEG-CFC were increased only on day 7. The number of MEG-CFC in the bone marrow of rhIL-11-treated, splenectomized mice was increased twofold compared with controls on both days 3 and 7 of the study. These data show that in vivo treatment of normal or splenectomized mice with rhIL-11 increased megakaryocyte progenitors, stimulated endoreplication of bone marrow megakaryocytes, and increased peripheral platelet counts. In addition, results in splenectomized mice showed that splenic hematopoiesis was not essential for the observed increases in peripheral platelets in response to rhIL-11 administration.