Low-dose influenza vaccine Grippol Quadrivalent with adjuvant Polyoxidonium induces a T helper-2 mediated humoral immune response and increases NK cell activity.

The influenza vaccine Grippol® Quadrivalent (GQ) is a new vaccine, containing the adjuvant Polyoxidonium® and recombinant hemagglutinins from 4 strains of the influenza virus in amount of 5-6 µg of each hemagglutinin per human dose. These doses of antigens are about 3 times less than the standard dose recommended by WHO. We sought to characterize the immune response to the GQ vaccine and to determine the contribution of the adjuvant in this response. BALB/c mice were vaccinated with GQ or with adjuvant-free antigen mixtures (AGs). Then, the antibody response, the number of memory T cells in the spleen, and the functional properties of splenocytes were determined. The vaccine GQ has been shown to induce antibodies to all 4 influenza hemagglutinins. The vaccination with GQ caused a strong increase in the AG-induced proliferation and production of Th2 cytokines ex vivo. These effects were equal to effect achieved by standard dose of antigens. Vaccination also caused the accumulation of CD4+ large lymphocytes with the phenotype of central and effector memory T cells in the spleen. The GQ vaccine enhanced the cytolytic activity of natural killer (NK) cells, whereas the adjuvant-free mixture of AGs in lowered and standard doses did not affect NK activity. We did not find a noticeable response of Th1 and CD8+ T cells to vaccination. In vitro, the GQ vaccine stimulated the maturation of human monocyte-derived dendritic cells (DCs) enhancing the expression of HLA-DR, CD80, CD83, CD86 and ICOSL molecules. Polyoxidonium without AGs also induced expression of ICOSL, which plays an important role in T-dependent humoral immune response. In summary, the low-dose influenza vaccine GQ with Polyoxidonium adjuvant is immunogenic, induces a Th2-polarized T-cell response and CD4+ memory T cells maturation, activates the production of antibodies to influenza hemagglutinins, and increases the activity of NK cells.

Effect of cytotrophoblast cells on T lymphocyte surface antigen expression in cultures of peripheral blood mononuclear cells from pregnant woman and umbilical cord blood mononuclear cells from newborns.

We studied the action of cytotrophoblast cells (CTC) on the expression of T lymphocyte membrane markers in the cultures of newborn cord blood mononuclear cells (CBMC) and peripheral blood mononuclear cells (PBMC) of a pregnant woman. The CTC were separated from the placental chorion at ten weeks of gestation time. In this abstract we show that the CTC and the CTC culture supernatant (SN) increase the number of HLA DR(+)CD7(+) T cells activated by anti-CD3 mAbs, both in PBMC and CBMC cultures. CTC increased the number of transferrine receptor CD71(+) lymphocytes without anti-CD3 activation in CBMC cultures. The increase in the blood mononuclear cell proliferation did not come with an increase of HLA DR and CD71 expression induced by CTC or SN. Moreover, SN caused the suppression of activated T lymphocyte proliferation. We found no signs of any influence of CTC and SN on the expression of CD25 in CD4(+) and CD8(+) subpopulations of T lymphocytes, either activated or non-activated by anti-CD3. The data regarding the CTC- and SN-induced HLA DR expression in vitro suggest that the previously determined high level of HLA DR(+) T cells in the placenta and decidua in pregnant women might have been the result the activity of the trophoblast cells and their soluble products on the lymphocytes of that area.

The Cord Blood T cell Proliferation and Apoptosis: Influence of Interleukin-2, -4, -7 and Dexametasone.

We have shown that the severity of newborns' clinical condition is accompanied by two independent deviations in functional properties of T cells: week proliferative response to activation through CD3 molecule and high sensitivity to apoptosis. Studies of effects exerted by recombinant interleukins and dexamethasone upon cord blood mononuclear cell (CBMC) apoptosis proves that the IL-2, -4 and -7 deficiency is common to enhance apoptosis in CBMC cultures of newborn infants. However, interleukin deficiency is not the sole cause of high level of CBMC apoptosis, and some other factors are required, which may determine the cell sensitivity towards apoptosis. The weakness of proliferative response of T cells to activation seems to be determined rather by the effect of suppressive factors, production of which can be blocked by dexamethasone, than by the death of activated cells in apoptosis.