Early immune response in mice immunized with a semi-split inactivated vaccine against SARS-CoV-2 containing S protein-free particles and subunit S protein

The development of a vaccine against COVID-19 is a hot topic for many research laboratories all over the world. Our aim was to design a semi-split inactivated vaccine offering a wide range of multi-epitope determinants important for the immune system including not only the spike (S) protein but also the envelope, membrane and nucleocapsid proteins. We designed a semi-split vaccine prototype consisting of S protein-depleted viral particles and free S protein. Next, we investigated its immunogenic potential in BALB/c mice. The animals were immunized intradermally or intramuscularly with the dose adjusted with buffer or addition of aluminum hydroxide, respectively. The antibody response was evaluated by plasma analysis at 7 days after the first or second dose. The immune cell response was studied by flow cytometry analysis of splenocytes. The data showed a very early onset of both S protein-specific antibodies and virus-neutralizing antibodies at 90% inhibition regardless of the route of vaccine administration. However, significantly higher levels of neutralizing antibodies were detected in the intradermally (geometric mean titer - GMT of 7.8 ± 1.4) than in the intramuscularly immunized mice (GMT of 6.2 ± 1.5). In accordance with this, stimulation of cellular immunity by the semi-split vaccine was suggested by elevated levels of B and T lymphocyte subpopulations in the murine spleens. These responses were more predominant in the intradermally immunized mice compared with the intramuscular route of administration. The upward trend in the levels of plasmablasts, memory B cells, Th1 and Th2 lymphocytes, including follicular helper T cells, was confirmed even in mice receiving the vaccine intradermally at a dose of 0.5 μg.We demonstrated that the semi-split vaccine is capable of eliciting both humoral and cellular immunity early after vaccination. Our prototype thus represents a promising step toward the development of an efficient anti-COVID-19 vaccine for human use.

THE EFFECT OF SUBACUTE INTOXICATION WITH ETHYLENE CHLOROHYDRIN ON IMMUNE RESPONSES, TH1 AND TH2 LYMPHOCYTE FUNCTION AND CYTOKINE LEVELS IN RATS BLOOD

In experiments on outbred albino rats, it was established that subacute intoxication with ethylene chlorohydrin (0.2 LD50 daily for 4 days) causes a decrease in Th1 and Th2 lymphocytes function to the same extent, diminishes parameters of humoral and cellular immune responses and the content of immunoregulatory cytokines IFN- , IL-2, IL-4 in blood, increases concentrations of pro-inflammatory cytokine IL-6 and anti-inflammatory cytokine IL-10.

The effect of in vivo exposure to zearalenone on cytokine secretion by Th1 and Th2 lymphocytes in porcine Peyer’s patches after in vitro stimulation with LPS

Most research studies investigating the estrogenic effects of zearalenone (ZEN) focus on the mycotoxin’s effect on the reproductive system. Since estrogen receptors are present on various types of immunocompetent cells, ZEN can also modify diverse immune functions. This study analyzed immunocompetent cells isolated from Peyer’s patches in the ileum of pigs administered ZEN in the estimated daily dose of 8 μg kg-1 BW (equivalent of 100 μg kg-1 feed per day-1). The objective of the study was to determine whether long-term exposure to low ZEN doses below the NOEL threshold leads to changes in the percentages of lymphocyte subpopulations and cytokine secretion by Th1 (IL-2, IFN-γ) and Th2 (IL-4 and IL-10) lymphocytes in Peyer’s patches of the ileum after in vitro stimulation with lipopolysaccharides (LPS). Immunocompetent cells isolated from Payer’s patches on experimental days 0, 14, 28 and 42 were cultured in vitro and stimulated with LPS. The presence of IL-2, IFN-γ, IL-4 and IL-10 in culture media was determined by the ELISA method. The results of the study indicate that ZEN inhibits IL-2 and IFN-γ secretion and stimulates IL-4 and IL-10 production by Th1 and Th2 lymphocytes by shifting the Th1/Th2 balance towards the humoral immune response. The above can promote allergic responses, as demonstrated by the increase in the size of B1 cell populations producing more autoantibodies. ZEN can also lower resistance to viruses and tumors by inhibiting the proliferation of NK cells and IFN-γ secretion.