Potential Efficiency of Various Adjuvants in Combination with Recombinant Protective Antigen of Anthrax Cause

Автор: N.I. Mikshis, A.P. Semakova, P.Yu. Popova, O.M. Kudriavtseva, T.N. Kashtanova, L.V. Novikova, A.V.Stepanov, and S.A. Bugorkova

Страница: 36-42

Potential Efficiency of Various Adjuvants in Combination with Recombinant Protective Antigen of Anthrax Cause

Russian Journal of Biotechnology, 2014, N 6, P. 36-42

UDC 616.98:579.852.11

Section:  “Biologicals Technology”

N.I. Mikshis ^*,  A.P. Semakova,  P.Yu. Popova,  O.M. Kudriavtseva,  T.N. Kashtanova,  L.V. Novikova,  A.V.Stepanov,  and  S.A. Bugorkova

The Russian Research Antiplague Institute Microbe,  410005, Saratov Russia

e-mail:  rusrapi@microbe.ru

The efficacies of the aluminum hydroxide gel, monophosphorylated lipid (MPL), and CpG 2006 as adjuvants of various classes in preparations containing rPA have been compared. BALB/c mice were immunized subcutaneously with a single or double dose of the recombinant protective antigen (rPA) combined with one of the adjuvants. The innate immunity structure activation was observed through the changes in the expression of Toll-like receptors (TLR) genes. The protective activity of the preparations was evaluated on the basis of the LD₅₀ index of the infecting test strain. The morphometric parameters were assessed using Guinea pigs. It was determined that the combination of rPA with MPL or rPA with CpG 2006 was most effective in respect of inducing TLR. The increase in TLR2, TLR 4, TLR 6, and TLR 9 contents on the cells of immuno-competent organs in mice immunized with rPA with MPL or rPA with CpG 2006 was observed. The pathomorphological investigation detected a practical absence of visible changes in organs and tissues of Guinea pigs 7 days after the twofold immunization with rPA + CpG 2006 or a combination of aluminum hydroxide gel and CpG 2006. The minimal disorders in histological samples were within the tolerability limits and as a whole, reflected a stress reaction to the introduction of the preparation. It was demonstrated that the alhydrogel-adsorbed rPA had lower protective activity as compared to the other preparations. The expression of TLR2, TLR 4, TLR 6, and TLR 9 genes in the mice immunized with the preparation was feebly detected, whereas, on the contrary, the changes in parenchymal organs of Guinea pigs were manifested to a greater extent. Consequently, the combinations of rPA with either of the new generation adjuvant, CpG 2006 or MPL, were accepted as promising.

Key words:  adjuvants,  anthrax,  antianthrax vaccine,  Bacillus anthracis,  recombinant protective antigen.

31.03.2015, 1496 просмотров.