Investigation On Defective Interfering Particles Of Paramyxovirus, Tianjin Strain Used As A New Biologic Adjuvant

Objective The weak immunogenicity of novel vaccines like genetic engineering polypeptide or subunit vaccines and synthetic peptide vaccines cause the broadly applying of adjuvants, which are extended to using in other territories like adjunctive anti-infection or anti-tumor therapy. It is critical for the development of vaccine to find ideal adjuvents. The frequent adjuvents include alum salts, emulsions, bacterial derivatives, nucleic acids and the analogues, cytokines, ISCOMs, propolis, liposome and so on. Defective interfering(DI) particles are virus with subgenome, which are generated from the wrong replication. The property of DI particles makes their genome carrying some information which standard virus doesn’t have. Some recent researches showed the DI particles of Sendai virus(SeV) could potently help to stimulating the mutation of dendritic cells(DCs). Paramyxovirus, Tianjin Strain was isolated from the lungs of cotton-eared marmosets which were burst out to catch the acute upper respiratory infection in1999. It was identified being a member of the Respirovirus of Paramyxovirus family, and a new genotype of SeV which has the nearest genetic relationship with it. So we do a prime study to see whether the DI particles of Paramyxovirus, Tianjin Strain can be used as a novel adjuvant.Methods The Paramyxovirus, Tianjin Strain was obtained by cultivation in the chick embryo. The DI particles of Paramyxovirus, Tianjin Strain were obtained through ultracentrifugation purification and sucrose density gradient purification and identified by showing under the electron microscope, observing the CPE after DI particles being inoculated in rat neurospongioma cell, C6strain and detecting the HA titers of allantoic fluid collected after cultivating DI particles in the chick embryo. The DI particles of Paramyxovirus, Tianjin Strain were balanced mixed with the inactivated poliovirus (PV) vaccine. ICR mice about4weeks old were administered subcutaneously with the mixture, besides we set groups of inactivated PV vaccine containing Al(OH)3as an adjuvant, inactivated PV vaccine of which the dose was doubled without any adjuvant, and normal saline as control. The survival of the mice was observed. Sera were collected in the14th day after immunization, and the specific antibodies of PV were detected. T/B lymphocyte stimulation indexes (SI) were counted through the lymphocyte proliferation tests. The quantities of IFN-y/IL-4produced by the splenocytes which were stimulated again by PV antigen were detected.Results It was showed that the formulations isolated by purification were DI particles which were different from the standard virus. The level of sera specific antibodies in the group of inactivated PV vaccine combining with DI particles of Paramyxovirus, Tianjin Strain was higher than the negative control group but lower than the Al(OH)3group, The T lymphocyte SI and the quantity of IFN-γ in the group of DI particles were more than other groups, The B lymphocyte SI and the quantity of IL-4in the group of DI particles were no more than other groups.Conclusion The DI particles of Paramyxovirus, Tianjin Strain could enhance the immune response of inactivated poliovirus, especially the cellullar immunologic response of Thl type. This study showed that the DI particles of Paramyxovirus, Tianjin Strain have adjuvant activity, so they have the potential capability to develop a new candidate adjuvant.