الفهرس 
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Abstract
Rift valley fever virus vaccine prepared in Egypt during 1981. The currently prepared vaccine is formalin inactivated one, prepared in Veterinary Serum and Vaccine Research Institute for sera and veterinary vaccines and the Egyptian Organization for biological products and vaccines (VACSERA), despite the used strains are of different origins; ZH(501) and M/S/258) respectively. The side effects of formaldehyde are well known and the risks are many. The use of new inactivants must be considered for higher safety measures and better antigenicity. The choose of cheap and safer inactivants are of the parameters for improving the quality of vaccines industry. Ascorbic acid proved to has antiviral activity to some viruses such as Polio, rabies, cytomegalovirus viruses, in addition its effect on the released interferon level; accordingly it was interestingly tried for the inactivation of Rift Valley fever virus as an economic matter of importance.
Efficacy of ascorbic acid and Beta propiolactone as inactivants were monitored and the inactivation kinetics was evaluated compared with formalin as a traditional inactivating agent. The depletion rate of ascorbic acid was 0.95 log (10) TCID50/ hr and 1.16 log (10) MICLD50 / hr when virus infectivity titre was evaluated in cell culture and mice repetitively, in the mean time no residual live virus could be detected 24 hrs post treatment. Data recorded revealed that RVFV was completely inactivated within 2 hrs post beta-propiolactone treatment recording a mean depletion of virus infectivity titer in the order of 1.2 log (10) TCID50/ 15 min (= 4.8 log (10)/ hrs) and 1.8 log (10) MIPLD50/ 15 min (= 7.2 log (10)/ hrs). The effective dose that can protect 50 % of immunized mice (ED50) found to be contained in 0.006 ml of BPL inactivated RVFV vaccine while it was contained 0.011 ml of formalin inactivated vaccine and 0.0024 ml in ascorbic acid inactivated vaccine.
Mice humoral immune response developed against ascorbic acid, beta-propiolactone and formalin inactivated RVFV vaccines was monitored using ELISA for detection of antibody level, and the optical density was representing to the Ab level. Ab level post immunization with Formalin – CAP, BPL-CAP and A.A-CAP adsorbed vaccine models showed the highest Ab level compared to that elicited post immunization with (formalin , formalin – Alum , BPL, BPL-Alum, A.A and A.A- Alum adsorbed vaccines), and the peak was reached on the 5th week post-immunization.
Cellular immune response could be monitored through evaluation of IFN-γ as example of Th1. Sera collected at time intervals showed differential profile of secreted IFN-γ. All vaccine candidates showed a detectable amount of IFN-γ secreted in sera on 7th day. Also, the maximum level of IFN-γ detected on 28th days post vaccination mice groups with AA-CAP, BPL-Alum, F-CAP adsorbed vaccines respectively.
Subcutaneous administration is the most appropriate route for delivering RVF antigen because the antigen can drain directly from the injection site to lymph nodes where immunocompetent cells reside. Nanoparticles, having a size ranging from 1-1,000 nm, are considered as the most promising adjuvant for subcutaneous immunization. Calcium phosphate and Aluminium phosphate Nanoparticles as adjuvants are commercially available that can potentiate the immune response to antigens. A transmission electron photomicrography of Ca-ph and Al-ph adjuvants revealed a spherical particles having particle size of approximately 96 nm and 208 nm respectively. Calcium adjuvant is claimed to be a normal constituent of the body that is well tolerated and readily resorbed. While Aluminium adjuvant in vaccines was hypothesized as one factor leading to increased allergic diseases. Effects of calcium phosphate and aluminium phosphate adjuvants were examined for histopathological changes. Severity of soft tissue irritation due to calcium phosphate suspension was similar to that due to Al-suspension except for the duration of the inflammatory reactions. Calcium phosphate suspension induced tissue reactions completely ceased by the 4th week, while aluminium phosphate suspension induced reactions were seen up to the 8th week or sometime longer.