Malaria vaccine development has been confronted with various challenges such as poor immunogenicity of malaria vaccine candidate antigens, which is considered as the main challenge. However, this problem can be managed using appropriate formulations of antigens and adjuvants. Poly(I:C) is a potent Th1 inducer and a human compatible adjuvant capable of stimulating both B- and T-cell immunity. Plasmodium falciparum merozoite surface protein 1 (PfMSP-1) is a promising vaccine candidate for blood stage of malaria that has faced several difficulties in clinical trials, mainly due to improper adjuvants. Therefore, in the current study, poly(I:C), as a potent Th1 inducer adjuvant, was evaluated to improve the immunogenicity of recombinant PfMSP-1, when compared to CFA/IFA, as reference adjuvant. Poly(I:C) produced high level and titers of anti-PfMSP-1 IgG antibodies in which was comparable to CFA/IFA adjuvant. In addition, PfMSP-1 formulated with poly(I:C) elicited a higher ratio of IFN-γ/IL-4 (23.9) and IgG2a/IgG1 (3.77) with more persistent, higher avidity, and titer of IgG2a relative to CFA/IFA, indicating a potent Th1 immune response. Poly(I:C) could also help to induce anti-PfMSP-1 antibodies with higher growth-inhibitory activity than CFA/IFA. Altogether, the results of the current study demonstrated that poly(I:C) is a potent adjuvant that can be appropriate for being used in PfMSP-1-based vaccine formulations.
Abstract:In the present study, effects of lead exposure on licking and yawning behaviour have been studied. The dopaminergic receptor agonist, apomorphine (0.15, 0.25 and 0.5 mgikg), induced dose-dependent licking in rats. The maximum response was obtained with 0.5 mgikg of the apomorphine. Lead acetate (0.05%) exposure significantly increased apomorphine-induced licking. Yawning induced by the D2 dopaminergic agonist, bromocriptine (2, 3, 4, 8 mgikg), and the cholinergic drug, physostigmine (0.1 or 0.3 mg/kg), was significantly decreased by lead acetate (0.05%) exposure. It may be concluded that the behaviour induced by dopaminergic or cholinergic agents can be affected by lead subchronic exposure.The yawning behaviour is a strange and poorly understood response induced in many vertebrate species (Baenninger 1987) Mesolimbic and nigrostriatal dopaminergic pathway may be important in the mediation of locomotor activity and stereotyped behaviours. Locomotion has been related to nucleus accumbens (Jackson et al. 1975), whereas stereotyped behaviours (e.g. head movement, licking and localized sniffing) are more closely associated with the caudatestriatum (Kelly et al. 1975).Lead exposure is still one of the most important health hazards to human, and in particular to children as due to their enhanced sensitivity of developing nervous system, they are more susceptible to lead exposure (Mushak et al. 1989). Lead exposure has been reported in animal experiments (Murayama et al. 1990). It has also been shown that lead is capable of affecting dopamine receptor subtypes (Moresco et al. 1988). Further, lead exposure also has been found to produce functional dopaminergic supersensitivity which involves both the D, and D2 receptor subtypes behaviour, the present study was undertaken to investigate the effects of lead exposure on yawning and licking behaviour induced by dopaminergic and cholinergic agents. Materials and MethodsAnimals. Male albino wistar rats (1 50-250 g; 3 4 months old) were used for all experiments. Prior to use the rats were housed in wire cages in groups of five, with controlled temperature (20+2") and controlled 12 hr light-dark cycle. The animals were allowed ad libitum access to a standard cube diet and water.Lead exposure. Lead was administered according to Moorhouse et al. (1988) with minor modification. In brief, lead was placed in drinking water (acetate form dissolved in distilled water acidified with hydrochloric acid to prevent precipitation of insoluble lead salts). Glucose (5% w/v) was added to each water bottle to improve palatability. Two doses of lead (0.025% and 0.05%) were used in this study and control groups were treated with a corresponding solution of sodium acetate. Similar quantities of acid and glucose were added to the drinking water of the sodium acetate control animals. Animals were divided in 5 groups: the first two groups of animals received lead or sodium acetate for 28 days and licking and yawning behaviour induced by different doses of apomorphine or bromocriptine were tes...
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