Immune responses to HIV-1 polytope vaccine candidate formulated in aqueous and alcoholic extracts of Propolis: Comparable immune responses to Alum and Freund adjuvants
Introduction
The success of a vaccine is derived from its association with the appropriate adjuvant. A suitable adjuvant should increase not only the immunogenicity but also durability of the immune response against the vaccine. In addition, safety of an adjuvant is the most important factor for human vaccines [1]. Adjuvants boost the immune responses [2], may reduce the required amount of antigen or the number of immunization regimens [3]. In general, it is expected that use of suitable adjuvant enhances the efficiency and protection rate of the vaccines. The ideal adjuvant should have some properties such as; inexpensive, biodegradable, biologically inert and boost the cellular and humoral immune responses in addition to having a long life-time [4]. There are many adjuvants with different immunologic functions, but many of them are not suitable for human use due to systemic and local reactions [3,5]. Propolis is a natural resinous material with a characteristic odor that honey bees muster from tree blooms and the exudates of plants. The chemical composition of Propolis varies directly dependent on the variability of the resinous plant materials in different regions [6]. In general, the ethanolic extract of Propolis includes 50% resin and balsams, 30% wax, 10% essential and aromatic oils, 5% pollen grains, some vitamins, mineral elements and enzymes [[7], [8], [9], [10]]. In the last few decades, researchers examined the biological properties and components of Propolis. Now it is evident that Propolis shows immunomodulatory effect [[11], [12], [13], [14]] without toxicity effect in mouse model [7,15,16]. It has been shown that aqueous or alcohol extracts have immunomodulatory effect and are able to improve immune responses against various immunogens [[17], [18], [19], [20], [21]]. Considering the previous studies, it seems that Propolis components (aqueous or alcoholic extracts) have adjuvant activity. For this purpose in the present study adjuvant properties of aqueous and alcoholic extracts of Propolis in a multi-epitope HIV-1 vaccine is evaluated and compared with Alum and Freund's as golden standard adjuvants. Herein, all aspects of humoral and cellular immune responses were assessed in the experimental groups.
Section snippets
Preparation of alcoholic and aqueous extracts of Propolis
In the present study, alcoholic and aqueous extracts of Propolis are prepared by routine protocols reported by researchers previously with some modifications [[22], [23], [24]]. Ninety grams crude Propolis was grounded with homogenizer, macerated with 300 ml ethanol (95–96%) for 11 days, and occasionally agitated for 10 min every day. Afterward, it was centrifuged for 20 min at 3000g and clear supernatant filtered and lyophilized for future use. In addition, Ninety grams crude Propolis was
Lymphocyte proliferation
The result of lymphocyte proliferation showed a significant increase in all experimental vaccine groups as compared with control groups (P ≤ 0.014). As shown in Fig. 1, immunization with vaccine candidates formulated in aqueous and alcoholic extracts does not show significant differences in comparison to Alum (P ≥ 0.144) and Freund's (P ≥ 0.522) adjuvanted groups. In addition, there wasn't significant difference between aqueous and alcoholic extracts adjuvanted vaccines (P = 0.522). (Fig. 1).
ELISA of IL-4 and IFN-γ cytokines
Discussion
Natural products are fertile sources for new medicines. The use of these products as an immunomodulator will be very useful. Prior studies have noted the importance of Propolis as an adjuvant and have demonstrated Propolis' immunomodulatory activity [29]. In the present study, adjuvant activity of aqueous and alcoholic extracts of Propolis in HIV-1 multi-epitope vaccine model is assessed and also compared with vaccine formulated in Alum and Freund's as golden standard adjuvants. Lymphocyte
Financial disclosure
There is no conflict of interest.
Declaration of competing interest
The authors of this research article have no financial conflict of interest statement.
Acknowledgments
This work was supported in part by a grant from Pasteur Institute of Iran, Tehran, Iran. We thank Dr. Ali Farrokhi from University of British Columbia for manuscript edition.
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