Spike protein, 8. proteins8Phase I/IIInjection Open in a separate window Abbreviations: 1. Tool like receptor 7/8, 2. Inactivated hepatitis A virus, 3. Apical membrane antigen 1, 4. Circumsporozoite protein, 5. Plasmodium falciparum cysteine-rich protective antigens, 6. Three co-stimulatory molecules, 7. Spike protein, 8. Good manufacturing practice. 4.1. Influenza Conventional influenza vaccine platforms Aesculin (Esculin) protect the population against some highly pathogenic strains; however, adequate information elucidates that these products do not have enough protection against the future pandemic. Therefore, new vaccine technology development is essential to produce community immunity. Virosome based influenza vaccines are a novel FDA approved technology that mitigates viral morbidity and mortality rate [63]. Inflexal?V is the trivalent influenza virus virosome vaccine in which the formulation contains an inactivated form of two virus strains and one B virus strain with the influenza virus’s specific antigen HA and NA subunits [52]. Like other virosomes preparation techniques, in influenza virosome development, the optimized amount of detergents has solubilized influenza viruses, their nucleocapsid was removed; consequently, IRIV naturally formed in the presence of viral lipids and glycoproteins. Phospholipids (PL), especially phosphatidylcholines (PC), attain in virosome reconstitutions. PC assigned 70% of virus lipid content that 30% achieved by envelope phospholipids originating XCL1 from the influenza virus to provide NA and HA glycoproteins [64]. In Fig. 5 , we showed the schematic illustration of influenza reconstituted virosome. Open in a separate window Fig. 5 Schematic design of influenza virosome. The NA has a tetramer structure consisting of four similar monomers, spherical subunits hydrophobically anchored into IRIV phospholipid membrane by a central stalk. NA function significantly affects the viral virulence and improves the action of virosomes. em N /em -acetylneuraminic acid (sialic acid) from bound sugar residues reduces the host’s mucus viscosity and facilitates the release of progeny viruses at the budding stage and access to epithelial cells. The HA epitopes comprised of HA1 and HA2 subunit played a crucial role in the virus-endosomal fusion and provoked cellular immunity. Besides, HA incorporation into the virosome membrane is confined to virosome-virosome fusion [65]. First, Inflexal?V has been produced by the Swiss Serum and Vaccine Institute, Berne, Switzerland, since 1997, which is now commercialized in over 20 countries worldwide by different trade names as Isiflu? V in Italy and as Viroflu? in the United Kingdom. Up to date, 18 clinical trials have been done on more than 2500 healthy volunteers reporting the safety and efficacy of Inflexal?V. This vaccine presented outstanding tolerability in all age groups and exceeded 10 million vaccine doses have been administered [66]. Inflexal?V eliminated the conventional influenza vaccine limitations, contained no thiomersal or formaldehyde in formulations, and reduced allergic Aesculin (Esculin) reactions by the lowest OVA content. Producing stabilized Aesculin (Esculin) vaccine formulation under varying storage conditions significantly improved vaccination safety and decreased preservation cost. Inflexal?V has been shown to maintain high levels of HA content for 24 months [67]. As WHO recommended, and due to the high mutation rate of influenza viruses that changes the amino acid composition of the HA and NA antigens and the mean diameter of virosome particle size, they will notify each season’s new influenza strains [46,[68], [69], [70]]. 4.2. Hepatitis A Hepatitis A is a life-threatening disease caused by Hepatovirus A (HAV). HAV is an RNA virus surrounded by cubic or icosahedral capsid proteins of 27C32 nm diameter. This virus is stable at low pH, temperature and inactivated in heat above 85 c. Vaccination in the high-risk population against HAV could provide universal immunization. Several types of vaccines developed for HAV as Havrix?, Vaqta?, Avaxim?, and Epaxel? that Epaxel? are the only aluminum-free product. Fig. 6 presented a schematic feature of the virosome used in Epaxel formulation. Epaxel? developed by virosome is decorated with inactivated HAV, while aluminum hydroxide adjuvant was used as the substrate for attachment of HAV inactivated virus in other vaccines. Aluminum hydroxide adjuvant declined local inflammatory responses. This potent viral vaccine provides more rapid immune responses with a higher seroconversion rate at day 14,.