ODFs as carriers for antiviral vaccines The Center for Disease Control and Prevention defines vaccines as ‘A product that stimulates a person’s immune system to produce immunity to a specific disease, protecting the person from that disease. Vaccines are usually administered through needle injections, but can also be administered by mouth or sprayed into the nose’ [102]. Vaccination is considered as one of the most effective ways of preventing cause of a disease [103]. At present, there are several companies, academic institutes that are actively working to develop a vaccine against COVID-19. Vaccines that are currently under development are provided in Table 5. Table 5. Antiviral vaccines in pipeline for treating COVID-19. Name of the player Details of antiviral vaccines under development Ref. Migal Galilee Research Institute, Israel Developing an oral (mucosal) vaccine, wherein the viral antigen is delivered via mucosa tissues by self-activated endocytosis [104] Entos Pharmaceuticals Fusogenix – DNA vaccine is being developed based on its patent protected platform, proteo-lipid vehicle (PLV). It uses a new mechanism for delivering genetic material into the cells [105,106] Vaxart Inc Oral recombinant vaccine in tablet formulation using its VAAST platform. It has protected its vaccine tablet formulation by US patent applications [107–109] University of Oxford – Jenner Institute ChAD0X1 nCoV-19 – prepared from cold virus (weakened) – initiated Phase III trials [110] Altimmune AdCOVID – vaccine delivered via intranasal route platform technologies NasoVAX and NasoShield [111,112] Medicago Developing a vaccine and also an antibody. It was successful in producing virus like particles of coronavirus. It is developing antibodies in collaboration with Laval University [113] Inovio Pharmaceuticals INO-4800 – vaccine that is developed in collaboration with Beijing Advaccinee Biotechnology Company. It is proposing to deliver the vaccine using the device called as CELLECTRA® which works by creating a pulse for transferring the plasmids across the cell. It is also developing INO 4700 in collaboration with GeneOne Life Sciences company [114] Moderna mRN 1273 – recently received fast track designation from USFDA. It vaccine basically targets spike protein of corona virus [115] Tonix Pharmaceuticals TNX-1800 – developed based on its horsepox virus vaccine platform. It has filed a provisional patent application with USPTO [116] Clover Biopharmaceuticals Subunit vaccine developed using trimeric spike protein developed using its patented technology [117] Novavax, Inc Middle East Respiratory Syndrome (MERS) vaccine was developed using recombinant nanoparticle based vaccine technology. The vaccine showed positive results in inhibiting the virus when administered along with its patented adjuvant formulations [118–121] Predictive oncology (PO) Introduced artificial intelligence for development of a vaccine using Inventa Biotech’s HSCTM technology which deals with chromatographic system of high throughput screening. In addition, PO is also developing a new vaccine based on nanoparticle (NSP-10: non specific protein) platform technology developed by Dr. Daniel Carter [122] Primarily, vaccines pose extreme challenges vis-a-vis its handling, (cold) storage and shipping, all expensive propositions. For instance, one of the studies reported that 38 billion USD would be spent on transportation and administration of 18 vaccines in 94 countries [123,124]. Therefore, there is a need for alternate dosage forms that can help reducing the cost. For instance, Vaxart Inc is developing recombinant vaccine for COVID-19 in tablet formulation using its patent protected technology called VAAST [107–109]. RP Scherer Technologies LLC is also developing a tablet formulation (fast dissolving) for influenza vaccine with starch as immune stimulating agent [125]. Tablets are highly traditional and conventional dosage forms that are difficult to administer to patients who have dysphagia or Parkinson’s disease and are extremely difficult to administer to pediatrics and geriatrics. Therefore, ODFs remain as an alternate choice of administration as they do not need water to consume. Most importantly, they are easy to transport from one place to another. Israel’s Migal Galilee Research Institute is actively developing a vaccine that is administered via oromucosal route [104]. Some of the vaccine preparations that are successfully formulated as ODFs are provided in Table 6. Table 6. Antiviral vaccines that are formulated as ODFs. Name of the player Name of vaccine formulated as ODFs Polymer Plasticizer Method employed Key highlight(s) Ref. The Johns Hopkins University Several live-attenuated viruses were proposed, including the corona virus. Provided methodology to prepare rotavirus vaccine Eudragit Polyethylene glycol (PEG) and polyvinyl alcohol (PVA) Double emulsion solvent evaporation Prepared as monolayered or bi layered ODFs [126] Brian Pulliam (single applicant and inventor) Rotavirus vaccine along with an antacid namely magnesium hydroxide or aluminum hydroxide nanoparticles for digestion purpose Polyvinyl pyrrolidone +  hydroxypropyl cellulose (HPC) PEG Solvent casting method (SCM) Antacid successfully combined with a vaccine in layered fashion [22] Nitto Denko Corporation Cancer vaccine comprising WT1 peptide or Db126 along with a promoter namely lipopolysaccharide or quercetin or ioxoprofen Mannitol, PEG, and HPC PEG, mannitol SCM Composition successfully induces cellular immunity in cancer patients [127] Nasir Uddin from Larkin University Gonorrhoea microparticulate vaccine a a SCM Microparticulate vaccine particles were obtained by spray dryingBilayered ODFs can be prepared, outer layer acts as protection layer [128] Aridis Pharmaceuticals Rotavirus vaccine a a a Patent protected vaccine stabilization technology and plasticized glass stabilization technology were employed in preparing the vaccine film [129–131] a Nothing found. Administration of vaccines using fast dissolving buccal films is the most optimized form of administration as it has plethora of advantages when compared with parenteral route of administration [132]. Research suggests that vaccines administered via oral route are as good as or even better than those that are administered via parenteral route. For instance, Bajrovic et al. demonstrated that oral administration (sublingual and buccal routes) of influenza virus vaccine as a thin film formulation has shown good or better results than the vaccine that is administered via intramuscular route [133]. From Table 6, it is evident that ODFs comprising vaccines can be prepared as mono or bilayered using the most popular solvent casting method. Tian et al. prepared influenza virus vaccine by using trehalose and pullulan to maintain the stability and antigenicity of the vaccine. They also employed hypromellose that further helped in enhancing the stability of the film [134]. ODFs remain an excellent option for delivery of vaccines to subjects across all the age groups. They are easily portable and maintain stability of the vaccine during transportation till it reaches to the subject for consumption. All these strongly suggest that ODFs are cost-effective carriers and easy to consume dosage forms.