Most current vaccines are administered through needles and syringes. Injections are given either subcutaneously (below the skin), intradermally (into the skin) or intramuscularly (into the muscle). However, the use of needles presents several disadvantages. For example, needle fears are a documented barrier to immunization in children and adults. It’s not surprising, then, that much research is being dedicated to the identification of effective needle-free technologies for vaccine administration. Among the many technologies currently in development, the MucoJet delivery system has very recently shown promising results in animal studies.
In a study published yesterday (March 8, 2017) in the journal Science Translational Medicine, a group pf researchers showed the efficacy—in rabbits—of the Mucojet, a needle-free delivery device. According to the researchers, “the Mucojet uses a self-contained gas-generating chemical reaction within its two-compartment plastic housing to produce a high-pressure liquid jet of vaccine.” The researchers showed that the vaccine jet ejected from the MucoJet device is capable of penetrating the buccal mucosal layer. For the immunization experiments in rabbits, the MucoJet was placed against the cheek inside the oral cavity. The test vaccine consisted of ovalbumin, a protein frequently utilized in preliminary immunization studies. The researchers found that the rabbits produced anti-ovalbumin antibodies up to 6 weeks after vaccination.
Although the buccal region is rich in immune cells, it is not frequently used as a site for injecting vaccines. This is because currently available technologies do not lead to the efficient penetration of the thick mucosal layer in this part of the oral cavity, as for example in the case of the oral spray often used for influenza vaccination.
MucoJet includes two plastic compartments, which are 3D-printed from a biocompatible and water-resistant plastic resin. The exterior compartment holds water. The interior compartment is composed of two reservoirs separated by a porous plastic membrane and a movable piston. One reservoir contains a chamber of vaccine solution with a piston at one end and a sealed delivery nozzle at the other end. The other reservoir contains a dry chemical propellant consisting of citric acid and sodium bicarbonate).
To administer the MucoJet, a patient clicks together the interior and exterior compartments, causing a chemical reaction that generates carbon dioxide gas. The gas increases the pressure in the propellant chamber, causing the piston to move. When the pressure in the propellant chamber is high enough, the force on the piston breaks the nozzle seal of the vaccine reservoir. The vaccine solution is then ejected from the MucoJet nozzle, penetrates the mucosal layer of the buccal tissue, and delivers the vaccine to the underlying antigen-presenting cells.
Kiana Aran, senior author of the study, said in a press release that the jet is similar in pressure to a water pick that dentists use. She added: “The pressure is very focused, the diameter of the jet is very small, so that’s how it penetrates the mucosal layer. Imagine if we could put the Mucojet in a lollipop and have kids hold it in their cheek. They wouldn’t have to go to a clinic to get a vaccine.”
Needle free vaccines are interesting and innovative. However, I am skeptical of the mode of administration of the MucoJet. The idea of self-administering vaccines is great but I do not know how comfortable parents will be with their children being given pressurized pills. After seeing the size of the pill, I think it could pose a choking hazard not only to children but adults as well. In a recent study by Gala et al., they developed an orally disintegrating film (ODF) carrying measles vaccine microparticles that successfully traveled through the buccal mucosa of pigs. It was determined that after the film was dissolved, the vaccine was taken up by antigen presenting cells and elicited an immune response. This method resulted in higher antigen presenting to MHCI, MHCII, CD40, and CD80. I think this is a more consumer friendly way to administer needle free vaccines. I believe that people will be more comfortable with handling a vaccine that dissolves into the buccal mucosa rather than forcing into it.
I personally believe needle free vaccinations is a very convenient and painless way to administer vaccines to people. Like many others, I hated leaving the doctor’s office in pain from a needle and this technology would resolve that issue. According to an article, needle free injection technology (NFIT) products have a variety of benefits for patients and healthcare providers. One benefit for healthcare providers is that NFIT products can be easily sterilized than the average needle or syringe injection that is commonly used today (1). It has also been found that the shelf life of these products are longer. For patients, this type of vaccine administration provides convenience because NFIT products are simple, do not need to have expert supervision, and can be easily disposed at home (1). NFIT is not just limited to the muscular and dermal tissue areas like needle injections, it can be administered in many different areas of the body such as adipose tissues, mucosal tissues, and dermal tissues (1). As stated in the article above, the biggest advantage of this type of vaccination is that no pain is associated with it. People would not have to worry about having a sore arm for 24 hours and can continue with their daily lives. My only concern is what possible side effects could occur from this type of vaccine administration?
Immunization has helped contain a lot of major epidemics that have killed so many in the past such as in the case of measles. But because of the fear of both the needles and the trauma it causes in patients, a lot of the parents are not vaccinating to spare themselves of those “unbearable” side effects. Even in today’s age, the breakout of diseases such as polio or even measles which have been dealt with in the past is once again emerging because of lack of vaccination. The idea to remove the use of needles will increase the number of vaccinated individuals in a population, reduce epidemics, and hopefully eradicate diseases. The direct presentation of the antigen through vaccination in the oral mucosal membrane activates memory cells in the immune system to produce antibodies against the given disease. The one question I have is will this method still need booster doses? What are the other benefits besides the “unbearable” needle fear?
I personally agree with needle free vaccines, because of the number of people who are scared of needles they avoid going to the doctors and getting the vaccines they need. Needles can also cause several diseases and injuries to the population. However, because of the steps needed to administer the MucoJet I do not think I would use this specific form of vaccine, mainly because I’d be uncertain if I administered the vaccine correctly. In the article “Transcutaneous vaccination using a hydrogel patch induces effective immune responses to tetanus and diphtheria toxoid in hairless rat” a study was done to administer Transcutaneous immunization (TCI) using a hydrogel patch to tetanus infected rats. The hydrogel patch allows for the antigenic proteins to penetrate the stratum corneum, inducing a toxoid specific IgG production. The usage of both the TCI and hydrogel patch stimulates IgG1, IgG2a, and IgG2b, which results in a Th2-type immune response to bacterial infections, and the formation of an immune memory. Since the patch is simply placed on the skin and left for a certain amount of time I feel like a transdermal vaccination is a lot more convenient than a buccal vaccination.
Needle free vaccines are a unique alternative to typical needle vaccines. The benefits of needle free vaccines are that there is less of a stigma for pain and less of a visual stimulation. On a comparable note, there are nasally administered vaccines, which are a great alternative for needle vaccines. Mucojet does seem to have the benefit of being marketed to younger children. However, A nasally administered vaccine is also just as effective as Mucojet. Nasally administered vaccines also have the benefit of having easy access to the immune system that can also lead to other mucosal sites being stimulated. (1) A focus should be put in to developing various and broad ranging vaccines nasally instead of using resources in developing a completely new system to administrate vaccines. Another detail that was not discussed was whether or not additional vaccines or boosters will be required in addition to Mucojet. If Mucojet can develop a vaccine that is more cost efficient and has has an effectiveness similar to nasal vaccines, then there will be a need for Mucojet.
The idea of administering needle-free vaccines is highly practical, as the article mentions that needle phobia is a common deterrent to becoming vaccinated. Needles may also cause excessive bleeding upon release in individuals that bleed easily. The MucoJet, however, does raise some problems of its own. Self-administration of a vaccine may not be the safest practice for patients in that immunecompromised individuals may experience adverse effects to the vaccines and not even realize it. I also feel that patients should not keep up with their own vaccine records, as it is easy to forget. Healthcare workers are best suited to keep record of immunizations. Also, this article mentions that vaccine administration was carried out on mice and that the buccal region is not the ideal location for injection. I would be curious to see how well the MucoJet translates into human usage, where the site of delivery would be, and how much of the vaccine can be safely tolerated in the human body.
Working in the pharmacy, knowledge of needle free vaccines has been around since the early 2000’s. The vaccine that is needle free is called Flumist and up to this past year it has been used as an alternative to the flu shot for mostly young children but can be used in people up to 49 years old (2). Flumist is a live attenuated strain of the flu virus that is sprayed as an aerosol into each nostril, like a saline nose spray. Up until this last year it was an equal alternative, but according to the CDC the Flumist means of vaccination are not sufficient and were pulled from pharmacy shelves for the 2016-2017 flu season (3). An article published in 2015 tested the new vaccine efficacy and saw a very wide range of seroconversion to protect the children from the strains in the vaccine but found it was overall an effective vaccine for school aged children (1). This article was published back in 2015, and for this reason, I am skeptical of this new needle free vaccine that is presented in this blog post. Especially because it could be given at home instead of at the doctor’s office or at the pharmacy. It might raise compliance initially but with any medication, it could be used improperly and the child might not take the full dose or the parent might forget to give their child the lollypop and this end with the child not getting the correct dosage or not being protected at all. I think the idea is great but the compliance and protection of the children still need to go under extensive research to assure that they are up to the same seroconversion levels of that of a child vaccinated with the needle vaccine.
Compared to conventional vaccine delivery method, oral vaccine delivery system is more effective and easier to perform. The oral vaccine can not only induce systemic antibodies and cell-mediated immunity but also induce the mucosal immune response, such as the induction of secretory IgA (sIgA) antibodies. SIgA is the major antibodies produced in the MALT in human and can block bacteria and viruses attachment and inactive viruses in the epithelial cells (1&2). This article mentions that MucoJet can penetrate the mucosal layer and establish immunity. It seems that a physical method, air pressure, is applied in the MucoJet delivery system. For future development, MucoJet can utilize chemical methods to improve the delivery efficiency. For example, Bilosomes, a ‘niosome-like’ colloidal carrier, can be used to deliver the vaccine (3). Bilosomes do not require special storage condition and are chemically stable. Bilosomes vaccines have developed against different pathogens, including hepatitis B, influenza, and tetanus. With further improvements, oral vaccines can become the game-changer and be widely applied.
I think needle-free vaccines is rather brilliant. By removing the need for needles, you decrease the anxiety that comes with immunizations, and it reduces the risk that a healthcare worker might stick themselves with an infected needling while treating the patient. I do not know if Mucojet is the right route to take; however, doing intradermal injections does not seem like the most efficient way either. In “Toll-Like Receptor 9 Activation Rescues Impaired Antibody Responses in Needle-free Intradermal DNA Vaccination,” it was noted that there was a need for booster injections because while the cell-mediated immune response was substantially elevated, there was a small humoral response towards the vaccine. By having a depressed humoral response, there is no file being kept on the different antigens we are being exposed to. We need our B cells to be activated that way they can create plasma cells. These cells are responsible for our long-term immunity. Even though our skin is “immune-rich,” traditional intramuscular immunizations are still the most effective; however, they still require a high DNA dosage to create an immune response, unlike the intradermal injection(1). There is still a lot of research to be done in the field of needle-free vaccines, but I think this could truly be revolutionary in the field of vaccines. But what about using this method for not just vaccines but for antibiotic shots and steroid shots? Is there a way to administer antibiotics and steroids without the utilization of a needle?
(1) Toll-Like Receptor 9 Activation Rescues Impaired Antibiody responses in Needle-free intradermal DNA Vaccination. https://www.ncbi.nlm.nih.gov/pubmed/27658623
Vaccines have become an essential part of increasing the livelihood of humans since their discovery in 1796. Vaccinations stimulate the production of antibodies in the body in order to provide stronger immunity against a disease. The ability to strengthen an immune response is especially important in countries where diseases like dengue virus are prevalent. Unfortunately, countries highly afflicted by various infectious diseases are underdeveloped and poverty among the people prevents easy access to vaccinations. Mucosal vaccines, like the one presented in this blog, prove to be the perfect solution to inaccessibility to vaccinations. In a study conducted in 2016, intranasal immunizations were proven to facilitate mass vaccinations among undeveloped populations much better than syringe vaccines (1). In addition, the nasal vaccination enhanced the systematic antibody response towards dengue virus much more efficiently than syringe vaccinations (1). Could nasal vaccinations work more efficiently and painless than syringe vaccinations? Or is this the case with only certain types of infectious diseases? How accessible and easy to use are these nasal vaccinations? These are questions that can induce further research on the comparison between the two kinds of vaccination methods. Personally, I prefer the syringe method because, although it is a moment of panic and pain, this method has been full proof for hundreds of years and has only become more effective as medicine develops.
1. “Biomineralized vaccine nanohybrid for needle-free intranasal immunization”- https://www.ncbi.nlm.nih.gov/pubmed/27575530
Vaccines are inevitable for a human’s health, however the process of witnessing a needle being inserted into your skin is somewhat frightening especially when it comes to children. In the case of a TB vaccine for example, it is a scar that will remain with you for the rest of your life which in most cases the administration of that vaccine was painful. With the MucoJet free-needle, patients have the benefit of receiving vaccines without going through the pain of needle. I think this novel technology is good because it saves time by not going to the hospital or witnessing your children being in pain, and can be done at your own convenience. In countries with limited resources where infectious disease are in a vast increasing rate, the demand for vaccines is also increasing thus intranasal vaccination for example facilitates the mass vaccination via needle-free delivery of vaccine through nasal mucosal surfaces. In a study done, the vaccine nanohybrid was obtained by covering the viral surface with calcium phosphate ( CaP) nanoshell, which changed the physiochemical properties of original vaccine, resulting in the increase of mucosal adhesion to the nasal tissues. The vaccine complex enhanced a systemic antibody response that neutralized wild type of dengue virus and promoted the systemic cellular immune responses, presenting the potential of CaP based vaccine biomineralization for the fabrication of needle-free vaccine formulation which is a benefit for countries with little to no resources.
Needle free vaccination is a beneficial way to avoid pain and phobia for patients. These are some factors that cause people to avoid doctors and not be vaccinated. Needles could also cause damage to the skin and, if not sterilized correctly, could cause diseases or infections. I would personally prefer using needleless vaccination because of the painful bruises that I usually have after a needle. In addition to the Mucojet, another article also focuses on noninvasive vaccination through the skin using other methods. The article “Noninvasive Transdermal Vaccination Using Hyaluronan Nanocarriers and Laser Adjuvant” discusses the study done on mice using a type of vaccine carrier called hyaluronan (HA) and laser adjuvant to enhance the immune response to administer the vaccine through the layers of skin (1). Researchers found that this method was successful. I believe that if these studies continue, vaccines and other medication will no longer need a needle to be administered.
Noninvasive Transdermal Vaccination Using Hyaluronan Nanocarriers and Laser Adjuvant.
New and efficient vaccine delivery can positively alter the vaccination experience in young children fearful of sharp needles. Search for new ways to vaccinate has produced many promising alternatives to traditional methods. Needle-free vaccines are not only important because they offer painless medicine delivery, but a needle in a syringe can also be the source of disease transmission. In many hospitals around the world, Needles are re-used after boiling them in a pressure cooker for long hours, which may not destroy all pathogens and transmit them to another person, creating a public health hazard.
In similar attempt to find a painless method of vaccination, South Korean researchers used the laser called Er: YAG to painlessly enter medicine into the skin. The laser, slightly larger than human hair have speed of 30m/second. Due to its high pressure, the laser could easily penetrate targeted depth in the skin and deliver the medicine without spills. Due to its high accuracy, it is believed to have a significant role in vaccine delivery in the future.
After reading the blog post, the concept of oral vaccines intrigued me, so I wanted to learn about them more. The article “Delivery of immunogens to mucosal immune system using an oral inactivated cholera vaccine: a new approach for development of oral vaccines” discussed how an inactivated Vibrio cholera was able to produce a strong response from the host immune system. But this article also talked about the pros and cons of oral vaccines which were particularly instructive for me. The ones that stuck out to me were how oral vaccines were are more cost effective but also the challenges enduring the gastrointestinal tract environment. This latter point is evident now, but I never thought about as a potential issue. And regarding cost (which also mentioned in the abstract of the article discussed in the blog post), I hope that oral vaccines can become more widely used in developing countries to help them fight diseases more effectively. 
The Mucojet is proving to become a formidable alternative to needles due to its convenient way of taking away people’s fear of invasive needles. In comparison to needles, the non-invasive Mucojet delivers the drug faster and generates mucosal immunity. (1) This helps with detecting pathogens on time and eliminating them efficiently before they continue to spread. It also has a dual purpose of increasing antibody production that is locally in the buccal tissue and systemically via the circulation. (1) While it may not be as prevalent as invasive needles, advances in medical technology can help better facilitate safer methods of administering drugs without having to spill any blood.
If anything, I am beyond intrigued of the level of technology invested in vaccine administration. The mechanism of Mucojet is innovative but can be skeptic in a sense of relying on pressure release to penetrate the skin and accessing our antigen presenting cells. Indeed, I would recommend Mucojet if it is effective on humans and cause little, to no side effects. However, the real problem of avoiding immunization is not vaccine administration. Studies show that the most frequently noted reasons for vaccine hesitancy were distrust in vaccination, fear of side effects and lack of awareness on immunization.