General, Infant and Children | November 3, 2015 | Author: The Super Pharmacist
Immunisations are a cruel rite of passage for parents. Parents love their children and want them to be protective against crippling, disabling, and lethal diseases; however, they must subject their infants and children to a gauntlet of injections. Often, this leads to a fear of needles that may last through childhood, adolescence, and into adulthood. This fear leads people to avoid healthcare services and immunisation even as adults. Fortunately, new research is leading to advances in vaccine delivery systems that may allow people to avoid needles when obtaining much-needed immunisations.
Patients often wonder why they cannot simply take a pill for their immunisations. The answer is that the stuff of drugs and the stuff of vaccines are fundamentally different. Most drugs are small molecules that are reasonably resistant to the ravages of the digestive system.
Swallow one little pill and the drug is eventually absorbed by the gastrointestinal tract, is carried through the blood, and reaches the cells of the body. The immune system usually ignores the small molecules as they course through the blood. Vaccines, on the other hand, have a different goal and different structure.
Vaccines are designed to provoke the immune system. They are traditionally made out of peptides, proteins, other large molecules, or even whole cells. The digestive system is very effective at digesting and metabolising these large molecules. As a result, swallowing a traditional vaccine in pill form would be a waste—the digestive system would destroy the vaccine before the immune system could detect it and react to it.
Therefore, the main goal of vaccine delivery systems is to protect the vaccine from being metabolised destroyed by the body so that it can reach the bloodstream to provoke an immune response.
Ideally, vaccines could be given orally. In order to do that, however, the vaccine would have to be protected from high acidity in the stomach and a barrage of enzymes produced by the body (mainly in the pancreas) that aim to break apart (metabolise) peptide/proteins.
There are several ways to protect the vaccine on its way from the mouth to the bloodstream:
There are other ways to get large molecules into the body besides an injection through the skin or by swallowing a pill. A vaccine can be introduced to the immune system by simply crossing special areas of the body called mucosa. Mucosa allows substances to pass across it into the bloodstream much more readily than the skin does.
Several places in the body contain mucosa, but researchers are focusing on three in particular, namely the nasal, oral, and pulmonary mucosa. In fact, there are several commercially available vaccines that are administered nasally (e.g. nasal influenza vaccine).
Nasally administered vaccines do not face digestive acid and enzymes in the mouth, stomach, or intestines. Moreover, the mucosa is richly supplied with immune system cells that will (ideally) recognise the vaccine, initiating the desired immune response.
Unfortunately, the mucosa works to “tolerate” rather than “recognise” antigens, including vaccines. Therefore, researchers must develop ways to defeat the body's natural tendency towards tolerance in order to stimulate an immune response. Mucosal vaccines, for example, can be enhanced by combining the vaccine with nanoparticles/nanogels that increase uptake by immune system cells (i.e. lymphoid cells).
As mentioned, oral and nasal mucosae are not the only mucosa in the body. Mucosa can be found in the rectum and vagina as well. Indeed, these locations are currently being targeted for vaccine development against sexually transmitted infectious diseases such as HIV and genital herpes. Another alternate route for vaccine administration is through the eye. Eye drops can be used to deliver vaccine onto the surface of the eye that is taken back into the mucosa near the tear ducts. While eye drop vaccines are only in early development, early results are promising.
One of the more provocative potential methods for vaccine delivery is to infect patients with a virus or bacterium that does not cause human disease, but that has been genetically modified to produce antigens (i.e. the molecules that induce an immune response during an immunisation). One newer example is to use an attenuated (alive, but harmless) salmonella bacterium that has been designed to produce one or more antigens of interest. The salmonella vaccine can be taken orally and make it into the bloodstream, much the same way that harmful salmonella can cause salmonella poisoning. At least six clinical trials using attenuated Salmonella vaccines have yielded positive results.
For those who fear needles would simply rather avoid them, alternative vaccine delivery routes offer hope. Intranasal flu virus vaccines are already available, as are oral polio vaccines. Researchers are developing novel delivery mechanisms for vaccines against a variety of infectious diseases including:
It is too early to tell whether these vaccines will successfully proceed through development and become available to the public. That said, the arrow of progress seems to point toward a day in which most common immunisations will be delivered without a needle.
1. Wright S, Yelland M, Heathcote K, Ng SK, Wright G. Fear of needles--nature and prevalence in general practice. Aust Fam Physician. Mar 2009;38(3):172-176.
2. Saroja CH, Lakshmi PK, Bhaskaran S. Recent trends in vaccine delivery systems: A review. International Journal of Pharmaceutical Investigation. Apr-Jun 2011;1(2):64-74. doi:10.4103/2230-973x.82384
3. Kraan H, Vrieling H, Czerkinsky C, Jiskoot W, Kersten G, Amorij JP. Buccal and sublingual vaccine delivery. J Control Release. Sep 28 2014;190:580-592. doi:10.1016/j.jconrel.2014.05.060
4. Carter NJ, Curran MP. Live attenuated influenza vaccine (FluMist(R); Fluenz): a review of its use in the prevention of seasonal influenza in children and adults. Drugs. Aug 20 2011;71(12):1591-1622. doi:10.2165/11206860-000000000-00000
5. Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature. Mar 19 1998;392(6673):245-252. doi:10.1038/32588
6. Fujkuyama Y, Tokuhara D, Kataoka K, et al. Novel vaccine development strategies for inducing mucosal immunity. Expert Review of Vaccines. 2012;11(3):367-379. doi:10.1586/erv.11.196
7. Tengvall S, O'Hagan D, Harandi AM. Rectal immunization generates protective immunity in the female genital tract against herpes simplex virus type 2 infection: relative importance of myeloid differentiation factor 88. Antiviral Res. Jun 2008;78(3):202-214. doi:10.1016/j.antiviral.2007.12.014
8. Tengvall S, Lundqvist A, Eisenberg RJ, Cohen GH, Harandi AM. Mucosal administration of CpG oligodeoxynucleotide elicits strong CC and CXC chemokine responses in the vagina and serves as a potent Th1-tilting adjuvant for recombinant gD2 protein vaccination against genital herpes. J Virol. Jun 2006;80(11):5283-5291. doi:10.1128/jvi.02013-05
9.Knop E, Knop N. Lacrimal drainage-associated lymphoid tissue (LDALT): a part of the human mucosal immune system. Invest Ophthalmol Vis Sci. Mar 2001;42(3):566-574.
10. Roland KL, Brenneman KE. Salmonella as a vaccine delivery vehicle. Expert Rev Vaccines. Sep 2013;12(9):1033-1045. doi:10.1586/14760584.2013.825454