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toc WHO defined vaccine as any preparation intended to produce immunity to a disease by stimulating the production of antibodies (1) **. ** In the developing world a child is 10 times more likely to die of a vaccine preventable disease than a child in the Western World. To protect people against vaccine preventable diseases, the Initiative for Vaccine Research was established (1).

Types of Vaccine
An ideal vaccine must be easy to deliver, maintain lifelong immunity, demonstrate 100% efficacy of a single dose and cost very little but also increase the safety and increase compliance and uptake.

First generation vaccines consist of live attenuated or inactivated/weakened forms of the pathogen (2). Second generation vaccines consist of protein antigens or recombinant proteins (2). DNA vaccines are third generation vaccines that incorporate genetically engineered DNA encoding the antigen for the pathogen (3). DNA vaccines have proven to be one of the most promising applications in gene therapy as they provide both humoral and cell mediated immunity (3).

Every 10 minutes someone in the US is infected with HIV. Therefore, an effacious vaccine is urgently needed as part of a HIV control measure. A major RV 144 HIV vaccine trial in Thailand showed for the first time that a HIV vaccine; a DNA based vaccine could generate modest protection against HIV infection using a two vaccine combination regime – ALVAC and AIDSVAX. Currently, another trial -HVTN 505- is done to observe viral load decline(15). (16)

The public demand for safe and effective vaccines continues to be strong. The challenges of vaccine development go beyond the identification of antigens, adjuvants and suitable delivery methods. Regulatory, technical and manufacturing hurdles must be overcome when transforming a candidate vaccine to the clinic.

Adjuvants are substances that are added to the vaccine antigens to enhance and target the immune response to these antigens such as ISCOMS (immune stimulating complex matrix), and microbial derivatives(4). A number are currently in use in vaccines (oil emulsions and virosomes) and many are still being developed. Improved adjuvants have the capability of lowering the amount of antigen needed and provide a needle-free delivery.

New Vaccines
The HPV vaccine is the world’s first ever cancer vaccine. Cervarix by GlaxoSmithKline covers HPV types 16, 18 and Gardasil by Merck covers HPV types 6, 11, 16, 18. The vaccine consists of virus like particles (VLPs) made from recombinant HPV proteins.(19) The VLPs share the same outer protein coat (LI) as HPV and allows the VLPs to produce an immune response without subjecting the patient to the virus in any way. Global vaccination has the potential to reduce cervical cancer deaths around the world by as much as two-thirds. In addition, the vaccines can reduce health care costs and anxieties related to abnormal Pap tests and follow-up procedures (5).

Malaria and HIV are potentially preventable by vaccines. The main obstacle to the development of a HIV 1 vaccine is the failure to identify viral antigens which broadly stimulate cross-reactive protective antibodies. In P.falciparum variant specific efficacy is the ultimate end point in the design of clinical trials of vaccines(17).(20) A malaria vaccine is currently in phase III trials and if licensed has the potential to save the lives of thousands. Issues surrounding the public health impact of a malaria vaccine include the duration of protection, how efficacy will vary with intensity of transmission, adequate planning for distribution and implementation and most importantly the cost(6). On average African governments spends $ 0.06 per person on malaria control programmes(7). A vaccine would cost $10 per injection. A financing strategy is needed to sustain a long term programme where the benefits of vaccine are seen to outweigh other interventions – bed nets, anti malaria drugs, insecticides etc. (18)

A huge number of societal and scientific challenges appear when a new vaccine is developed. Recently licensed life-saving vaccines have experienced slow introduction and gradual uptake in the developing world. When balancing health needs and national resources policy makers favour the interventions that will have the greatest public impact. Frameworks have been created to aid policy makers in their investigations surrounding new vaccines, which include: Assessing New Vaccines for National Immunization Programmes (8), Framework for assessing vaccines in the Extended Programme on Immunization (9). These frameworks analyse the burden of disease, the expected impact of a vaccine, implementation, financing and supply and distribution issues.

Routes of Administration
Each vaccine that is developed will have a different route of administration that depends on the clinical trials, pharmacological properties (2), and efficacy and safety profile. The route that gives the maximum level of immunity with the least amount of adverse effects and exposure of danger to the patient will be the decided delivery system. At present there are five systems delivery.

__ Oral administration __
The vaccines given orally in the U.S. are rotavirus vaccines (Rotarex and Rotateq) and oral typhoid vaccines (Vivotif)(2). The oral polio vaccine was discontinued in Ireland due to safety issues(10). Advantages of this method include the absence of needles, solving the problem of safe disposal and leading to fewer needle-stick injuries and transmission of blood-borne diseases. They can also be given by a healthcare worker untrained with needles, increasing the availability and access to the vaccine and also its uptake (especially in needle-phobic individuals). Drawbacks include poor absorption levels and degradation in the GIT(11). However strategies of enclosing antigens in liposomes or expressing them in bacterial or viral vectors are currently being examined to prevent degradation.(12)

__ Subcutaneous administration __
This route consists of injecting the contents of the vaccine into the fatty tissue found between the dermis and the muscular layer. Usually on the thigh of a young child and the upper triceps of an adolescent or adult (2). E.g. Varicella and Yellow Fever vaccines.(13)

__ Intramuscular administration __
An Intramuscular vaccine is given directly into the muscle below the dermis and subcutaneous fat layer. Many inactivated vaccines are given in this way, an exception being one type of Meningococcal Polysaccharide vaccine.(2)

__ Intranasal administration __
This method, also known as mucosal delivery is given to the patient via a special sprayer device into the nose. An example is the live attenuated influenza vaccine (LAIV) (2). Mucosal routes also offer both mucosal and humoral immunity, possibly protecting against those diseases contracted through mucosal surfaces. The disadvantages include the live attenuated vaccines reverting to virulence and causing infection in the immune-compromised.(11)

__ Intradermal administration __
This route consists of delivering small quantities of vaccine into the dermis of the skin. The skin is capable of generating both innate and acquired immune responses and this method proves to be and promises to be a very effective method of vaccination in the future.(11) Recent studies suggest that this method is associated with dose reduction of several different vaccines. For example it is known that the immune response following intradermal vaccination of rabies and hepatitis B is equivalent to one tenth of the dosage when given intramuscularly. However this does not apply to the trivalent influenza vaccine.(11) Studies have also shown an increased immune response in patients with chronic medical conditions for hepatitis B, as opposed to intramuscular methods. There are many different techniques and devices used. Examples include the bifurcated needle in smallpox vaccination and the multi-puncture unit used in the BCG.(11)

New Routes of Administration
The development of new or improved routes of administration of vaccines presents many positive opportunities for improvement of the efficacy of our vaccines today and also to minimize all the potential hazards and adverse effects that exist. They must be easily stored and distributed without compromising quality and should reduce the risk of injury and infection to the people that administer them. (11)

The needle-free jet injection is a technique that uses a gas to force a liquid or powder vaccine through the skin, giving it intramuscularly, subcutaneously or intradermally. Studies have shown that this method can produce an immune response equivalent to or better than most other delivery methods. However the WHO discontinued their use when they were believed to be associated with an outbreak of Hepatitis B. Several different jet injectors are now in development phases.(11) A microinjection system is also in development. This system consists of using a tiny hollow micro needle inserted 1.5mm into the skin. Because of its size and gauge, it is painless and barely felt by the patient. A cancer vaccine using this method is currently in its clinical phases of development.(11) Transdermal delivery involving the administering of vaccines topically is also currently being developed. Topical agents and patches are now available that deliver hormones and nicotine but methods of delivering vaccines are still in the early stages of being developed. (11) Transdermal Microneedle arrays are hollow stainless micro needles that have been successful in administering trivalent influenza vaccines. Obstacles faced consist of maintaining dose consistency and investment.(11), (14)

The Future
Vaccination is a very important part of our future. The possibilities and potential in this field are growing by the year and with new advances in medical science and technology the development of new vaccines and delivery systems could eradicate even the commonest of diseases. Ultimately ‘’immunisation saves lives’’ and will save many more in the near future.

__ References __
1. Organisation WH. Vaccines. 2011 Available from: []. 2. Prevention CfDCa. Epidemiology and Prevention of Vaccine-Preventable Diseases 2011. Available from: []. 3. Gregory A Poland cPGmea, Dennis Murray, senior research fellowb, Ruben Bonilla-Guerrero, senior research fellowa. Science, medicine, and the future New vaccine development. BMJ 2002;324:1315. 2002. 4. Dorothea Sesardic RD. European union regulatory developments for new vaccine adjuvants and delivery systems. Elsevier. 2004. 5. ANCI ANCI. Human Papillomavirus (HPV) Vaccines. 2011; Available from: []. 6. Abedon ST. Vaccination. 7. UNICEF. Malaria Facts. 2011; Available from: []. 8. WPRO WPROW. ASSESSING NEW VACCINES FOR NATIONAL IMMUNIZATION PROGRAMMES A framework to assist decision makers. 2000. 9. WHO. Framework for assessing vaccines in the extended programme on immunization. 2011; Available from: []. 10. Immunisation.ie. Childhood Immunisation Vaccine Preventable Diseases: Polio. 2011; Available from: [|www.immunisations.ie/en/childhoodimmunisation/vaccinepreventablediseases/polio/]. 11. Paul Henri Lambert PEL. Intradermal vaccine delivery: Will new delivery systems transform vaccine administration 2008. 12. J Mestecky ZM, S.M. Michalek, C.D. Morrow, R.W. Compans, D.P. Schafer, M.W. Russel. Current options for vaccine delivery systems by mucosal routes. 1997. 13. Immunisation.ie. NIAC Guidelines. 2011; Available from: [|www.immunisations.ie/en/downloads/NIACGuidlines/PDFfile.15476.en.pdf]. 14. __ Sean P Sullivan, 4 __ __Dimitrios G Koutsonanos__,__2__, __4__ __Maria del Pilar Martin__,__2__ __Jeong Woo Lee__,__3__ __Vladimir Zarnitsyn__,__3__ __Seong-O Choi__,__3__ __Niren Murthy__,__1__ __Richard W Compans__,__2__ __Ioanna Skountzou2__ & __Mark R Prausnitz__. ** Dissolving polymer microneedle patches for influenza vaccination ** 2010. 15. http://www.hivresearch.org/research.php?ServiceID=5&SubServiceID=4 16. [] 17. [] POLICY CHALLENGES IN MALARIA VACCINE INTRODUCTION MELINDA MOREE AND SARAH EWART 2004 18. CONQUERING THE INTOLERABLE BURDEN OF MALARIA: WHAT’S NEW, WHAT’S NEEDED: A SUMMARY JOEL G. BREMAN, MARTIN S. ALILIO, AND ANNE MILLS 2004 [] 19. [] 20. []HIV