THE FUTURE OF VACCINES AND VACCINATION

October 11, 2008 by craig

It is evident that currently vaccine research is a vigorous and developing topic but a number of goals remain elusive. For example, an ideal vaccine should elicit the required immunological response against specified pathogens, whether it requires a specialized delivery system or adjuvants. This entails comparison of the requirements for an ideal vaccine, with progress to date.

In addition it is becoming clear that vaccines should be heat stable since many are required in tropical countries where the cold supply chain used for many current vaccines is not available. Any newly developed vaccine must be completely safe since it should not cause disease or manifest side effects. This consideration is difficult to achieve in many cases because the side effects may not always be evident at first and may only show up after thousands of patients have been treated, often as an idiosyncratic reaction in just a few individuals. This issue is also experienced when developing small molecule drugs for the market place.

An advantage would be obtained if protection could be achieved using only a single dose that would be effective for the rest of the patients life. In some instances a controlled-release formulation has been tested and pulsatile systems that could mimic the administration of a booster dose may also have the desired effect.

Finally, the vaccine must be inexpensive and this is by no means an easy requirement. To illustrate the point, if a vaccine costs $25 to produce, pack, and deliver to the patient, how can this be acceptable in a country where the amount of money available per patient is only $250 per annum? Of course, money is saved on the subsequent savings in healthcare costs throughout the remainder of the patient’s life. The rest of the debate is limited to a discussion of the value of a life, but in human terms this cannot be measured.

An interesting issue has surfaced at the time of writing (October 2004) when the supply of influenza vaccine in both the United States and United Kingdom became severely limited owing to a failure in good manufacturing practices within one organization. This resulted in the closure of the plant involved but, more to the point, a loss of about 50% of available doses for the winter season. Since there are only two plants worldwide making this vaccine, this has affected affluent members of society who would otherwise not consider themselves affected by the economic constraints that affect developing nations. The media has probably contributed to the hysterical discussion of which members of society should or should not receive the vaccine, also promoted by some politicians as the vaccine that could make the difference between life or death. The more responsible media has suggested that there may be insufficient economic return and too high a commercial risk for many pharmaceutical manufacturers to wish to get involved in vaccine production in general so that failures of this magnitude are almost inevitable. This entire issue will not go away and it is certain the discussion will continue in the foreseeable future.

On the basis of current research it may be possible to speculate about future directions for vaccine development. For example, controlled-release drug systems are well recognized and have appeared in clinical practice. It seems reasonable to ask if the same technology could be applied to vaccines. What would be ideal is a vaccine that only required a single dose which incorporated that booster dose so often necessary for complete effectiveness. If this in turn was combined with heat stability to overcome the problem of maintaining an effective cold chain for distribution in tropical countries we would be well on the way to providing an ideal product.

The probability is that acellular and subcellular vaccines will represent the future because they are generally much safer although, without appropriate adjuvants, they may be less effective. Viral shells, without their DNA should not be able to grow in vivo but should be capable of triggering an immune response in the form of the production of antibodies and memory cells. Isolated bacterial flagellae may also be capable of the same response. Acellular vaccines against Haemophilus influenzae B (Hib) bacterial flagellae have been cultivated and tested. An anthrax vaccine uses the protective antigen of anthrax, and there have been a number of attempts to develop a vaccine against the GP 120 surface protein of the HIV virus.

Recombinant DNA vaccines offer alternatives as subunit vaccines and organisms can be engineered to produce antigens or even epitopes. A hepatitis B vaccine has been engineered using yeast as the host cell. Adverse reactions are rare to subunit vaccines, making them safer for use in immunocompromised patients.

A recent development has been the use of genetically modified plants to produce vaccine components. Examples include common foodstuffs such as tomatoes, bananas, potatoes, and corn. The prospects for oral vaccines in bananas especially would appear to be promising since this is a staple food in many tropical countries. Vaccine epitopes have also been produced in the milk of goats, sheep, and cows although these may be difficult to purify, process, and formulate.

Bacterial toxins such as diphtheria and tetanus can damage host cells but the isolated toxins can also be immunogenic. However, the induced response may not always be very strong and booster shots are required every 10 years. Adjuvants could improve the response and both diphtheria and tetanus toxoids are more effective when combined with pertussis subunit vaccines, the DPT combination at present used clinically.

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