SOME FUTURE VACCINE OPPORTUNITIES

October 11, 2008 by craig

There appear to be a myriad of opportunities for vaccines against, for example, cancers, allergies, hepatitis, tuberculosis, and HIV. Vaccines to treat drug addicts, including tobacco products, nicotine, and cocaine are all within the realm of possibility. There is a perceived need to develop effective vaccines against bovine spongiform encephalopathy (BSE) and the human form, new variant Creutzfeldt-Jacob (nvCJ) disease. Organ transplant vaccines would obviously be beneficial and tetanus toxoid has been shown to lower cholesterol in animals. Tumor-specific antigens have also been explored and heat stress proteins have been evaluated as adjuvants in this case.

Attention has recently become focused on epidermal administration of vaccines, either as polymer rods inserted subdermally or by particulate systems fired into the skin using the high pressure jets developed by companies such as PowderJect Pharmaceuticals (Oxford, UK). The epidermis contains immune cells and less vaccine may be required to achieve a response which also reduces costs.

RISK-BENEFIT RATIOS

The increased used of vaccines has drawn attention to ethical issues associated with safety and the risk–benefit ratio in some cases has come under scrutiny. Vaccines are usually given to patients who are otherwise healthy and have a lower tolerance for risk. Adverse reactions are either quite common (>>10%) or very rare (<<0.0001%). The question of justifiable risk in a healthy population then becomes problematic and difficult to identify.

To identify a justified risk in a healthy population requires clinical trials and if the risk is very low inordinate numbers of patients are required to identify issues. These become extremely expensive in practice and this is one reason why vaccines are subject to postlicencing and postmarketing surveillance for safety.

Animal models are rarely valuable in predicting human responses. Animals are required to be immunized twice monthly and monitored for at least 6 months. Some reassurance might be provided if there were no deaths or obvious and unusual effects. However, postmortem examination is required to ensure that no macroscopic or microscopic changes have been produced in any of the internal organs.

Once the animal studies are completed human studies can commence, moving through phase I (up to 50 naive patients to establish a sufficient immune response); phase II (several hundred patients in several locations) to phase III in which expanded studies on as many as thousands of patients. The trials require to be randomized and closely controlled by being blinded to avoid bias in interpretation. The patients all have to provide informed consent and strict adherence to good clinical practices in accordance with ethical principles is required to ensure risk-benefit considerations justify the risks associated with all trials of this type. The safety of the patients is an overall requirement and trials must be supervised by the appropriate independent ethics committee or the local Institutional Review Board.

It should be noted that, despite all these precautions, some individuals have become impatient with the system and have tried to take shortcuts, with inevitable severe repercussions when things go wrong. The system is there to protect the patients and the complexity of these issues certainly accounts for the high cost of commercially
available vaccines (and drugs in general).

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