There’s a Shot for That

On May 14, 1796 Edward Jenner injected fluid from the cowpox blisters on the hands of dairymaid Sarah Nelmes, into James Phipps, an 8-year-old boy.  Jenner hoped the fluid from the cowpox lesion would somehow inoculate the boy against the smallpox scourge which at the time was killing over 400,000 Europeans a year. His hunch proved correct.

Today vaccines save 3 million lives per year worldwide. By training the human immune system to recognize and ward off dangerous pathogens, vaccines can protect against disease for decades, or even for a lifetime. Preventive vaccines work by introducing harmless microbial chemical markers, known as antigens, which resemble the markers on living microbes. The antigens train the immune system to recognize and destroy those microbes should they ever appear in the body. By injecting cowpox antigens into Phipps bloodstream, Jenner primed his immune system to attack the similar smallpox virus.

Now, medical scientists are taking Jenner’s ideas in a whole new direction. By exploiting a growing understanding of the immune system they are developing therapeutic vaccines targeting established diseases rather than trying to prevent them.

Last spring, the FDA approved Provenge, a personalized immunotherapy that activates a patient’s own immune cells to target and attack advanced prostate cancer. To make the Provenge prostate cancer vaccine, biochemists at Seattle’s Dendreon Corporation extract a sample of a patient’s own immune cells and bathe them in a chemical soup of prostate cancer antigens that are chemically linked to a cytokine that screams, “Attack this!”.  The activated immune cells are then injected back into the patient’s body to spread the call to arms.

While Provenge was the first of the new generation of therapeutic vaccines, it’s certainly not the last. BCC Research has identified 113 therapeutic vaccines in development, many of which are already in human trials. They even go so far as to estimate that the market for therapeutic vaccines will have an annual growth rate of 115% and reach an estimated $2.9 billion in 2014.

Other cancer vaccines are among the front runners. With a near-endless supply of patients willing to undergo novel treatments, cancer researchers have been among the most aggressive in experimenting with therapeutic vaccination. The Cancer Vaccine Collaborative is working on treatments that target multiple cancer antigens, which should trigger a more aggressive immune response and increase the odds of defeating tumors. All of which is good news for the 1.5 million Americans diagnosed with cancer each year.

While cancers cause a proliferation of diseased cells, some autoimmune diseases, cause the cells of the immune system to turn against healthy tissues. In diabetes, for example, the immune system attacks insulin-making pancreatic beta cells.

In multiple sclerosis, it’s the myelin sheaths that are designed to protect the nerves that come under attack.

Autoimmune vaccines hold the promise of shutting down these attacks. One promising approach boosts T-regulatory cells, a subgroup of the white blood cells. At the University of Calgary’s Diabetes Research Centre in Alberta, immunologist Pere Santamaria has attached a cocktail of antigens from pancreatic beta cells to synthetic iron oxide nanoparticles. This stimulates the development of T-regulatory cells into killer T cells that destroy the immune cells which cause the serial killer like autoimmune attack.

Santamaria’s team recently tested his vaccine in diabetes-prone mice. It restored normal blood sugar and insulin levels in animals that already had diabetes and prevented or slowed its onset in young mice that had not yet developed the disease. The team is now readying the vaccine for human trials and is designing related vaccines to treat other autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease.

If effective, such therapeutic vaccines could help the three million Americans with type 1 diabetes and the 400,000 people diagnosed with multiple sclerosis. Vaccines against dust mites and asthma are also in the works.

Some of the new therapeutic vaccines are actually designed to attack the body, albeit in a selective way. A new experimental heart-disease vaccine takes aim at unwanted biochemicals within the body, specifically low-density lipoprotein (LDL), better known as bad cholesterol. When large quantities of LDL cholesterol circulate through the bloodstream, it can be deposited on artery walls, leading to a buildup of plaque and triggering inflammation. Anti-cholesterol vaccines encourage the immune system to attack LDL and remove plaques. Scientists have also discovered that the vaccine lowers blood pressure and protects against the rupture of aneurysms, at least in mice.

Clinical trials in humans are expected to start later this year and if successful could help to prevent the 800,000+ deaths per year from cardiovascular disease.

Even more people could be helped by an anti-obesity vaccine. Nearly 75 million adults are classified as obese in the United States. Researchers are working on a vaccine that targets ghrelin – a gastrointestinal hormone that appears to stimulate appetite.

Others, are looking at vaccines to prevent addiction to cocaine, methamphetamines, opiates and nicotine.

It is too soon to know how and when these vaccines will come to market or how effective they will be, but it’s clear that therapeutic vaccines are coming and will be used against a host of the most prevailing public health issues of the 21st century.

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