It was Edward Jenner, a British country doctor, who made medical history in the 18th century after observing that milkmaids who developed blisters from cowpox were immune to its deadly human counterpart smallpox.

Another key player in the discovery, James Phipps, didn't get a lot of credit for his role in Jenner's development of a small pox vaccine. Phipps was the eight-year-old boy who provided "proof of concept" in 1796 after Jenner took pus from the blisters of a milkmaid and broke Phipps' skin to infect him with cowpox. That was centuries before those pesky institutional review boards began sticking their noses in everyone's business. Phipps was then repeatedly exposed to smallpox to demonstrate his immunity during the following 20 years.

I thought of Phipps the other day while speaking with Vijay Samant, president and CEO of the San Diego-based Vical. During our conversation, Samant asked me several times whether I would like him to inject me with a vaccine that contained live HIV or other deadly pathogens. I politely declined. He was trying to make a point about the benefits of Vical's DNA vaccines, but one he returned to just a little too often in our conversation. I got it the first time, but he wanted to make sure.

San Diego-based Vical has been around since 1987, but it's been transformed since Samant left Merck as the chief operating officer of its vaccine division at the end of 2000 to take the helm of the small biotech. He already knew the company and its technology well through ongoing collaborations between Vical and Merck. Since joining the company, he has shed most of its non-vaccine programs, overhauled senior management and brought in additional vaccine expertise as he doubled the staff to 150 employees.

Unlike conventional approaches to vaccine that inoculate people with dead or weakened viruses, Vical uses plasmids—unique loops of segments of DNA of pathogens—to train the body's immune system to fight possible future infections. These plasmids encode proteins that are associated with specific pathogens. The vaccine teaches the bodies immune system to recognize these proteins and so it can mount an immune response if they every show up with the pathogen to which they belong. When The company said its DNA vaccines can induce potent antibody and T-cell immune responses.

Such an approach has many advantages over conventional vaccine development and manufacturing. Samant said once the company has the genome of a pathogen, it could develop a vaccine in a matter of weeks. Because it is producing plasmids, it can use conventional biotech manufacturing of fermentation to produce the vaccine.

Shorter Manufacturing Time
Conventional vaccine production methods using eggs to grow the vaccine take substantially longer—about seven months compared to about two months—and are not scalable. In the event of a pandemic or bioterrorism attack, capacity could easily be added. In addition, the shorter time to manufacturing could allow better targeting of seasonal flu vaccines because guesses about the likely strains of flu to attack would not need to be made so far in advance of flu season.

"It's like Saks or Nordstrom predicting what the fashion is going to be a year down the road and places orders in China and India and all of the sudden the girls in New York don't want to wear polka dots," said Samant, referring to the current lag times in vaccine manufacturing.

Vical, though, has been working on an alternative approach to producing its DNA vaccines that it says could allow it to produce several million doses in a matter of days. Instead of using a bacterial fermentation process, the company is developing a production process that relies on polymerase chain reaction or PCR, a method for amplifying DNA. The technology has been traditionally used in such applications as diagnostics, research or forensics. Through this process, minute amounts of DNA are replicated so they can be more easily detected and are easier for researchers with which to work.

Government Takes Notice
The U.S. Government has taken an interest in Vical's work. Earlier this month, the National Institute of Allergy and Infections Diseases awarded the company a three-year, $6-million grant for further development of its so-called RapidResponse DNA Vaccine platform. Instead of a plasmid, which includes DNA sequences needed by the bacteria used in the fermentation process, the PCR process produces a small segment of DNA called a linear expression cassette. This includes only those DNA sequences essential for the specific vaccine.

"This would be a huge breakthrough. That's why we got the money," said Samant. "Six million is not peanuts for a small company."

The company continues development of its plasmid DNA vaccine programs because the technology is much closer to reaching the market. Currently, Vical is developing plasmid DNA vaccines against pandemic influenza, CMV, HIV, Ebola, West Nile virus and SARS. But it said its RapidRepsonse system could further cut the cost of production and increase the speed of producing vaccines.

Which brings me back to Jenner and the eight-year-old Phipps, who actually lived until he was 65 and never suffered from smallpox. Having blister pus introduced into your bloodstream may not have been the most inviting approach to vaccination I can imagine. But in a strange way, it does represent a goal of sorts for vaccine makers: It was fast, cheap and most of all, the damn thing worked.