[MHT] When it comes to vaccines, everyone now wants to get in on the action. That’s according to Paul Bogorad, a senior manager at pharmaceutical and biotechnology consultancy Putnam Associates in Burlington. Bogorad and other analysts say that the frenzy over H1N1 has heightened the public’s awareness of the difficulty of making vaccines and has intensified companies’ hunger to do it better.

But it wasn’t always so. In the 1970s and ’80s, companies raced to get out of the vaccine business because of the high manufacturing costs, the high chance of failure, and the threat of lawsuits if patients suffered adverse side effects. But then the federal government passed the Childhood Vaccine Injury Act in 1986, which created a pool of money for patients who experienced adverse effects and shielded companies from lawsuits. Advances in technology have driven manufacturing costs down. “And companies have seen that if a vaccine is on a government program, one doesn’t have to spend money to promote it,” Bogorad said.

The market is dominated by a handful of global players, including U.K.-based GlaxoSmithKline, France’s Sanofi Pasteur, Wyeth, which has now merged with New York-based Pfizer Inc., Switzerland’s Novartis AG and Merck and Co. Inc. of New Jersey. This makes it difficult for smaller players to break in.

But this cadre of vaccine giants relies on an ecosystem of smaller companies to fill its pipeline with preventive therapies. And that pipeline could grow now that the Bill and Melinda Gates Foundation has pledged $10 billion to fund vaccine research.

Bogorad said New England provides a ripe landscape for mergers and acquisitions. Case in point is Acambis. The Cambridge company, which has potential vaccines targeting herpes, influenza, dengue fever and West Nile virus, was bought last year by Sanofi Pasteur for $548 million.

One local vaccine company that has been growing independently is Xcellerex Inc. The Marlborough company was founded in 2004, has 120 employees and is cash-flow positive. Xcellerex provides outsourced manufacturing services and equipment, using a disposable system that eliminates the need for steam sterilization of bioreactors used to make vaccines and other biologics. CEO Joe Zakrzewski said the method cuts down on the chances for contamination of vaccines or other products.

Zakrzewski claims that the process can speed up getting a product to market and that clinical trials using the technology can cost one fourth that of clinical trials using traditional biologics manufacturing methods. Xcellerex’s clients include Cambridge-based Acceleron Pharma Inc., whose lead product is a biotherapeutic designed to increase red blood cell and bone formation and is in Phase 2 clinical trials.

Xcellerex also develops its own therapeutics and has launched a Phase 1 clinical trial for a potential vaccine targeting yellow fever. Bogorad and other analysts say that the travel vaccine market is a small segment of the market, but Zakzrewski said there is still money to be made. “Right now, it’s a $100 million market. But 90 percent of the people who need the yellow-fever vaccine don’t get it, because the risks of the current vaccine are too high. So we love it when people say the market is small. We think it could be $1 billion.”

Xcellerex officials say that their vaccine candidate is fundamentally different from current vaccines because it uses a dead virus rather than a live one. Xcellerex has partnered with other companies on manufacturing four or five vaccines in the past. In October, the company announced it would partner with Rockville, Md.-based Novavax to ramp up large-scale manufacturing for its H1N1 vaccine.

The perils of this high-stakes business can be seen across New England. Protein Sciences Corp., in Meridien, Conn., received a blow when the U.S. Food and Drug Administration rejected its potential flu vaccine this fall, because the agency wanted more safety data. Analysts and public health officials had been watching the progress of the potential vaccine because it would represent a novel breakthrough. While current vaccines for influenza are made from fertilized chicken eggs, which is slow and expensive, the Protein Sciences target aims to produce flu cells in caterpillars.

Antigenics Inc., in Lexington, also faced a regulatory setback this fall when European authorities rejected its potential cancer vaccine, called Oncophage. Cancer vaccines have been an elusive target so far, but officials in area companies say that is going to change.

“We (in the industry) are starting to learn from our mistakes. It’s not a matter of if, but when,” said Eric Von Hofe, CEO of Antigen Express Inc. The Worcester-based vaccine developer is working on targets using synthetic peptides, which are protein fragments, that Von Hofe says can be manufactured more quickly than the traditional chicken-egg method. Von Hofe is reporting positive interim results for a Phase 2 vaccine study targeting breast cancer. But so far, no synthetic vaccines have been approved by the FDA.