Even though the National Academy of Science listed it as a top priority in 1999, cytomegalovirus (CMV) vaccine development has languished in a pharmaceutical backwater until recently. It was considered a money pit. "They've spent massive amounts of money already," says Gerd Maul, a virologist at the Wistar Institute in Philadelphia.

But the mood may be shifting because of a completely unrelated virus. "CMV is going to be a target that all these companies are starting to look at, because of the success of HPV," says Vijay Samant, president and CEO of Vical. Samant is referring to Gardasil, the Merck vaccine for human papillomavirus approved this year by the FDA.

A successful CMV vaccine could reach a similar market, but with less controversy. "The real market is females of childbearing age who are CMV-negative," says Samant. Because CMV is not sexually transmitted, giving such a vaccine to all girls at adolescence should not conflict with the religious or moral objections that dogged the HPV vaccine.

Almost all current vaccines are aimed at children, but now vaccinologists are broadening their focus. "A number of people are talking about a sort of adolescent vaccination date or preadolescent vaccination date that would involve papilloma, acellular pertussis, meningococcal vaccine, and conceivably CMV," says Stanley Plotkin, a vaccine development veteran from the Wistar Institute.

The price point is also rising. "The first vaccines, it was expected they would be cheap, a requirement that was never applied to drugs," says Plotkin. Drug prices climbed while vaccine prices remained low, but that's beginning to change.

While Albert Sabin's oral poliovirus vaccine, introduced in the 1960s, sells for $.08 per dose, Maurice Hilleman's recombinant hepatitis B vaccine, introduced in the 1980s, costs $80 for a course of three injections. Samant, who headed Merck's vaccine division before moving to Vical, estimates that the new HPV vaccine will stabilize at about $300-$400 for a course of inoculations.

Those numbers are helping corporate researchers make a better business case. "Vaccines are extremely profitable, because vaccines don't cost much to make, and vaccines also don't have the traditional patent expiration that occurs with pharma. They produce cash flow for a very long period of time," says Samant.

The higher payout is essential for companies in the vaccine business; while production costs of the final product can be low, development costs for modern vaccines are not. For example, Plotkin estimates that the rotavirus vaccine he worked on was in the pipeline for 25 years before its approval in 2006, at a cost of about half a billion dollars.

For a CMV vaccine, a more insidious money problem could arise after it hits the market. The burden of CMV-related birth defects rests mainly on public institutions, while private insurers would bear much of the cost of vaccination. "If you're running an HMO and you don't have anybody in your network who has CMV disease ... you may be reluctant to incur the cost of immunizing everyone," says Jeff Chulay, chief medical officer at AlphaVax in Research Triangle Park, NC.

Government agencies may pressure insurers to go along, though. The 1999 National Academy of Science report estimated that delivering a CMV vaccine to adolescents would cost about $340 million a year in direct expenses and amortized development costs. The payoff, however, would be $1.5 billion in healthcare cost savings, for a net gain of more than $1.1 billion to the national economy. Those figures were based on a pessimistic scenario, in which the vaccine would be only 70% efficacious, and only half the target population would accept it.