Among high-antibody producers, 53% were abstinent from cocaine more than half the time, compared with 23% of people who made lower levels of antibodies.
No serious side effects were reported. The study was published in the Archives of General Psychiatry.
The antibodies eventually subside over a period of weeks, so booster shots would be required, and more work is needed to improve the response rate, Kosten said.
"This is a first-generation vaccine, and we wanted something simple and safe to show it works," he said.
The National Institute on Drug Abuse will fund a larger study of the cocaine vaccine beginning in January.
People who want to quit smoking already have several behavioral and pharmaceutical treatments to choose from, but there are no medical treatments for cocaine use, methamphetamine or PCP dependence. Methadone is only modestly effective in treating heroin addiction.
However, need and desire may not be enough to move vaccine technology to the market.
"Drug manufacturers shy away from addiction treatments due to liability," Kosten said. "They are afraid that if someone has an overdose later, they would blame it on what the vaccine did to their body. We have people lining up and down the street to take the vaccine. It's almost a no-brainer. The problem is we have to get by this huge legal barrier."
The vaccine approach won't work to treat alcohol addiction because alcohol molecules are simply too small and shapeless to tether to larger proteins, said Baylor's Kinsey.
It's also not likely to work for marijuana because the active chemical -- THC -- is extremely sensitive to light, air, heat and acid, all of which makes it difficult to manipulate in the laboratory, she said.