Abstract.— Four different vaccination regimes, including non‐vaccinated controls (C), immersion/oral combination (IO). late immersion (LI), and injection (IJ), were evaluated for antibody production and protection from challenge in channel catfish Ictalurus punctatus that were hatched and raised in recirculating culture systems over a 28‐wk period. For IO, fry were vaccinated by immersion on day 12 post‐hatch and given an oral booster during week 10 post‐hatch. The LI and IJ delivered vaccine was also administered at week 10 post‐hatch. No titers were detected in the IO group prior to the oral booster at week 10. Mean titers rose sharply after the week 10 vaccinations in all treatment groups, maintained a high level for about 8 wk, and slowly declined over the next 4 wk. Injected fish had significantly higher titers during the primary response period than either LI or IO fish. There was no statistical difference in titers between LI and IO fish during the primary response. After an oral booster delivered during week 22, titers in LI and IO fish increased significantly at week 25, while titers in IJ fish declined despite the booster delivery. An immersion booster delivered during week 25 resulted in significant increases in titers in all vaccinated groups. Of multiple challenges, the only one not marred by concurrent columnaris infections revealed a low, but significant level of protection in IJ fish at 12 wk post‐vaccination.