The current commercial system for influenza vaccine production depends on the culture of virus in embryonated eggs—a strategy that is both costly and poorly scalable. Consequently, a sudden pandemic event with a demand for millions of vaccine doses in a short time could readily overwhelm the available world production capacity. In this communication, we present a process that uses Escherichia coli for scalable production of recombinant vaccine candidates against influenza. A monomeric and a dimeric fragment of hemagglutinin of the Influenza A H1N1/2009 virus were successfully expressed in a BL21 (DE3) pLysS variety of C41 E. coli. We present results from batch processes where induction is made with IPTG and from fed-batch experiments where expression is induced using lactose/glucose pulses. Concentrations in the range of 1.188 to 0.605 g/L of recombinant protein were observed in 2 L stirred tank bioreactors. The genetic construct included an N-terminal histidine tag sequence that facilitated recovery, purification, and proper refolding of the vaccine candidate by affinity chromatography in columns loaded with Ni+2. The proteins produced by this strategy selectively and specifically recognizes antibodies from patients diagnosed as positive to Influenza A H1N1/2009. Overall protein recovery yields between 30.0-34.7% were typically observed. Based on these yields, a production of 4.6X103 doses L-3 day-1 is feasible. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 2013