The Concentration of Carbon Source in the Medium Affects the Quality of Virus-Like Particles of Human Papillomavirus Type 16 Produced in Saccharomyces cerevisiae

There is accumulating evidence that virus-like particles (VLPs) recombinantly produced in Saccharomyces cerevisiae (S. cerevisiae) are characterized by low structural stability, and that this is associated with reduced antigenicity and immunogenicity. However, little attention has been devoted to methods of improving the quality of the VLPs. Here, we investigated the effect of carbon source concentration in the medium on the antigenicity and immunogenicity of human papillomavirus (HPV) type 16 L1 VLPs expressed in S. cerevisiae from the galactose promoter. Media containing 2, 4, 6, and 8% carbon source, composed of both glucose and galactose in equal proportion, were used. VLP antigenicity was enhanced in cultures grown on media with 6 or 8% carbon source, compared to those from cultures with less than 6% carbon source. Moreover, the VLPs obtained from these cultures induced higher anti-HPV16 L1 IgG titers and neutralizing antibody titers in immunized mice than those purified from cultures with less than 6% carbon source. Our results indicate that the concentration of the carbon source in the medium plays a crucial role in determining the antigenicity and immunogenicity of HPV type16 L1 VLPs.