Peripherally biased distribution of antigen proteins on the recombinant yeast-derived human hepatitis B virus surface antigen vaccine particle: structural characteristics revealed by small-angle neutron scattering using the contrast variation method.
The internal structure of the recombinant yeast-derived human hepatitis B virus surface antigen vaccine particle was investigated by small-angle neutron scattering using the contrast variation method. Data were collected in aqueous buffer solutions containing 0, 40, 60, and 100% D2O in the q range of 0.005 to 0.2 A-1 at 5 degrees C. The radius of gyration at infinite contrast and the maximum dimension of the particle were estimated to be 107 and 290 A, respectively. The contrast matching point of the particle was determined to correspond to about 30% D2O, indicating that a considerable portion of the vaccine particle is made up of lipids and carbohydrates from yeast. The distance distribution function of the particle at 40% D2O, at which the protein components are matched out to show only the distribution of the remaining lipids and carbohydrates, differed markedly from the functions at other D2Os, and showed the nearly symmetrical profile characteristic of a spherical particle with a diameter of 240 A. The Stuhrmann plot and profile of the distance distribution function at 40% D2O showed that (i) the vaccine is a spherical particle with a diameter of 290 A, in which two different regions in terms of scattering density are distributed radially, (ii) the lipids and carbohydrates form a spherical cluster with a diameter of 240 A in the core region of the particle, and (iii) the surface antigen protein is present in the peripheral region. This architecture of the vaccine particle is favorable for the induction of anti-virus antibodies.
Sato
M
M
Institute for Protein Research, Osaka University.
Sato-Miyamoto
Y
Y
Kameyama
K
K
Ishikawa
N
N
Imai
M
M
Ito
Y
Y
Takagi
T
T
D003001:Cloning, Molecular; D016679:Genome, Viral; D006514:Hepatitis B Surface Antigens / Q000737:chemistry*; D017325:Hepatitis B Vaccines / Q000737:chemistry*; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D006801:Humans; D008433:Mathematics; D008961:Models, Structural; D009502:Neutrons; D011487:Protein Conformation; D012441:Saccharomyces cerevisiae; D012542:Scattering, Radiation; D014614:Vaccines, Synthetic / Q000737:chemistry*
D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D014614:Vaccines, Synthetic