Assembly, structure, and antigenic properties of virus-like particles rich in HIV-1 envelope gp120.
In order to improve the immunogenicity of HIV-1 envelope glycoproteins, we have fused gp120 to a carrier protein, hepatitis B surface antigen (HBsAg), which is capable of spontaneous assembly into virus-like particles. The HBsAg-gp120 hybrid proteins assembled efficiently into 20-30 nm particles. The particles resemble native HBsAg particles in size and density, consistent with a lipid composition of about 25% and a gp120 content of about 100 per particle. Particulate gp120 folds in its native conformation and is biologically active, as shown by high affinity binding of CD4. The particles express conformational determinants targeted by a panel of broadly cross-reactive neutralizing antibodies, and they show tight packing of gp120. Because the particles are lipoprotein micelles, an array of gp120 on their surface closely mimics gp120 on the surface of HIV-1 virions. These gp120-rich particles can enhance the quality, as well as quantity, of antibodies elicited by a gp120 vaccine.
Berkower
Ira
I
Laboratory of Immunoregulation, Division of Viral Products, Office of Vaccine Research and Review, Center for Biologics, Bethesda, MD 20892, USA. Berkower@cber.fda.gov
Raymond
Megan
M
Muller
Jacqueline
J
Spadaccini
Angelo
A
Aberdeen
Anne
A
D016915:AIDS Vaccines / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis / Q000276:immunology*; D016367:Baculoviridae / Q000378:metabolism; D001483:Base Sequence; D018604:Epitope Mapping; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000648:ultrastructure; D007114:Immunization; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000276:immunology* / Q000648:ultrastructure; D014614:Vaccines, Synthetic / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics / Q000378:metabolism
D016915:AIDS Vaccines; D000914:Antibodies, Viral; D015699:HIV Envelope Protein gp120; D006514:Hepatitis B Surface Antigens; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic