Antibodies with specificity to native gp120 and neutralization activity against primary human immunodeficiency virus type 1 isolates elicited by immunization with oligomeric gp160.
Current human immunodeficiency virus type 1 (HIV-1) envelope vaccine candidates elicit high antibody binding titers with neutralizing activity against T-cell line-adapted but not primary HIV-1 isolates. Serum antibodies from these human vaccine recipients were also found to be preferentially directed to linear epitopes within gp120 that are poorly exposed on native gp120. Systemic immunization of rabbits with an affinity-purified oligomeric gp160 protein formulated with either Alhydrogel or monophosphoryl lipid A-containing adjuvants resulted in the induction of high-titered serum antibodies that preferentially bound epitopes exposed on native forms of gp120 and gp160, recognized a restricted number of linear epitopes, efficiently bound heterologous strains of monomeric gp120 and cell surface-expressed oligomeric gp120/gp41, and neutralized several strains of T-cell line-adapted HIV-1. Additionally, those immune sera with the highest oligomeric gp160 antibody binding titers had neutralizing activity against some primary HIV-1 isolates, using phytohemagglutinin-stimulated peripheral blood mononuclear cell targets. Induction of an antibody response preferentially reactive with natively folded gp120/gp160 was dependent on the tertiary structure of the HIV-1 envelope immunogen as well as its adjuvant formulation, route of administration, and number of immunizations administered. These studies demonstrate the capacity of a soluble HIV-1 envelope glycoprotein vaccine to elicit an antibody response capable of neutralizing primary HIV-1 isolates.
VanCott
T C
TC
Henry M. Jackson Foundation, Rockville, Maryland 20850, USA. tvancott@hiv.hjf.org
Mascola
J R
JR
Kaminski
R W
RW
Kalyanaraman
V
V
Hallberg
P L
PL
Burnett
P R
PR
Ulrich
J T
JT
Rechtman
D J
DJ
Birx
D L
DL
D000276:Adjuvants, Immunologic; D000818:Animals; D000954:Antigens, Surface / Q000276:immunology; D019281:Dimerization; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D005434:Flow Cytometry; D015483:HIV Antibodies / Q000096:biosynthesis*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D019302:HIV Envelope Protein gp160 / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D009500:Neutralization Tests; D011817:Rabbits; D011994:Recombinant Proteins
D000276:Adjuvants, Immunologic; D000954:Antigens, Surface; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D011994:Recombinant Proteins