Immunogenicity of recombinant influenza virus haemagglutinin carrying peptides from the envelope protein of human immunodeficiency virus type 1.
Haemagglutinin (HA), the major surface glycoprotein of influenza virus, is a potent immunogen against which viral neutralizing antibodies are directed. Studies of the three-dimensional structure of HA have identified major antigenic sites on the molecule. We have exploited HA as a carrier for small antigenic regions (epitopes) of the HIV-1 envelope (env) glycoprotein. Using recombinant DNA techniques, the epitopes were inserted in-frame into a known antigenic site of HA to produce HA-epitope chimeras. Guinea-pigs and mice immunized with these chimeras in combination with adjuvant generated significant immune responses against the carrier HA and also produced epitope-specific antibodies that recognized the native whole HIV-1 env. One of the chimeras which contained a V3-loop sequence of HIV-1 env elicited neutralizing antibodies against the homologous strain of HIV-1. The antibodies against HA and the inserted epitopes remained at high levels for up to 72 weeks. Remarkably, these responses were generated with low doses of immunogens containing only nanogram quantities of the inserted epitopes. These results suggest the utility of HA as a carrier to allow selective antibody induction against foreign epitopes, and offer a new approach for vaccine development as well as for the production of monospecific antibodies useful in diagnostics and research.
Kalyan
N K
NK
Division of Biotechnology and Microbiology, Wyeth-Ayerst Research, Philadelphia, PA 19101.
Lee
S G
SG
Wilhelm
J
J
Pisano
M R
MR
Hum
W T
WT
Hsiao
C L
CL
Davis
A R
AR
Eichberg
J W
JW
Robert-Guroff
M
M
Hung
P P
PP
D016915:AIDS Vaccines / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D000939:Epitopes / Q000276:immunology*; D005455:Fluorescent Antibody Technique; D006168:Guinea Pigs; D015497:HIV-1 / Q000276:immunology*; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000276:immunology*; D006801:Humans; D015151:Immunoblotting; D009980:Influenza A virus / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000276:immunology; D014162:Transfection; D014614:Vaccines, Synthetic / Q000276:immunology*
D016915:AIDS Vaccines; D000939:Epitopes; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic