Human immunodeficiency virus-1 principal neutralizing domain peptide-toxin A conjugate vaccine.
To enhance the potential efficacy of peptide-based vaccines for human immunodeficiency virus-1 (HIV-1), a principal neutralizing domain (PND) peptide (KRIHIGPGRAFYT) (HIV-1MN) was covalently coupled to Pseudomonas aeruginosa toxin A (TA). Immunization of guinea-pigs with this conjugate vaccine, in the absence of an adjuvant, engendered a high-affinity antibody response to the homologous HIV-1MN PND peptide and to analogous peptides from variant strains of HIV-1. A substantial proportion of such antibodies was directed to the conserved GPGRAF motif. Anti-PND peptide antibodies were capable of neutralizing the homologous strain, HIV-1MN, in addition to two heterologous (RF, IIIB) variants, as determined either by inhibition of syncytia formation or by suppression of p24 antigen production in cultured cells. Therefore, the method of conjugation used preserved critical neutralizing epitopes expressed by the PND peptide. Monovalent or polyvalent PND-TA conjugates, which meet all safety criteria for human use, are a promising approach towards the development of an acquired immunodeficiency syndrome (AIDS) vaccine.
Cryz
S J
SJ
Swiss Serum and Vaccine Institute, Berne.
Goldstein
H
H
Pettoello-Mantovani
M
M
Kim
A
A
Fürer
E
E
Que
J U
JU
Hasler
T
T
Rubinstein
A
A
D036002:ADP Ribose Transferases; D016915:AIDS Vaccines / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D001427:Bacterial Toxins / Q000276:immunology*; D005098:Exotoxins / Q000276:immunology*; D006168:Guinea Pigs; D015497:HIV-1 / Q000276:immunology*; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010455:Peptides / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000276:immunology; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D016915:AIDS Vaccines; D001427:Bacterial Toxins; D005098:Exotoxins; D010455:Peptides; D018074:Vaccines, Conjugate; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A