Antibodies against a multiple-peptide conjugate comprising chemically modified human immunodeficiency virus type-1 functional Tat peptides inhibit infection.
We demonstrated recently that selective side-chain modification of functional cysteine-rich (Tat(21-40)) and arginine-rich (Tat(53-68)) domains of the HIV-1 Tat protein blocks pathogenic activities of these peptides while retaining their immunological characteristics. In the present study, we have synthesized a multiple-peptide conjugate system comprising modified Tat(21-40) and Tat(53-68) peptides (HIV-1-Tat-MPC). Immunization of mice with this highly homogeneous 10.7 kDa HIV-1-Tat-MPC synthetic construct induced an effective immune response in mice. The antibodies generated against HIV-1-Tat-MPC efficiently suppressed Tat-induced viral replication and significantly reduced HIV-associated cytopathic effects in human monocytes. These results indicate that epitope-specific antibodies directed against functional sites of Tat protein using non-pathogenic peptides inhibit HIV pathogenesis. The HIV-1-Tat-MPC, therefore, has potential for the development of a safe, effective, and economical therapeutic vaccine to reduce the progression of HIV infection.
Devadas
Krishnakumar
K
Immunopathogenesis Section, Laboratory of Molecular Virology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, United States.
Boykins
Robert A
RA
Hewlett
Indira K
IK
Wood
Owen L
OL
Clouse
Kathleen A
KA
Yamada
Kenneth M
KM
Dhawan
Subhash
S
D016915:AIDS Vaccines / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D000939:Epitopes / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D005260:Female; D015696:Gene Products, tat / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015483:HIV Antibodies / Q000096:biosynthesis*; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D018074:Vaccines, Conjugate / Q000276:immunology; D014779:Virus Replication; D054322:tat Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D000939:Epitopes; D015696:Gene Products, tat; D015483:HIV Antibodies; D010446:Peptide Fragments; D018074:Vaccines, Conjugate; D054322:tat Gene Products, Human Immunodeficiency Virus