Immunization with a novel HIV-1-Tat multiple-peptide conjugate induces effective immune response in mice.
We report here a novel, highly immunogenic synthetic, multiple-peptide conjugate comprising functional domains Tat(21-40) and Tat(53-68) from HIV-1 group M plus Tat(9-20) from HIV-1 group O of the HIV-Tat protein (HIV-1-Tat-MPC). Vaccination of mice with HIV-1-Tat-MPC induced an effective immune response to all three functional domains. The anti-HIV-1-Tat-MPC antibodies efficiently inhibited Tat-induced viral activation in monocytes infected with HIV(Ba-L) as well as with various clinical HIV-1 isolates, and reduced Tat-mediated cytopathicity in infected cells by 60-75%. Our results indicate that anti-HIV-1-Tat-MPC antibodies inhibit viral pathogenesis, possibly by blocking functional determinants of Tat and disrupting autocrine and paracrine actions of secreted Tat protein. This epitope-specific, synthetic Tat construct may, therefore, provide a subunit AIDS vaccine candidate for inducing an effective immunoprophylaxis response to reduce progression of HIV infection.
Boykins
R A
RA
Laboratory of Parasitic Biology and Biochemistry, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
Ardans
J A
JA
Wahl
L M
LM
Lal
R B
RB
Yamada
K M
KM
Dhawan
S
S
D016915:AIDS Vaccines; D000163:Acquired Immunodeficiency Syndrome / Q000517:prevention & control; D000818:Animals; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D015696:Gene Products, tat / Q000378:metabolism*; D015658:HIV Infections / Q000517:prevention & control*; D008264:Macrophages / Q000378:metabolism / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008956:Models, Chemical; D009000:Monocytes / Q000378:metabolism / Q000821:virology; D010455:Peptides / Q000737:chemistry; D017434:Protein Structure, Tertiary; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013154:Spleen / Q000378:metabolism / Q000821:virology; D013997:Time Factors; D054322:tat Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D000939:Epitopes; D015696:Gene Products, tat; D010455:Peptides; D054322:tat Gene Products, Human Immunodeficiency Virus