Highly attenuated HTLV type Ienv poxvirus vaccines induce protection against a cell-associated HTLV type I challenge in rabbits.
The entire envelope protein of the human T cell leukemia/lymphoma virus type I (HTLV-I)1711, obtained from the DNA of a West African healthy HTLV-I-infected patient, was expressed in the highly attenuated poxvirus vaccine vectors ALVAC and NYVAC. These live recombinant vaccine candidates were used to immunize New Zealand White rabbits. Immunization regimens included inoculation of the poxvirus recombinant alone as well as prime/boost protocols using gp63 HTLV-I envelope precursor protein in Alum as the subunit boost. All animals were exposed to an HTLV-I cell-associated challenge (5 x 10(4) cells) from a primary culture of the HTLV-IBOU isolate. The results indicated that two inoculations of the ALVAC-based HTLV-Ienv vaccine candidate protected animals against viral challenge 5 months following the last immunization. However, a combination protocol with ALVAC-env and two additional boosts of gp63 surprisingly failed to confer protection, suggesting that administration of the subunit preparation might be deleterious. Further, in the case of the NYVAC HTLV-Ienv recombinant, protection was afforded as early as 2 months following the first immunization. Last, all the protected animals in the NYVAC and ALVAC trials were challenged 5 months following the initial challenge exposure with 5 ml of blood from an HTLV-IBOU-infected animal, and subsequently became infected. Protection conferred by the attenuated HTLV-Ienv recombinant poxvirus vaccine in the rabbit model might be instrumental for optimizing the immunogenicity of poxvirus-based vaccine candidates against human immunodeficiency virus (HIV), particularly because of the need to enhance protection against cell-to-cell transmission.(ABSTRACT TRUNCATED AT 250 WORDS)
Franchini
G
G
Laboratory of Tumor Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Tartaglia
J
J
Markham
P
P
Benson
J
J
Fullen
J
J
Wills
M
M
Arp
J
J
Dekaban
G
G
Paoletti
E
E
Gallo
R C
RC
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology*; D015490:HTLV-I Infections / Q000517:prevention & control; D015368:Human T-lymphotropic virus 1 / Q000737:chemistry / Q000276:immunology / Q000302:isolation & purification*; D006801:Humans; D007109:Immunity; D008969:Molecular Sequence Data; D011817:Rabbits; D011994:Recombinant Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000821:virology*; D013997:Time Factors; D014611:Vaccination; D014614:Vaccines, Synthetic; D014765:Viral Vaccines
D017931:DNA Primers; D015686:Gene Products, env; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D014765:Viral Vaccines