Screening of HIV-1 Env glycoproteins for the ability to raise neutralizing antibody using DNA immunization and recombinant vaccinia virus boosting
Authors
Richmond, Joan F. L.Mustafa, Farah
Lu, Shan
Santoro, Joseph C.
Weng, Jiayu
O'Connell, Maryellen
Fenyo, Eva Maria
Hurwitz, Julia L.
Montefiori, David C.
Robinson, Harriet L.
Document Type
Journal ArticlePublication Date
1997-04-14Keywords
AIDS Vaccines; Animals; Biolistics; Cell Line, Transformed; Female; Gene Products, env; Genetic Vectors; HIV Antibodies; HIV Envelope Protein gp120; HIV-1; Humans; Immunization, Secondary; Neutralization Tests; Plasmids; Rabbits; T-Lymphocytes; Vaccines, DNA; Vaccines, Synthetic; Vaccinia virus; env Gene Products, Human Immunodeficiency VirusLife Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
HIV-1 envelopes from two series of primary isolates (from Swedish patients 5 and 6), from JR-FL and BaL (prototypic monocyte/macrophage tropic viruses) and from HXB-2 (a prototypic T-cell-line-adapted virus), have been screened for their ability to elicit neutralizing antibody to HIV-1. Rabbits were primed by gene gun inoculation with plasmids expressing secreted monomeric (gp120) and oligomeric (gp140) forms of each Env. After four to six DNA immunizations administered over a 1-year period, rabbits were boosted with 10(8) plaque-forming units of a mixture of seven recombinant vaccinia viruses which express chimeric gp140 Envs (primary clade B sequences in a IIIb-related BH10 backbone). Neutralizing antibodies were assayed against two T-cell-line-adapted viruses (MN and IIIb), two non-syncytium-inducing (NSI) and two syncytium-inducing (SI) primary isolates, and two HIV-1-NL4-3-recombinants with patients 5 or 6 Envs (NL4-3/5A, NL4-3/6C). The DNA priming and recombinant vaccinia virus boosting raised low titers of neutralizing antibody in 10 of 19 rabbits. The highest titers of neutralizing activity (approximately 1:150 for MN) were raised in rabbits DNA primed with Envs from Swedish patients 5. These sera cross neutralized IIIb and MN but did not neutralize the primary isolates or the NL4-3 recombinant with the homologous 5A Env. Sera from rabbits primed with the HXB-2 Env DNA were, for the most part, type-specific for neutralization of IIIb. In one of three assays, sera from rabbits primed with plasmids expressing the JR-FL and BaL had possible low titer neutralizing activity for two NSI, but not two SI, primary isolates. Our results highlight the low immunogenic potential of the HIV-1 Env and demonstrate that different Envs have different potentials to raise low titer neutralizing antibody.Source
Virology. 1997 Apr 14;230(2):265-74. Link to article on publisher's siteDOI
10.1006/viro.1997.8478Permanent Link to this Item
http://hdl.handle.net/20.500.14038/32474PubMed ID
9143282Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1006/viro.1997.8478