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    Screening of HIV-1 Env glycoproteins for the ability to raise neutralizing antibody using DNA immunization and recombinant vaccinia virus boosting

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    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.
    UMass Chan Affiliations
    Department of Pathology
    Graduate School of Biomedical Sciences
    Document Type
    Journal Article
    Publication Date
    1997-04-14
    Keywords
    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 Virus
    Life Sciences
    Medicine and Health Sciences
    
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    Link to Full Text
    http://dx.doi.org/10.1006/viro.1997.8478
    Abstract
    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 site
    DOI
    10.1006/viro.1997.8478
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/32474
    PubMed ID
    9143282
    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1006/viro.1997.8478
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    Morningside Graduate School of Biomedical Sciences Scholarly Publications

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