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

J. F.L. Richmond, F. Mustafa, S. Lu, J. C. Santoro, J. Weng, M. O'Connell, E. M. Fenyö, J. L. Hurwitz, D. C. Montefiori, H. L. Robinson

Research output: Contribution to journalArticlepeer-review

57 Citations (Scopus)

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 108 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 patient 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 (~ 1:150 for MN) were raised in rabbits DNA primed with Envs from Swedish patient 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 Envs 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.

Original languageEnglish
Pages (from-to)265-274
Number of pages10
JournalVirology
Volume230
Issue number2
DOIs
Publication statusPublished - Apr 14 1997
Externally publishedYes

ASJC Scopus subject areas

  • Virology

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