TY - JOUR
T1 - Screening of HIV-1 Env glycoproteins for the ability to raise neutralizing antibody using DNA immunization and recombinant vaccinia virus boosting
AU - Richmond, J. F.L.
AU - Mustafa, F.
AU - Lu, S.
AU - Santoro, J. C.
AU - Weng, J.
AU - O'Connell, M.
AU - Fenyö, E. M.
AU - Hurwitz, J. L.
AU - Montefiori, D. C.
AU - Robinson, H. L.
N1 - Funding Information:
We are indebted to Drs. B. Cullen and I. Chen for the provision of pBaLc and pSVDFL112-1 plasmids, respectively. We thank Drs. J. Mul-lins and J. Haynes for their gifts of pJW4303 and pWR61602, respec- tively. We thank Drs. P. Earl, C. Broder, and B. Moss for vCB-14. We thank Dr. S. Zolla-Pazner for conducting neutralization assays for BZ167. This work was supported by U.S. Public Health Service Research Grant R01 AI 34241 (H. Robinson), by a Howard Hughes Postdoctoral Research Fellowship for Physicians (S. Lu), by 5-T32 AI 07272-12 (J. Richmond), by NIAID Contract NCI-6S-1649 (D. C. Montefiori), and by NCI Grant R01-CA57419, Cancer Center Support Core Grant P30-CA21765, and the American Lebanese Syrian Associated Charities (J. L. Hurwitz).
PY - 1997/4/14
Y1 - 1997/4/14
N2 - 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.
AB - 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.
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U2 - 10.1006/viro.1997.8478
DO - 10.1006/viro.1997.8478
M3 - Article
C2 - 9143282
AN - SCOPUS:0030917744
SN - 0042-6822
VL - 230
SP - 265
EP - 274
JO - Virology
JF - Virology
IS - 2
ER -