| Autor: |
Kothe DL; Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA., Decker JM, Li Y, Weng Z, Bibollet-Ruche F, Zammit KP, Salazar MG, Chen Y, Salazar-Gonzalez JF, Moldoveanu Z, Mestecky J, Gao F, Haynes BF, Shaw GM, Muldoon M, Korber BT, Hahn BH |
| Jazyk: |
angličtina |
| Zdroj: |
Virology [Virology] 2007 Mar 30; Vol. 360 (1), pp. 218-34. Date of Electronic Publication: 2006 Nov 13. |
| DOI: |
10.1016/j.virol.2006.10.017 |
| Abstrakt: |
"Centralized" (ancestral and consensus) HIV-1 envelope immunogens induce broadly cross-reactive T cell responses in laboratory animals; however, their potential to elicit cross-reactive neutralizing antibodies has not been fully explored. Here, we report the construction of a panel of consensus subtype B (ConB) envelopes and compare their biologic, antigenic, and immunogenic properties to those of two wild-type Env controls from individuals with early and acute HIV-1 infection. Glycoprotein expressed from full-length (gp160), uncleaved (gp160-UNC), truncated (gp145), and N-linked glycosylation site deleted (gp160-201N/S) versions of the ConB env gene were packaged into virions and, except for the fusion defective gp160-UNC, mediated infection via the CCR5 co-receptor. Pseudovirions containing ConB Envs were sensitive to neutralization by patient plasma and monoclonal antibodies, indicating the preservation of neutralizing epitopes found in contemporary subtype B viruses. When used as DNA vaccines in guinea pigs, ConB and wild-type env immunogens induced appreciable binding, but overall only low level neutralizing antibodies. However, all four ConB immunogens were significantly more potent than one wild-type vaccine at eliciting neutralizing antibodies against a panel of tier 1 and tier 2 viruses, and ConB gp145 and gp160 were significantly more potent than both wild-type vaccines at inducing neutralizing antibodies against tier 1 viruses. Thus, consensus subtype B env immunogens appear to be at least as good as, and in some instances better than, wild-type B env immunogens at inducing a neutralizing antibody response, and are amenable to further improvement by specific gene modifications. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
Full Text from ScienceDirect