Identification and characterization of sera from HIV-infected individuals with broad cross-neutralizing activity against group M (env clade A–H) and group O primary HIV-1 isolates
✍ Scribed by Els Beirnaert; Phillipe Nyambi; Betty Willems; Leo Heyndrickx; Robert Colebunders; Wouter Janssens; Guido van der Groen
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- English
- Weight
- 206 KB
- Volume
- 62
- Category
- Article
- ISSN
- 0146-6615
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✦ Synopsis
A previous study on cross-clade neutralization activity, identified three key isolates, MNlab (envB/gagB; X4 coreceptor), VI525 (envG/gagH, envA/gagA; R5X4) and CA9 (Group O; R5), that allowed discrimination of sera, likely or unlikely to neutralize primary HIV-1 isolates belonging to Group M (env clades A-H) and Group O. The prognostic ability of these three isolates was verified by means of an external validation on a different and larger set of sera. A total of 79 different sera (66 HIV-1, 10 HIV-2, 1 HIV-1+2 and 2 SIV cpz ) were examined first for their capacity to neutralize the three key isolates, next sera were challenged against 12 other primary HIV-1 isolates of Group M (env A-H) and 2 isolates of Group O. Sera that neutralized all three isolates with an ID 50 titer of Ն1/40, also neutralized the 14 other primary isolates belonging to different genetic groups and clades. Sera that did not neutralize all three isolates did not exert broad cross-neutralizing activity. The neutralizing activity was antibody-mediated because it was absorbed and eluted from a Prot-G column. Competition-neutralization experiments using recombinant gp120 (HIV-1 MNlab) reduced the neutralizing capacity, suggesting that the neutralizing antibodies were directed against the Env protein. Remarkably, the broad crossneutralization activity was found primarily in African female patients. In conclusion, this study confirms that three isolates are sufficient to allow identification of broad cross-neutralizing sera.