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.
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 > or =1/40, 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 cross-neutralization 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.
Department of Microbiology, Institute of Tropical Medicine, Antwerp, Belgium.
E
E
Beirnaert
P
P
Nyambi
B
B
Willems
L
L
Heyndrickx
R
R
Colebunders
W
W
Janssens
G
G
van der Groen
D015492:AIDS Serodiagnosis; D000818:Animals; D002460:Cell Line; D005260:Female; D005838:Genotype; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015658:HIV Infections / Q000175:diagnosis* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000276:immunology* / Q000302:isolation & purification; D015498:HIV-2 / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D009500:Neutralization Tests; D002679:Pan troglodytes; D010641:Phenotype; D011379:Prognosis; D015302:Simian Immunodeficiency Virus / Q000276:immunology / Q000302:isolation & purification
D015699:HIV Envelope Protein gp120