Dichotomy in cross-clade reactivity and neutralization by HIV-1 sera: Implications for active and passive immunotherapy.
The identification of broadly reactive and cross-clade neutralizing antibodies will facilitate the development of a more universally effective vaccine for human immunodeficiency virus (HIV). Antibodies in sera from individuals infected with Clade B HIV bind native primary viral isolates, and virus binding correlates with neutralization and stable clinical disease. In this study, we quantified cross-clade antibody reactivity and neutralization by Clades B and C sera. Primary viral isolates were captured by serum IgG bound to anti-human IgG and quantitated as p24 released by lysis of captured virus. Neutralization was determined using PHA-stimulated PBMC. Clade B antibodies reacted more frequently with Clade B R5 virus, but positive sera captured quantitatively more X4 virus than R5 and R5X4 virus. Clade B sera reacted less frequently and captured less Clade C virus than Clade B virus. Antibodies in Clade C sera captured Clades B and C isolates with equal frequency and quantity. There was no difference in neutralization of Clade B virus by either group of sera; however, Clade C sera neutralized Clade C virus, whereas Clade B sera were ineffective against Clade C virus. Thus, there are distinct differences in cross-clade reactivity of and neutralization by antibodies induced in response to Clade C infection compared to Clade B infection. Understanding antibody responses to native virions after Clade C infection and cross clade antibody behavior has implications for understanding pathogenesis and vaccine development.
Cavacini
Lisa A
LA
Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. lcavacin@bidmc.harvard.edu
Duval
Mark
M
Patil
Ajay
A
Wood
Charles
C
Mayer
Kenneth H
KH
Ruprecht
Ruth M
RM
Posner
Marshall R
MR
D016915:AIDS Vaccines; D003429:Cross Reactions; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000628:therapy; D015497:HIV-1 / Q000145:classification / Q000276:immunology*; D006801:Humans; D007116:Immunization, Passive; D009500:Neutralization Tests
D016915:AIDS Vaccines; D015483:HIV Antibodies