Rapid evolution of the neutralizing antibody response to HIV type 1 infection - PubMed (original) (raw)

Rapid evolution of the neutralizing antibody response to HIV type 1 infection

Douglas D Richman et al. Proc Natl Acad Sci U S A. 2003.

Abstract

A recombinant virus assay was used to characterize in detail neutralizing antibody responses directed at circulating autologous HIV in plasma. Examining serial plasma specimens in a matrix format, most patients with primary HIV infection rapidly generated significant neutralizing antibody responses to early (0-39 months) autologous viruses, whereas responses to laboratory and heterologous primary strains were often lower and delayed. Plasma virus continually and rapidly evolved to escape neutralization, indicating that neutralizing antibody exerts a level of selective pressure that has been underappreciated based on earlier, less comprehensive characterizations. These data argue that neutralizing antibody responses account for the extensive variation in the envelope gene that is observed in the early months after primary HIV infection.

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Figures

Figure 1

Figure 1

(A) Diagrams of the expression vectors used to generate the pseudovirions used in the neutralization assay. The envelope-defective, luciferase-expressing vector is above the vector that expresses the full-length envelopes amplified from patient plasmas. (B) Schema of the generation of pseudovirions by cotransfection of the two vectors depicted in A. These pseudovirions then are incubated for 1 h with serial 4-fold dilutions of plasma or antibody solutions before infection of the U87-derived target cells to generate luciferase activity.

Figure 2

Figure 2

Neutralization of autologous HIV. The neutralizing activity of plasmas obtained from patient 1 at months 0, 6, and 12 after presentation with primary infection is assayed against virus from months 0 and 12. The titer is defined as the reciprocal of the dilution of plasma that produces 50% inhibition of virus replication (dashed lines). The error at each dilution reflects the standard error of duplicate wells.

Figure 3

Figure 3

Plasma HIV viral load in patient TE-1, who initiated potent antiretroviral therapy 16 weeks after presentation (see Table 7). The plasma HIV RNA values over time are shown.

Figure 4

Figure 4

Variable individual autologous neutralizing responses. The autologous neutralizing antibody responses are displayed for seven primary HIV infection patients who declined antiretroviral therapy and for five patients who initiated potent suppressive therapy within 3 months of seroconversion.

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