Frequent intratype neutralization by plasma immunoglobulin a identified in HIV type 2 infection

Abstract

Human immunodeficiency virus type 2 (HIV-2) is less transmissible and less pathogenic compared to HIV-1 and, when matched for CD4(+) T cell count, the plasma viral load in HIV-2-infected individuals is approximately one log lower than in HIV-1-infected individuals. The explanation for these observations is elusive, but differences in virus controlling immunity generated in the two infections may be contributing factors. In the present study, we investigated neutralization by immunoglobulin A (IgA), in parallel with IgG, purified from plasma of HIV-1, HIV-2, and HIV-1/HIV-2 dually (HIV-D) infected individuals. Neutralization was analyzed against HIV-1 and HIV-2 isolates using a plaque reduction assay. In HIV-2 infection, intratype-specific neutralization by IgA was frequently detected, although at a lesser magnitude then the corresponding IgG neutralizing titers. In contrast, neutralization by IgA could rarely be demonstrated in HIV-1 infection despite similar plasma IgA levels in both infections. In addition, IgA and IgG of HIV-D plasma neutralized the HIV-2 isolate more potently than the HIV-1 isolate, suggesting that the difference between neutralizing activity of plasma IgA and IgG depends on the virus itself. Taken together, these findings suggest that both IgA and IgG add to the potent intratype neutralizing activity detected in HIV-2 plasma, which may contribute to virus control in HIV-2 infection.

FIG. 1.

Magnitude of intratype and intertype neutralization of HIV-1, HIV-2, and HIV-D plasma IgG and IgA. Median magnitude scores of intratype and intertype neutralization of HIV-1 (n=10), HIV-2 (n=10), and HIV-1/HIV-2 dually (HIV-D) (n=8) plasma IgG (A) and IgA (B) against HIV-1 and HIV-2 isolates. The diameters of circles correspond to the magnitude of neutralization of plasma IgG and IgA. Titer-based magnitudes of 0, 0.4, 0.5, 1.1, 2.1, 7.8, and 8.6 correspond to reciprocal titers of <40, 50, 60, 120, 335, 176,000, and 423,000, respectively. *p<0.05, **p<0.01, ***p<0.001.

FIG. 2.

Plasma IgG and IgA levels. The total amounts of IgG (A) and IgA (B) in plasma of HIV-1 (n=10), HIV-2 (n=10), HIV-1/HIV-2 dually (HIV-D) (n=8) infected, and HIV-negative (HIV-N) (n=16) individuals were quantified by ELISA. **p<0.01, ***p<0.001.

FIG. 3.

Intratype functionality of plasma IgG and IgA in HIV-1 and HIV-2 infections. Immunoglobulin functionality was calculated by dividing the highest reciprocal neutralizing titer of immunoglobulin by the corresponding plasma immunoglobulin level (mg) present in the assay. IgG and IgA titers where neutralization was not detected at 1:20 dilution were given a reciprocal titer of 10. Boxes illustrate interquartile range with median indicated and whiskers minimum and maximum. *p<0.05, ***p<0.001.