The humoral response to HIV-1: new insights, renewed focus

Abstract

During the past 2 decades, significant advances in our understanding of the humoral immune response to human immunodeficiency virus type 1 (HIV-1) infection have been made, yet a tremendous amount of work lies ahead. Despite these advances, strategies to reliably induce antibodies that can control HIV-1 infection are still critically needed. However, recent advances in our understanding of the kinetics, specificity, and function of early humoral responses offer alternative new approaches to attain this goal. These results, along with the new broadly neutralizing antibody specificities, the role for other antibody functions, the increased understanding of HIV-1-induced changes to B cell biology, and results from the RV144 "Thai" trial showing potential modest sterilizing protection by nonneutralizing antibody responses, have renewed focus on the humoral system. In this review, recent advances in our understanding of the earliest humoral responses are discussed, highlighting presentations from the meeting on the Biology of Acute HIV Infection.

Figure 1

The antibody response to HIV-1 occurs in stages, shown here in a clockwise direction starting at the top. A. The initial antibody response to HIV-1 is non-neutralizing and directed at gp41. B. Soon thereafter arise non-neutralizing antibodies directed against gp120. C. After a delay of weeks to months, autologous neutralizing antibodies arise that apply selection pressure on the virus. D. Viral mutation results in neutralization escape by HIV-1, represented here by a change in the shape of gp120. E. In some patients, antibodies that can neutralize a wide range of HIV-1 isolates arise, represented here by a variety of shapes of gp120. Mixing of envelope shapes on a single virus particle is shown for illustrative purposes only.

Figure 2

Antibodies act as a bridge that can provide specificity and therefore focus the antiviral activity of innate immune cells to eliminate or contain viral replication following an interaction with an Fc-receptor located on the surface of an innate immune effector cell (including monocytes, NK cells, DCs, neutrophils, and other granulocytes).