HIV-1-specific antibody responses during acute and chronic HIV-1 infection

Abstract

Purpose of review: The humoral immune response to HIV-1 throughout infection is comprised of complex mixtures of antibody isotypes with numerous HIV-1 specificities. However, unlike antibody responses to most infections, protective antibody responses are delayed and do not arise until long after HIV-1 latency is established. We review recent data on HIV-1-specific antibody isotypes induced following HIV-1 transmission: to understand the effects of HIV-1 on B cell and T cell effector responses, to understand the timing of the rise and fall of different anti-HIV-1 antibodies and to understand how antibodies could contribute to protective immunity if they were either pre-existing or elicited immediately after HIV-1 transmission.

Recent findings: Studies of the earliest events following infection by the transmitted/founder virus have recently revealed that early destruction of B cell generative microenvironments may be responsible for delay of potentially protective anti-HIV-1 antibody responses. Unlike the initial CD8 T cell response to HIV-1, the initial induced antibody response is usually ineffective in controlling virus replication during acute HIV-1 infection.

Summary: The antibody isotypes and specificities elicited during HIV-1 infection can provide a window into deciphering the detrimental effects of HIV-1 on B cell and T cell responses. Additionally, further characterization of the virus inhibitory capabilities of anti-HIV-1 antibody isotypes can define the spectrum of potential protective HIV-1 antibodies that could be readily elicited by experimental vaccines and adjuvants.

Figure 1. Sequentially elicited IgG antibodies to HIV-1 envelope epitopes

After HIV-1 transmission, antibody isotypes and specificities to the HIV-1 envelope are elicited sequentially [gp41, gp120, CD4bs, MPER (non-neutralizing), autologous neutralizing antibodies]. The first free HIV-1-specific antibody detected in the plasma is anti-gp41 IgM (red line). The immunodominant epitope is one of the known regions in gp41 recognized initially. Anti-gp41 IgM undergoes class switching to IgG and IgA, making gp41 the first protein also recognized by IgG and IgA antibodies. This figure shows the initial IgG response [6] to gp41 (green), gp120 (purple), CD4bs (dark blue), MPER (non-neutralizing) (light blue) through the development of autologous neutralizing antibodies (orange line) [7,8] within the first 3 months from transmission. The dotted line indicates when either plasma viremia or HIV-1-specific antibody is detectable in plasma. T₀ is the time at which plasma viremia reaches 100 copies/ml [6,9].