Abstract
The development of vaccines to treat and prevent human immunodeficiency virus (HIV) infection has been hampered by an incomplete understanding of “protective” immune responses against HIV. Natural control of HIV-1 infection is associated with T-cell responses against HIV-1 Gag proteins, particularly CD8+ T-cell responses restricted by “protective” HLA-B alleles, but other immune responses also contribute to immune control. These immune responses appear to include IgG antibodies to HIV-1 Gag proteins, interferon-α-dependant natural killer (NK) cell responses and plasmacytoid dendritic cell (pDC) responses. Here, it is proposed that isotype diversification of IgG antibodies against HIV-1 Gag proteins, to include IgG2, as well as IgG3 and IgG1 antibodies, will broaden the function of the antibody response and facilitate accessory cell responses against HIV-1 by NK cells and pDCs. We suggest that this should be investigated as a vaccination strategy for HIV-1 infection.
Highlights
The development of human immunodeficiency virus (HIV) vaccines is a global health priority, at a time when therapeutic vaccines are being considered as a component of a strategy for eradicating HIV infection [1]
The number of patients was small, this study provided evidence that the vaccine construct containing the gene for IFN- increased IgG antibodies to HIV p24, including IgG2 antibodies, which were associated with better control of HIV replication after antiretroviral therapy (ART) was ceased in patients who possessed the 131H genotype of Fc RIIa, which results in the highest affinity binding of IgG2 antibodies to that receptor
We propose that enhancing isotype diversification of IgG antibody responses against HIV-1 Gag proteins during vaccination, to include IgG2, as well as IgG3 and IgG1 antibodies, may result in an IgG
Summary
The development of human immunodeficiency virus (HIV) vaccines is a global health priority, at a time when therapeutic vaccines are being considered as a component of a strategy for eradicating HIV infection [1]. One third of HIV-1 controllers do not exhibit evidence of HLA-B-restricted CD8+ T-cell responses against Gag proteins [12], suggesting that other immune responses contribute to natural control of HIV-1 infection. An increasing amount of evidence indicates that natural control of HIV-1 infection is associated with responses by interferon (IFN)- -dependant natural killer (NK) cells [31] and plasmacytoid dendritic cells (pDCs) [32,33], which are the major producers of IFN- [34] Both NK cells and pDCs mediate innate immune responses against viruses [34,35], but both function as accessory cells in. Plasmacytoid dendritic cells function as antigen-presenting cells for T-cells [36,37,38,39], including cross-presentation to CD8+ T-cells [40,41], and regulate B-cell differentiation [42]
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