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Isotype Diversification of IgG Antibodies to HIV Gag Proteins as a Therapeutic Vaccination Strategy for HIV Infection.

French MA, Abudulai LN, Fernandez S - Vaccines (Basel) (2013)

Bottom Line: 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.These immune responses appear to include IgG antibodies to HIV-1 Gag proteins, interferon-a-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.

View Article: PubMed Central - PubMed

Affiliation: School of Pathology and Laboratory Medicine, University of Western Australia, Perth 6009, Australia. martyn.french@uwa.edu.au.

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-a-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.

No MeSH data available.


Related in: MedlinePlus

A diagrammatic representation of how isotype diversification of IgG antibodies against HIV-1 Gag proteins might enhance anti-viral accessory cell responses against HIV-1 infection. It is proposed that IgG antibodies bind to HIV-1 Gag proteins expressed on the surface of cells infected by HIV-1, including resting CD4+ T-cells [9]. Activation of natural killer (NK) cells is elicited by “downstream” IgG isotypes (IgG3 and IgG1) via FcγRIIIa. “Upstream” IgG isotypes (IgG2 and possibly IgG4) may also contribute to NK cell activation by ligating FcγRIIIa, particularly in individuals carrying the 158V genotype. However, it is proposed that multimeric IgG2 antibodies primarily broaden the function of the antibody response by enhancing phagocytic activity against Gag proteins associated with HIV-1 RNA, as a consequence of the functional characteristics of IgG2 (see Table 1), which activates plasmacytoid dendritic cells (pDCs) via FcγRIIa. Activation of pDCs leads to the production of IFN-α, which facilitates NK cell responses and induces the production of interferon-stimulated genes (ISGs) and to antigen presentation and/or stimulation of B- and T-cells (see text). HIV-1 infection impairs diversification of an IgG antibody response to “downstream” isotypes.
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vaccines-01-00328-f002: A diagrammatic representation of how isotype diversification of IgG antibodies against HIV-1 Gag proteins might enhance anti-viral accessory cell responses against HIV-1 infection. It is proposed that IgG antibodies bind to HIV-1 Gag proteins expressed on the surface of cells infected by HIV-1, including resting CD4+ T-cells [9]. Activation of natural killer (NK) cells is elicited by “downstream” IgG isotypes (IgG3 and IgG1) via FcγRIIIa. “Upstream” IgG isotypes (IgG2 and possibly IgG4) may also contribute to NK cell activation by ligating FcγRIIIa, particularly in individuals carrying the 158V genotype. However, it is proposed that multimeric IgG2 antibodies primarily broaden the function of the antibody response by enhancing phagocytic activity against Gag proteins associated with HIV-1 RNA, as a consequence of the functional characteristics of IgG2 (see Table 1), which activates plasmacytoid dendritic cells (pDCs) via FcγRIIa. Activation of pDCs leads to the production of IFN-α, which facilitates NK cell responses and induces the production of interferon-stimulated genes (ISGs) and to antigen presentation and/or stimulation of B- and T-cells (see text). HIV-1 infection impairs diversification of an IgG antibody response to “downstream” isotypes.

Mentions: 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 antibody response that facilitates the accessory cell responses of NK cells and pDCs to elicit both ADCC responses by NK cells, as well as phagocytosis of complexed antibody by pDCs and a pDC-dependant antiviral response (Figure 2). Further experimental evidence is required to strengthen our hypothesis. In particular, studies are needed to establish that IgG2 antibodies inhibit HIV-1 replication and are not just a marker of Th1 responses. However, at a time when new approaches to the development of HIV vaccines are needed [2], we suggest that consideration should be given to vaccination strategies that will enhance isotype diversification of IgG antibodies against HIV-1 Gag proteins.


Isotype Diversification of IgG Antibodies to HIV Gag Proteins as a Therapeutic Vaccination Strategy for HIV Infection.

French MA, Abudulai LN, Fernandez S - Vaccines (Basel) (2013)

A diagrammatic representation of how isotype diversification of IgG antibodies against HIV-1 Gag proteins might enhance anti-viral accessory cell responses against HIV-1 infection. It is proposed that IgG antibodies bind to HIV-1 Gag proteins expressed on the surface of cells infected by HIV-1, including resting CD4+ T-cells [9]. Activation of natural killer (NK) cells is elicited by “downstream” IgG isotypes (IgG3 and IgG1) via FcγRIIIa. “Upstream” IgG isotypes (IgG2 and possibly IgG4) may also contribute to NK cell activation by ligating FcγRIIIa, particularly in individuals carrying the 158V genotype. However, it is proposed that multimeric IgG2 antibodies primarily broaden the function of the antibody response by enhancing phagocytic activity against Gag proteins associated with HIV-1 RNA, as a consequence of the functional characteristics of IgG2 (see Table 1), which activates plasmacytoid dendritic cells (pDCs) via FcγRIIa. Activation of pDCs leads to the production of IFN-α, which facilitates NK cell responses and induces the production of interferon-stimulated genes (ISGs) and to antigen presentation and/or stimulation of B- and T-cells (see text). HIV-1 infection impairs diversification of an IgG antibody response to “downstream” isotypes.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494226&req=5

vaccines-01-00328-f002: A diagrammatic representation of how isotype diversification of IgG antibodies against HIV-1 Gag proteins might enhance anti-viral accessory cell responses against HIV-1 infection. It is proposed that IgG antibodies bind to HIV-1 Gag proteins expressed on the surface of cells infected by HIV-1, including resting CD4+ T-cells [9]. Activation of natural killer (NK) cells is elicited by “downstream” IgG isotypes (IgG3 and IgG1) via FcγRIIIa. “Upstream” IgG isotypes (IgG2 and possibly IgG4) may also contribute to NK cell activation by ligating FcγRIIIa, particularly in individuals carrying the 158V genotype. However, it is proposed that multimeric IgG2 antibodies primarily broaden the function of the antibody response by enhancing phagocytic activity against Gag proteins associated with HIV-1 RNA, as a consequence of the functional characteristics of IgG2 (see Table 1), which activates plasmacytoid dendritic cells (pDCs) via FcγRIIa. Activation of pDCs leads to the production of IFN-α, which facilitates NK cell responses and induces the production of interferon-stimulated genes (ISGs) and to antigen presentation and/or stimulation of B- and T-cells (see text). HIV-1 infection impairs diversification of an IgG antibody response to “downstream” isotypes.
Mentions: 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 antibody response that facilitates the accessory cell responses of NK cells and pDCs to elicit both ADCC responses by NK cells, as well as phagocytosis of complexed antibody by pDCs and a pDC-dependant antiviral response (Figure 2). Further experimental evidence is required to strengthen our hypothesis. In particular, studies are needed to establish that IgG2 antibodies inhibit HIV-1 replication and are not just a marker of Th1 responses. However, at a time when new approaches to the development of HIV vaccines are needed [2], we suggest that consideration should be given to vaccination strategies that will enhance isotype diversification of IgG antibodies against HIV-1 Gag proteins.

Bottom Line: 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.These immune responses appear to include IgG antibodies to HIV-1 Gag proteins, interferon-a-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.

View Article: PubMed Central - PubMed

Affiliation: School of Pathology and Laboratory Medicine, University of Western Australia, Perth 6009, Australia. martyn.french@uwa.edu.au.

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-a-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.

No MeSH data available.


Related in: MedlinePlus