Induction of inhibitory antibodies to the CCR5 chemokine receptor and their complementary role in preventing SIV infection in macaques

Lehner, Thomas; Wang, Yufei; Doyle, Carl; Tao, Louisa; Bergmeier, Lesley A.; Mitchell, Elaine; Bogers, Willy; Heeney, Jonathan L.; Kelly, Charles

doi:10.1002/(sici)1521-4141(199908)29:08<2427::aid-immu2427>3.3.co;2-x

Cited by 9 publications

(14 citation statements)

References 27 publications

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“…On the other hand, non-HIV-specific events could also contribute to the induction and modulation of anti-cell humoral immune responses towards membrane molecules that are involved in HIV docking and entry. Indeed, our results also show that anti-cell antibodies must be considered as predictive markers of HIV exposure (Ditzel et al, 1998;Lehner et al, 1992Lehner et al, , 1999Lopalco et al, 2000a).…”

Section: Discussionsupporting

confidence: 67%

Predictive value of anti-cell and anti-human immunodeficiency virus (HIV) humoral responses in HIV-1-exposed seronegative cohorts of European and Asian origin

Lopalco¹,

Barassi²,

Paolucci³

et al. 2005

Journal of General Virology

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Unconventional immune responses have been demonstrated in individuals who, despite repeated exposure to human immunodeficiency virus (HIV) infection, remain seronegative. As environmental exposure to pathogens and genetic background may modulate immune responses differentially, one Italian and two Asian populations of HIV-1-exposed seronegative individuals were studied. In serum samples from each group, IgG to CCR5, IgG to CD4 and IgA to gp41 were measured, which were previously described as markers of unconventional immunity in HIV-exposed seronegative Caucasians. Given the importance of conformational epitopes in virus-cell interactions, IgG to CD4-gp120 complex was also measured. It was found that markers of HIV exposure were present in all populations studied. HIV-specific humoral responses (IgA to gp41 and IgG to CD4-gp120 complex) were extremely significant predictors of HIV exposure (P<0?0001 in both cases), whereas the predictive values of anti-cell antibodies (anti-CCR5 and anti-CD4) varied between populations. Evidence is provided for the correlation of these differences with route of exposure to HIV and level of natural antibodies to cross-reactive microbial antigens. In conclusion, exposed seronegative individuals of ethnically different origins display similar signs of HIV-dependent unconventional immunity. A specific relevance must be attributed to different innate and acquired factors.

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Section: Discussionsupporting

confidence: 67%

Predictive value of anti-cell and anti-human immunodeficiency virus (HIV) humoral responses in HIV-1-exposed seronegative cohorts of European and Asian origin

Lopalco¹,

Barassi²,

Paolucci³

et al. 2005

Journal of General Virology

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“…In view of the antibodies elicited against CCR5 on xenoimmunization in macaques (Lehner et al, 1999) and alloimmunization in humans (Wang et al, 2002), we examined the possibility that mucosal alloimmunization might also induce antibodies to CCR5. A dose-dependent increase in the titre of IgG antibodies to CCR5 was found in the sera of alloimmunized macaques, which may enhance blocking of CCR5 by CD8 + cell-derived CC chemokines and SF, thereby preventing SIV infection.…”

Section: Discussionmentioning

confidence: 99%

Mucosal alloimmunization elicits T-cell proliferation, CC chemokines, CCR5 antibodies and inhibition of simian immunodeficiency virus infectivity

Bergmeier

Babaahmady

Wang

et al. 2005

Journal of General Virology

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The hypothesis was tested that mucosal stimulation with unmatched mononuclear cells would induce systemic alloimmune responses. Rectal or vaginal mucosal administration of 10 4-10 7 unmatched mononuclear cells induced significant dose-dependent T-cell proliferation stimulated by the allogeneic cells in rhesus macaques. This was associated with a significant upregulation of CD8 + T-cell-derived suppressor factor, as well as the CC chemokines CCL3, CCL4 and CCL5. In addition, there was a dose-dependent increase in antibodies to CCR5. These responses were associated with decreased in vitro simian immunodeficiency virus (SIV) infectivity of CD4 + T cells. A further investigation of SIV infectivity of CD4 + T cells separated from multiparous macaques also showed significant inhibition compared with male macaques. It is suggested that vaginal or rectal exposure to allogeneic stimulation by a partner's HLA antigens in seminal fluid, as occurs during sexual intercourse, or immunization by semi-allogeneic fetuses in multiparous females may elicit protection against SIV or human immunodeficiency virus infection.

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“…g each) in alum (x4) by the TILN (n = 6), nasorectal (n = 3) or i.d. route (n = 3), and two unimmunized macaques were challenged rectally with 9500 TCID 50 of cellfree SIVmac 251 J5 molecular clone; two macaques were not challenged (most of the series was described previously) [55]. Briefly, recombinant SIVmac 251 gp120 was expressed in recombinant baculovirus-infected cells [56], and SIV p27 was expressed in pGEX-3X as a glutathione S-transferase fusion protein.…”

Section: Immunization and Infectionmentioning

confidence: 99%

“…1, 2, 4, 5, 6) was immunized by the TILN route (x6) with 200 ? g HSP70 covalently linked to synthetic 20-mer peptides derived from the extracellular domains of CCR5 which was studied for the immunogenicity of these peptides [55]. An additional macaque (no.…”

Section: Immunization Of Rhesus Macaques With Hsp70 Linked To Synthetmentioning

confidence: 99%

The role of γ δ T cells in generating antiviral factors and β-chemokines in protection against mucosal simian immunodeficiency virus infection

et al. 2000

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In view of the role of γ δ+ T cells in mucosal protection against infection, the proportion of γ δ T cells was examined in cells eluted from lymphoid and mucosal tissues of macaques immunized with simian immunodeficiency virus (SIV) gp120 and p27 in alum and challenged with live SIV by the rectal mucosal route. This revealed a significant increase in γ δ T cells eluted from the rectal mucosa (p < 0.01) and the related iliac lymph nodes (p < 0.0001) in protected as compared with infected macaques. Preferential homing of PKH‐26‐labeled γ δ+ T cells from the primed iliac lymph nodes to the rectal and cervico‐vaginal mucosa was demonstrated after targeted iliac lymph node as compared with i. m. immunization. Investigations of the mechanism of protection revealed that γ δ+ T cells can generate antiviral factors, RANTES, macrophage inflammatory protein (MIP)‐1α and MIP‐1β which can prevent SIV infection by binding to the CCR5 coreceptors. Up‐regulation of γ δ+ T cells was demonstrated by immunization of macaques with heat shock protein (HSP)70 linked to peptides and with granulocyte‐macrophage colony‐stimulating factor (GM‐CSF). This was confirmed by in vitro studies showing that GM‐CSF can up‐regulate γ δ+ T cells from macaques immunized with HSP‐linked peptides but not those from naive animals. We suggest that a novel strategy of immunization with HSP70 linked to antigen may generate both cognate immunity to the antigen and innate immunity by virtue of up‐regulation of γ δ+ T cells. These cells generate antiviral factors and the three β‐chemokines that prevent binding and transmission of SIV or M‐tropic HIV by the CCR5 coreceptor.

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Induction of inhibitory antibodies to the CCR5 chemokine receptor and their complementary role in preventing SIV infection in macaques

Cited by 9 publications

References 27 publications

Predictive value of anti-cell and anti-human immunodeficiency virus (HIV) humoral responses in HIV-1-exposed seronegative cohorts of European and Asian origin

Predictive value of anti-cell and anti-human immunodeficiency virus (HIV) humoral responses in HIV-1-exposed seronegative cohorts of European and Asian origin

Mucosal alloimmunization elicits T-cell proliferation, CC chemokines, CCR5 antibodies and inhibition of simian immunodeficiency virus infectivity

The role of γ δ T cells in generating antiviral factors and β-chemokines in protection against mucosal simian immunodeficiency virus infection

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