A Bispecific Antibody Composed of a Nonneutralizing Antibody to the gp41 Immunodominant Region and an Anti-CD89 Antibody Directs Broad Human Immunodeficiency Virus Destruction by Neutrophils

Duval, Mark; Posner, Marshall R.; Cavacini, Lisa A.

doi:10.1128/jvi.02499-07

Cited by 30 publications

(32 citation statements)

References 37 publications

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“…27,28 In addition to the role of IgG, several studies have also reported the importance of IgA against HIV. IgA has proven to be functional in protecting against HIV infection by direct neutralization, 29 -34 by inhibiting transcytosis of HIV across the mucosa, 29,31,35 -40 by intracellular virus neutralization, 41,42 and by preventing HIV entry past the epithelial lumen.…”

Section: Introductionmentioning

confidence: 99%

The gp41 epitope, QARVLAVERY, is highly conserved and a potent inducer of IgA that neutralizes HIV-1 and inhibits viral transcytosis

Jain

Rosenthal

2011

Mucosal Immunology

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Mucosal surfaces are the predominant site of human immunodeficiency virus (HIV)-1 transmission. For prophylactic approaches to effectively prevent HIV infection and subsequent dissemination, the induction of mucosally relevant protective immunity will be critical. Here, we have characterized the antibody (Ab) response generated by a highly conserved gp41epitope, QARVLAVERY, in an optimized immunization model that elicits potent epitope-specific Abs in the serum, vaginal washes, and fecal secretions of immunized mice. Our results show that QARVLAVERY is indeed a potent inducer of IgA and importantly, QARVLAVERY-specific IgA was effective in neutralizing HIV and inhibiting viral transcytosis. Intriguingly, QARVLAVERY also generated an approximate 1:1 ratio of IgG:IgA in the serum of immunized mice, independent of the delivery regimen and produced early systemic IgA, even before IgG. In light of the significantly high IgA induction by QARVLAVERY and the functionality of epitope-specific Abs in the inhibition of HIV infection and transcytosis, QARVLAVERY is an attractive epitope to be considered in mucosal vaccination strategies against HIV.

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Section: Introductionmentioning

confidence: 99%

The gp41 epitope, QARVLAVERY, is highly conserved and a potent inducer of IgA that neutralizes HIV-1 and inhibits viral transcytosis

Jain

Rosenthal

2011

Mucosal Immunology

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“…170 However, it was recently demonstrated that targeting Fc RI directed neutrophils to destroy HIV-infected target cells. 171 Because M. mulatta monkeys express Fc RI, an active role for Fc RI in eliciting protection is suggested, in addition to HIV neutralizing IgA Ab. Treatment of human Fc RI transgenic mice with specific IgA induced enhanced protection against B. pertussis or M. tuberculosis infection, compared with non-transgenic littermates.…”

Section: Targeting Fc Ri For Treatment Of Infectious Diseases and Cancermentioning

confidence: 99%

The human immunoglobulin A Fc receptor FcαRI: a multifaceted regulator of mucosal immunity

2011

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Immunoglobulin A (IgA) is commonly recognized as the most prevalent antibody (Ab) at mucosal sites with an important role in defense by shielding mucosal surfaces from invasion by pathogens. However, its potential to both actively dampen excessive immune responses or to initiate potent proinflammatory cellular processes is less well known. Interestingly, either functional outcome is mediated through interaction with the myeloid IgA Fc receptor FcαRI (CD89). Monomeric interaction of IgA with FcαRI triggers inhibitory signals that block activation via other receptors, whereas multimeric FcαRI crosslinking induces phagocytosis, reactive oxygen species production, antigen presentation, Ab-dependent cellular cytotoxicity, and cytokine release. Thus, FcαRI acts as a regulator between anti- and proinflammatory responses of IgA. As such, the biology of FcαRI, and its multifaceted role in immunity will be the focus of this review.

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“…Resident macrophages in the GI tract typically downregulate Fc receptors (60), but locally synthesized anti-Env IgA antibodies could mediate phagocytosis of SIV virions by FcR␣ ϩ neutrophils, monocytes, and dendritic cells recruited to infected tissues. Finally, HIV-specific IgA has been shown to be capable of mediating ADCC in the presence of blood monocytes (61), and it is likely that nonneutralizing IgA and neutrophils can also mediate this activity (62).…”

Section: Figmentioning

confidence: 99%

Vaccine-Elicited Mucosal and Systemic Antibody Responses Are Associated with Reduced Simian Immunodeficiency Viremia in Infant Rhesus Macaques

Jensen

Nabi

Rompay

et al. 2016

J Virol

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Despite significant progress in reducing peripartum mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV)with antiretroviral therapy (ART), continued access to ART throughout the breastfeeding period is still a limiting factor, and breast milk exposure to HIV accounts for up to 44% of MTCT. As abstinence from breastfeeding is not recommended, alternative means are needed to prevent MTCT of HIV. We have previously shown that oral vaccination at birth with live attenuated Mycobacterium tuberculosis strains expressing simian immunodeficiency virus (SIV) genes safely induces persistent SIV-specific cellular and humoral immune responses both systemically and at the oral and intestinal mucosa. Here, we tested the ability of oral M. tuberculosis vaccine strains expressing SIV Env and Gag proteins, followed by systemic heterologous (MVA-SIV Env/Gag/Pol) boosting, to protect neonatal macaques against oral SIV challenge. While vaccination did not protect infant macaques against oral SIV acquisition, a subset of immunized animals had significantly lower peak viremia which inversely correlated with prechallenge SIV Env-specific salivary and intestinal IgA responses and higher-avidity SIV Env-specific IgG in plasma. These controller animals also maintained CD4؉ T cell populations better and showed reduced tissue pathology compared to noncontroller animals. We show that infants vaccinated at birth can

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A Bispecific Antibody Composed of a Nonneutralizing Antibody to the gp41 Immunodominant Region and an Anti-CD89 Antibody Directs Broad Human Immunodeficiency Virus Destruction by Neutrophils

Cited by 30 publications

References 37 publications

The gp41 epitope, QARVLAVERY, is highly conserved and a potent inducer of IgA that neutralizes HIV-1 and inhibits viral transcytosis

The gp41 epitope, QARVLAVERY, is highly conserved and a potent inducer of IgA that neutralizes HIV-1 and inhibits viral transcytosis

The human immunoglobulin A Fc receptor FcαRI: a multifaceted regulator of mucosal immunity

Vaccine-Elicited Mucosal and Systemic Antibody Responses Are Associated with Reduced Simian Immunodeficiency Viremia in Infant Rhesus Macaques

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