Biodistribution of neutralizing monoclonal antibodies IgG1 b12 and LALA in mucosal and lymphatic tissues of rhesus macaques

Hessell, A.J.; Epson, Erin; Moldt, Brian; Rakasz, Eva G.; Pandey, Shilpi; Sutton, WF; Brower, Zachary; Vm, Hirsch; Burton,; Haigwood, N. L.

doi:10.1186/1742-4690-9-s2-p204

Cited by 3 publications

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“…In 2012, the concentrations and kinetics of b12 and its LALA effector function deficient variant were assessed in adult female macaques. 129 The findings demonstrated that the rapid and broad distribution to lymphoid and mucosal tissues by both b12 and LALA were equivalent. Thus, the reduced protective capacity of LALA compared with b12 cannot be attributed to a differential effect of biodistribution.…”

Section: New Evidence Of Bnmab Activities In Tissuesmentioning

confidence: 87%

Use of broadly neutralizing antibodies for HIV‐1 prevention

Pegu¹,

Hessell

Mascola³

et al. 2017

Immunological Reviews

139

152

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Summary Antibodies have a long history in antiviral therapy, but until recently they have not been actively pursued for HIV-1 due to modest potency and breadth of early human monoclonal antibodies (MAbs) and perceived insurmountable technical, financial, and logistical hurdles. Recent advances in the identification and characterization of MAbs with the ability to potently neutralize diverse HIV-1 isolates has reinvigorated discussion and testing of these products in humans, since new broadly neutralizing MAbs (bnMAbs) are more likely to be effective against worldwide strains of HIV-1. In animal models, there is abundant evidence that bnMAbs can block infection in a dose dependent manner, and the more potent bnMAbs will allow clinical testing at infusion doses that are practically achievable. Moreover, recent advances in antibody engineering are providing further improvements in MAb potency, breadth and half-life. This review summarizes the current state of the field of bnMAb protection in animal models as well as a review of variables that are critical for antiviral activity. Several bnMAbs are currently in clinical testing, and we offer perspectives on their use as pre-exposure prophylaxis (PrEP), potential benefits beyond sterilizing immunity, and a discussion of future approaches to engineer novel molecules.

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Section: New Evidence Of Bnmab Activities In Tissuesmentioning

confidence: 87%

Use of broadly neutralizing antibodies for HIV‐1 prevention

Pegu¹,

Hessell

Mascola³

et al. 2017

Immunological Reviews

139

152

View full text Add to dashboard Cite

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HIV-1/SIV Humoral Responses in External Secretions

Tomaras

2019

CIR

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The protective function of mucosal HIV-1- or SIV-specific antibodies against viral infection has stimulated extensive studies of their Ig isotype association with differences in specificity and in effector functions. In contrast to many mucosally acquired microbial infections in which the humoral responses are dominated by induction of secretory IgA (S-IgA), HIV-1/SIV infections stimulate vigorous IgG responses in sera as well as in external secretions but low IgA virus-specific antibodies although the total levels of IgA in these fluids remain unaltered. The diminished or even absent IgA responses to HIV-1/SIV and to other mucosal antigens in external secretions and their replacement with IgG is likely to influence the functionality of mucosal barriers and eliminate antiinflammatory effector functions of IgA antibodies. Furthermore, the polymeric character of S-IgA with 4-8 antigen-binding sites, exquisite resistance to proteolysis and anti-inflammatory potential are of great advantage in mucosal protection. The markedly different effector functions of mucosal antibodies of IgG and IgA isotypes must be considered in the design of HIV-1 vaccines to stimulate S-IgA responses at sites of virus entry and IgG responses in the systemic compartment.

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Which Antibody Functions are Important for an HIV Vaccine?

Moog

2014

Front. Immunol.

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HIV antibody (Ab) functions capable of preventing mucosal cell-free or cell-to-cell HIV transmission are critical for the development of effective prophylactic and therapeutic vaccines. In addition to CD4+ T cells, other potential HIV-target cell types including antigen-presenting cells (APCs) (dendritic cells, macrophages) residing at mucosal sites are infected. Moreover, the interactions between APCs and HIV lead to HIV cell-to-cell transmission. Recently discovered broadly neutralizing antibodies (NAbs) are able to neutralize a broad spectrum of HIV strains, inhibit cell-to-cell transfer, and efficiently protect from infection in the experimentally challenged macaque model. However, the 31% protection observed in the RV144 vaccine trial in the absence of detectable NAbs in blood samples pointed to the possible role of additional Ab inhibitory functions. Increasing evidence suggests that IgG Fcγ receptor (FcγR)-mediated inhibition of Abs present at the mucosal site may play a role in protection against HIV mucosal transmission. Moreover, mucosal IgA Abs may be determinant in protection against HIV sexual transmission. Therefore, defining Ab inhibitory functions that could lead to protection is critical for further HIV vaccine design. Here, we review different inhibitory properties of HIV-specific Abs and discuss their potential role in protection against HIV sexual transmission.

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Biodistribution of neutralizing monoclonal antibodies IgG1 b12 and LALA in mucosal and lymphatic tissues of rhesus macaques

Cited by 3 publications

References 0 publications

Use of broadly neutralizing antibodies for HIV‐1 prevention

Use of broadly neutralizing antibodies for HIV‐1 prevention

HIV-1/SIV Humoral Responses in External Secretions

Which Antibody Functions are Important for an HIV Vaccine?

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