Antibody-based concepts for multipurpose prevention technologies

Whaley, Kevin J.; Zeitlin, Larry

doi:10.1016/j.antiviral.2013.09.027

Cited by 12 publications

(8 citation statements)

References 66 publications

(73 reference statements)

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“…Since monoclonal antibodies (mAb) are far easier and cheaper to manufacture and characterize than pAb, we next investigated whether mAb against HSV-1 gD could immobilize the virions in CVM similarly to pAb 29 . We produced two variants of the same anti-gD IgG 1 mAb, one in mammalian cells (HSV8–293), and the other in tobacco plants i.e., Nicotiana benthamiana, engineered with human glycosylation pathways (HSV8-N) 30 .…”

Section: Resultsmentioning

confidence: 99%

Herpes simplex virus-binding IgG traps HSV in human cervicovaginal mucus across the menstrual cycle and diverse vaginal microbial composition

et al. 2018

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IgG possesses an important yet little recognized effector function in mucus. IgG bound to viral surface can immobilize otherwise readily diffusive viruses to the mucin matrix, excluding them from contacting target cells and facilitating their elimination by natural mucus clearance mechanisms. Cervicovaginal mucus (CVM) is populated by a microbial community, and its viscoelastic and barrier properties can vary substantially not only across the menstrual cycle, but also in women with distinct microbiota. How these variations impact the "muco-trapping" effector function of IgGs remains poorly understood. Here we obtained multiple fresh, undiluted CVM specimens (n = 82 unique specimens) from six women over time, and employed high-resolution multiple particle tracking to quantify the mobility of fluorescent Herpes Simplex Viruses (HSV-1) in CVM treated with different HSV-1-binding IgG. The IgG trapping potency was then correlated to the menstrual cycle, and the vaginal microbial composition was determined by 16 s rRNA. In the specimens studied, both polyclonal and monoclonal HSV-1-binding IgG appeared to consistently and effectively trap HSV-1 in CVM obtained at different times of the menstrual cycle and containing a diverse spectrum of commensals, including G. vaginalis-dominant microbiota. Our findings underscore the potential broad utility of this "muco-trapping" effector function of IgG to reinforce the vaginal mucosal defense, and motivates further investigation of passive immunization of the vagina as a strategy to protect against vaginally transmitted infections.

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Section: Resultsmentioning

confidence: 99%

Herpes simplex virus-binding IgG traps HSV in human cervicovaginal mucus across the menstrual cycle and diverse vaginal microbial composition

et al. 2018

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“…However, this drawback can be addressed by the use of higher doses, use of portable pumps for subcutaneous infusion (21), and genetic engineering of the antibody molecules, which can prolong antibody half life to 3 months (22). A vectored immunoprophylaxis approach can also circumvent the need for repeated injection of antibodies (23).…”

Section: Discussionmentioning

confidence: 99%

Commercially Available Immunoglobulins Contain Virus Neutralizing Antibodies Against All Major Genotypes of Polyomavirus BK

Randhawa

Pastrana

Zeng

et al. 2015

American Journal of Transplantation

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Neutralizing antibodies (NAbs) form the basis of immunotherapeutic strategies against many important human viral infections. Accordingly, we studied the prevalence, titer, genotype-specificity, and mechanism of action of anti-polyomavirus BK (BKV) NAbs in commercially available human immune globulin (IG) preparations designed for intravenous (IV) use. Pseudovirions (PsV) of genotypes Ia, Ib2, Ic, II, III, and IV were generated by co-transfecting a reporter plasmid encoding luciferase and expression plasmids containing synthetic codon-modified VP1, VP2, and VP3 capsid protein genes into 293TT cells. NAbs were measured using luminometry. All IG preparations neutralized all BKV genotypes, with mean EC50 titers as high as 254 899 for genotype Ia and 6,666 for genotype IV. Neutralizing titers against genotypes II and III were higher than expected, adding to growing evidence that infections with these genotypes are more common than currently appreciated. Batch to batch variation in different lots of IG was within the limits of experimental error. Antibody mediated virus neutralizing was dose dependent, modestly enhanced by complement, genotype-specific, and achieved without effect on viral aggregation, capsid morphology, elution, or host cell release. IG contains potent NAbs capable of neutralizing all major BKV genotypes. Clinical trials based on sound pharmacokinetic principles are needed to explore prophylactic and therapeutic applications of these anti-viral effects, until effective small molecule inhibitors of BKV replication can be developed.

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“…Alongside low MW chemical entities, different biopharmaceuticals have been shown to possess potent antiretroviral activity and some hold promise in developing vaginal microbicides [124][125]. Biopharmaceuticals include a wide range of molecules of biological origin that are usually obtained using biotechnological methods, namely proteins, peptides and genetic material.…”

Section: Other Microbicide Candidates and Strategiesmentioning

confidence: 99%

Polymer-based nanocarriers for vaginal drug delivery

Neves

Nunes

Machado

et al. 2015

Advanced Drug Delivery Reviews

113

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The vaginal delivery of various drugs is well described and its relevance established in current medical practice. Alongside recent advances and achievements in the fields of pharmaceutical nanotechnology and nanomedicine, there is an increasing interest in the potential use of different nanocarriers for the delivery of old and new pharmacologically active molecules with either therapeutic or prophylactic purposes. Nanosystems of polymeric nature in particular have been investigated over the last years and their interactions with mucosal fluids and tissues, as well as genital tract biodistribution upon vaginal administration, are now better understood. While different applications have been envisioned, most of the current research is focusing in the development of nano-formulations with the potential to inhibit the vaginal transmission of HIV upon sexual intercourse. The present work focuses its discussion on the potential and perils of polymer-based nanocarriers for the vaginal administration of different pharmacologically active molecules.

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Antibody-based concepts for multipurpose prevention technologies

Cited by 12 publications

References 66 publications

Herpes simplex virus-binding IgG traps HSV in human cervicovaginal mucus across the menstrual cycle and diverse vaginal microbial composition

Herpes simplex virus-binding IgG traps HSV in human cervicovaginal mucus across the menstrual cycle and diverse vaginal microbial composition

Commercially Available Immunoglobulins Contain Virus Neutralizing Antibodies Against All Major Genotypes of Polyomavirus BK

Polymer-based nanocarriers for vaginal drug delivery

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