Engineering Antibodies for the Treatment of Infectious Diseases

Fan, Gaowei; Li, Jinming

doi:10.1007/978-3-319-72077-7_10

Cited by 4 publications

(4 citation statements)

References 78 publications

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“…Due to the heterogeneity amongst the LcrV proteins from different isolates [ 30 , 75 ], the level of protection afforded by mAb 7.3 may drastically diminish if that specific epitope is altered; however, greater epitope coverage by polyclonal antibodies derived from Tc bovines may mitigate those possibilities. Additionally, novel antibody-based medical countermeasures will become increasingly more important strategies to combat anti-microbial resistance [ 76 , 77 , 78 ]. Drug-resistant isolates of Y. pestis have been isolated in several regions of Madagascar during relatively recent plague outbreaks and multi-drug resistant isolates continue to be of the utmost concern in both public health and biodefense arenas [ 79 , 80 ].…”

Section: Discussionmentioning

confidence: 99%

Polyclonal Antibodies Derived from Transchromosomic Bovines Vaccinated with the Recombinant F1-V Vaccine Increase Bacterial Opsonization In Vitro and Protect Mice from Pneumonic Plague

Biryukov

Dankmeyer

et al. 2023

Antibodies

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Plague is an ancient disease that continues to be of concern to both the public health and biodefense research communities. Pneumonic plague is caused by hematogenous spread of Yersinia pestis bacteria from a ruptured bubo to the lungs or by directly inhaling aerosolized bacteria. The fatality rate associated with pneumonic plague is significant unless effective antibiotic therapy is initiated soon after an early and accurate diagnosis is made. As with all bacterial pathogens, drug resistance is a primary concern when developing strategies to combat these Yersinia pestis infections in the future. While there has been significant progress in vaccine development, no FDA-approved vaccine strategy exists; thus, other medical countermeasures are needed. Antibody treatment has been shown to be effective in animal models of plague. We produced fully human polyclonal antibodies in transchromosomic bovines vaccinated with the recombinant F1-V plague vaccine. The resulting human antibodies opsonized Y. pestis bacteria in the presence of RAW264.7 cells and afforded significant protection to BALB/c mice after exposure to aerosolized Y. pestis. These data demonstrate the utility of this technology to produce large quantities of non-immunogenic anti-plague human antibodies to prevent or possibly treat pneumonic plague in human.

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Section: Discussionmentioning

confidence: 99%

Polyclonal Antibodies Derived from Transchromosomic Bovines Vaccinated with the Recombinant F1-V Vaccine Increase Bacterial Opsonization In Vitro and Protect Mice from Pneumonic Plague

Biryukov

Dankmeyer

et al. 2023

Antibodies

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“…Antibodies with fully human CDR3 regions isolated from transgenic animals represent a rapidly growing sector for antibody-based therapeutics 23 , 55 . The first antibody-based therapeutic derived from transgenic mice was approved by the FDA in 2006 for the treatment of metastatic colorectal cancer 56 .…”

Section: Discussionmentioning

confidence: 99%

“…In the 16 years since 19 mAbs have been approved including four generated in VelocImmune ® mice. Monoclonal antibodies with human Fab domains from transgenic mice have several advantages including the selection of high-affinity immunoglobulins, reduced production time, high-throughput methods for joining the variable regions to diverse human Fc domains, and implementation of diverse immunization strategies 23 , 55 . In this study, we generated a panel of broadly neutralizing anti-HCMV antibodies in VelocImmune ® mice that target the HCMV envelope protein gH.…”

Section: Discussionmentioning

confidence: 99%

Development of broadly neutralizing antibodies targeting the cytomegalovirus subdominant antigen gH

et al. 2022

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Human cytomegalovirus (HCMV) is a β-herpesvirus that increases morbidity and mortality in immunocompromised individuals including transplant recipients and newborns. New anti-HCMV therapies are an urgent medical need for diverse patient populations. HCMV infection of a broad range of host tissues is dependent on the gH/gL/gO trimer and gH/gL/UL28/UL130/UL131A pentamer complexes on the viral envelope. We sought to develop safe and effective therapeutics against HCMV by generating broadly-neutralizing, human monoclonal antibodies (mAbs) from VelocImmune® mice immunized with gH/gL cDNA. Following high-throughput binding and neutralization screening assays, 11 neutralizing antibodies were identified with unique CDR3 regions and a high-affinity (KD 1.4-65 nM) to the pentamer complex. The antibodies bound to distinct regions within Domains 1 and 2 of gH and effectively neutralized diverse clinical strains in physiologically relevant cell types including epithelial cells, trophoblasts, and monocytes. Importantly, combined adminstration of mAbs with ganciclovir, an FDA approved antiviral, greatly limited virus dissemination. Our work identifies several anti-gH/gL mAbs and sheds light on gH neutralizing epitopes that can guide future vaccine strategies.

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“…These therapies have safe profiles and are able to act as adjuncts to standard antimicrobial treatments. However, the immunity efficacies of immune-modulatory agents and antibodies remain low. , In addition, remarkable efforts have been made to develop novel safe and effective vaccines as preventive strategies against various infectious diseases. Nevertheless, antivirulence vaccination is usually applied toward a single antigen, which has an unsatisfactory effect on pathogenic species and strains that commonly secrete various broad-spectrum virulences …”

Section: Introductionmentioning

confidence: 99%

Cell Membrane-Coated Nanoparticles for Management of Infectious Diseases: A Review

Sun

Yang

et al. 2022

Ind. Eng. Chem. Res.

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Infectious diseases have emerged as leading threats to global healthcare, such as bacterial and viral infections. Major challenges in combating these infectious diseases are the emergence of adverse effects during the long-term use of anti-infectious drugs and the increasing prevalence of drug resistance. Cell membrane-coated nanoparticles have great potential in the prevention and therapy of infectious diseases. This promising therapeutic strategy is to employ cell membrane-based nanoparticles as a decoy to detain pathogenic microbes, a drug delivery platform, and an immunogenicity complex. Herein, the accelerating progression of biomimetic cell membrane-coated nanoparticles for the management of various infectious diseases is highlighted. We also discuss the challenges and the further application of cell membrane-coated nanoparticles in the view of clinical translation for combating infectious diseases. With a better understanding of the bioinspired camouflaged strategy, we anticipate that the use of cell membrane-coated nanoparticles will continue to grow and promote their applications in infectious diseases.

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Engineering Antibodies for the Treatment of Infectious Diseases

Cited by 4 publications

References 78 publications

Polyclonal Antibodies Derived from Transchromosomic Bovines Vaccinated with the Recombinant F1-V Vaccine Increase Bacterial Opsonization In Vitro and Protect Mice from Pneumonic Plague

Polyclonal Antibodies Derived from Transchromosomic Bovines Vaccinated with the Recombinant F1-V Vaccine Increase Bacterial Opsonization In Vitro and Protect Mice from Pneumonic Plague

Development of broadly neutralizing antibodies targeting the cytomegalovirus subdominant antigen gH

Cell Membrane-Coated Nanoparticles for Management of Infectious Diseases: A Review

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