Reflection on passive immunotherapy in those who need most: some novel strategic arguments for obtaining safer therapeutic plasma or autologous antibodies from recovered COVID‐19 infected patients

AbstractOne of the main pathological hallmarks of Alzheimer’s disease (AD) is the intraneuronal accumulation of hyperphosphorylated tau. Passive immunotherapy is a promising strategy for the treatment of AD and there are currently a number of tau-specific monoclonal antibodies in clinical trials. A proposed mechanism of action is to engage and clear extracellular, pathogenic forms of tau. This process has been shown in vitro to be facilitated by microglial phagocytosis through interactions between the antibody-tau complex and microglial Fc-receptors. As this interaction is mediated by the conformation of the antibody's Fc domain, this suggests that the antibody isotype may affect the microglial phagocytosis and clearance of tau, and hence, the overall efficacy of tau antibodies. We therefore aimed to directly compare the efficacy of the tau-specific antibody, RN2N, cloned into a murine IgG1/κ framework, which has low affinity Fc-receptor binding, to that cloned into a murine IgG2a/κ framework, which has high affinity Fc-receptor binding. Our results demonstrate, for RN2N, that although enhanced microglial activation via the IgG2a/κ isotype increased extracellular tau phagocytosis in vitro, the IgG1/κ isoform demonstrated enhanced ability to reduce tau pathology and microgliosis following passive immunisation of the P301L tau transgenic pR5 mouse model.

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Possible Future Monoclonal Antibody (mAb)-Based Therapy against Arbovirus Infections

BioMed Research International ◽

10.1155/2013/838491 ◽

2013 ◽

Vol 2013 ◽

pp. 1-21 ◽

Cited By ~ 12

Author(s):

Giuseppe Sautto ◽

Nicasio Mancini ◽

Giacomo Gorini ◽

Massimo Clementi ◽

Roberto Burioni

Keyword(s):

Monoclonal Antibody ◽

Monoclonal Antibodies ◽

Side Effects ◽

Antiviral Activity ◽

The Other ◽

Viral Escape ◽

Passive Immunotherapy ◽

Medical Need

More than 150 arboviruses belonging to different families are known to infect humans, causing endemic infections as well as epidemic outbreaks. Effective vaccines to limit the occurrence of some of these infections have been licensed, while for the others several new immunogens are under development mostly for their improvements concerning safety and effectiveness profiles. On the other hand, specific and effective antiviral drugs are not yet available, posing an urgent medical need in particular for emergency cases. Neutralizing monoclonal antibodies (mAbs) have been demonstrated to be effective in the treatment of several infectious diseases as well as in preliminaryin vitroandin vivomodels of arbovirus-related infections. Given their specific antiviral activity as well-tolerated molecules with limited side effects, mAbs could represent a new therapeutic approach for the development of an effective treatment, as well as useful tools in the study of the host-virus interplay and in the development of more effective immunogens. However, before their use as candidate therapeutics, possible hurdles (e.g., Ab-dependent enhancement of infection, occurrence of viral escape variants) must be carefully evaluated. In this review are described the main arboviruses infecting humans and candidate mAbs to be possibly used in a future passive immunotherapy.

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Passive Immunotherapy of Mice Bearing Ehrlich Ascites Tumor Expressing Human, Membrane-Bound Placental Alkaline Phosphatase

Tumor Biology ◽

10.1159/000030121 ◽

2000 ◽

Vol 21 (3) ◽

pp. 145-152 ◽

Cited By ~ 1

Author(s):

Tibor Barka ◽

Scott Henderson ◽

Hendrika M. van der Noen

Keyword(s):

Alkaline Phosphatase ◽

Ehrlich Ascites Tumor ◽

Placental Alkaline Phosphatase ◽

Ascites Tumor ◽

Passive Immunotherapy ◽

Ehrlich Ascites ◽

Membrane Bound

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Egg Yolk Antibody Farming for Passive Immunotherapy

Functional Foods and Biotechnology ◽

10.1201/9781420007725-21 ◽

2006 ◽

pp. 401-420

Keyword(s):

Egg Yolk ◽

Passive Immunotherapy ◽

Egg Yolk Antibody

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Vaccination of COVID-19 Convalescent Plasma Donors Increases Binding and Neutralizing Antibodies Against SARS-CoV-2 Variants

10.1101/2021.10.28.21265622 ◽

2021 ◽

Author(s):

Clara Di Germanio ◽

Graham Simmons ◽

Chloe Thorbrogger ◽

Rachel Martinelli ◽

Mars Stone ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Passive Immunotherapy ◽

Post Vaccination ◽

Vaccination Rates ◽

Beneficial Effects ◽

Paired Samples ◽

Igg Binding ◽

The Us ◽

Before And After ◽

The Individual

Background: COVID-19 convalescent plasma (CCP) was widely used as passive immunotherapy during the first waves of SARS-CoV-2 infection in the US. However, based on observational studies and randomized controlled trials, beneficial effects of CCP were limited, and its use was virtually discontinued early in 2021, in concurrence with increased vaccination rates and availability of monoclonal antibody (mAb) therapeutics. However, as new variants of the SARS-CoV-2 spread, interest in CCP derived from vaccine-boosted CCP donors is resurging. The effect of vaccination of previously infected CCP donors on antibodies against rapidly spreading variants of concern (VOC) is still under investigation. Study Design/Methods: In this study, paired samples from 11 CCP donors collected before and after vaccination were tested to measure binding antibodies levels and neutralization activity against the ancestral and SARS-CoV-2 variants (Wuhan-Hu-1, B.1.1.7, B.1.351, P.1, D614G, B.1.617.2, B.1.427) on the Ortho Vitros Spike Total Ig and IgG assays, the MSD V-PLEX SARS-CoV-2 Panel 6 arrays for IgG binding and ACE2 inhibition, and variant-specific Spike Reporter Viral Particle Neutralization (RVPN) assays. Results/Findings: Binding and neutralizing antibodies were significantly boosted by vaccination, with several logs higher neutralization for all the variants tested post-vaccination compared to the pre-vaccination samples, with no difference found among the individual variants. Discussion: Vaccination of previously infected individuals boosts antibodies including neutralizing activity against all SARS-CoV-2 VOC, including the current spreading delta (B.1.617.2) variant. Animal model and human studies to assess clinical efficacy of vaccine boosted CCP are warranted, especially since 15-20% of current donations in the US are from previously infected vaccine-boosted donors.

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