Cases such as these have led some to suggest that irreproducibility should carry with it greater consequences, such as a requirement for academic institutions to return some or all of the grant money used to fund studies that prove irreproducible ( Similarly, Prassas and Diamandis spent two years and $500,000 investigating CUZD1, a potential biomarker for pancreatic cancer, using an ELISA assay that turned out to recognize CA125 instead ( An estimated US$800 million are wasted annually on poorly performing antibodies and US$350 million are lost in biomedical research because published results cannot be replicated, with bad antibodies the likely culprit in many cases (įor example, several years of research from multiple laboratories suggested that erythropoietin activates the erythropoietin receptor (EpoR) in tumor cells a follow-up study, however, showed that only one of the four EpoR antibodies used in these studies detected EpoR and none of the four antibodies were suitable for immunohistochemistry (Įt al., 2006). The high failure rate of commercially available antibodies identified by Berglund and authors of similar studies is concerning because time and money are wasted. Failure rates among the 51 represented vendors ranged from 0 to 100%, suggesting that proper validation and quality control can allow vendors to provide high quality reagents. However, the study also points to the solution. This confirmed what many already knew to be true just because an antibody is commercially available does not ensure its quality. The Berglund study also highlights a second source of the antibody problem: commercially available antibodies have similar failure rates. As part of the Human Protein Atlas project, BerglundĮt al quantified their antibody production success rate 49% of their 9,000 internally generated antibodies failed validation ( Some proteins do not elicit a strong immune response, others are too immunogenic, and yet others share too much homology with non-target proteins to yield a highly specific antibody. Production of monoclonal and polyclonal antibodies relies on an animal’s immune response, which is unpredictable and can vary from animal to animal even when they have the same genetic background. One source of the antibody quality problem is that it is not easy to generate a high-performing antibody.
Even though antibodies are central to basic research as well as drug development and diagnostics, quality concerns remain high, and finding an antibody that works well for a specific application is a formidable challenge. An EDIII-specific antibody protected mice from lethal ZIKV infection, illustrating the potential for antibody-based therapy.Antibodies are widely used for applications that range from flow cytometry and immunohistochemistry to western blotting and ELISA. The most potent neutralizing antibodies were ZIKV-specific and targeted EDIII or quaternary epitopes on infectious virus. Memory T cells against NS1 or E proteins were poorly crossreactive, even in donors pre-exposed to DENV. In contrast, antibodies against E protein domain I/II (EDI/II) were cross-reactive and, while poorly neutralizing, potently enhanced ZIKV and DENV infection in vitro and lethally enhanced DENV disease in mice. Antibodies to NS1 were largely ZIKV-specific and were used to develop a serological diagnostic tool. By characterizing memory cells from ZIKV-infected patients, we dissected ZIKV-specific and DENV-crossreactive immune responses. SUMMARY/ABSTRACT: Zika virus (ZIKV), a mosquito-borne flavivirus with homology to Dengue virus (DENV), has become a public health emergency. Specificity, cross-reactivity and function of antibodies elicited by Zika virus infection. REFERENCE: Stettler K, Beltramello M, Espinosa DA, et al.
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