Dis. 11:916C924 [PMC free article] [PubMed] [Google Scholar] 17. 2.3.2.1 and completely protected mice against lethal challenges of H5N1 viruses from clades 1 and 2.3.4. HA-7 specifically targeted the globular head of the H5N1 virus hemagglutinin (HA). Using electron microscopy technology with three-dimensional reconstruction (3D-EM), we discovered that HA-7 bound to a novel and highly conserved conformational epitope that CHMFL-ABL-121 was centered on residues 81 to 83 and 117 to 122 of HA1 (H5 numbering). We further demonstrated that HA-7 inhibited viral entry during postattachment events but not at the receptor-binding step, which is fully consistent with the 3D-EM result. Taken together, we propose that HA-7 could be humanized as an effective passive immunotherapeutic agent for antiviral stockpiling for future influenza pandemics caused by emerging unpredictable H5N1 strains. Our study also provides a sound foundation for the rational design of vaccines capable of inducing broad-spectrum immunity against H5N1. INTRODUCTION Mouse monoclonal to CD2.This recognizes a 50KDa lymphocyte surface antigen which is expressed on all peripheral blood T lymphocytes,the majority of lymphocytes and malignant cells of T cell origin, including T ALL cells. Normal B lymphocytes, monocytes or granulocytes do not express surface CD2 antigen, neither do common ALL cells. CD2 antigen has been characterised as the receptor for sheep erythrocytes. This CD2 monoclonal inhibits E rosette formation. CD2 antigen also functions as the receptor for the CD58 antigen(LFA-3) The unabated circulation of the highly pathogenic avian influenza A virus (IAV)/H5N1 continues to be a serious threat to public health worldwide. The transmission of H5N1 virus among humans has been rare, and no human pandemic has ever occurred as a result of this virus. Nonetheless, the first human case was reported to the WHO in 2003, and since then, there have been 608 documented human H5N1 cases with 359 deaths as of 10 August 2012, with a mortality rate approaching 60% (http://www.who.int/influenza/human_animal_interface/EN_GIP_20120810CumulativeNumberH5N1cases.pdf). Because of the high frequency of naturally occurring mutations, the lethality of H5N1 has raised great concerns about the potential transmissibility of the virus in humans. Recently, two research groups have made significant strides in the efficient transmission of the laboratory-mutated or reassortant H5N1 virus among mammals, particularly ferrets, which is the best animal model for humans. Introducing mutations in H5N1, or creating a reassortant of H5N1 and H1N1 viruses causing the 2009 2009 flu pandemic, makes it possible for the manipulated H5N1 virus to replicate efficiently in these animals (1C4). These results represent significant breakthroughs in identifying specific determinants of H5N1 transmission in ferrets but also stirred a months-long debate on global biosecurity- and biosafety-related issues (5C8). Therefore, there is a strong need to explore effective strategies to combat influenza pandemics caused by H5N1 viruses in the future. To efficiently prevent a future influenza pandemic, a robust global surveillance system should be in place for the timely detection of novel H5N1 virus strains in animals once they arise. Such a coordinated surveillance and control effort has not always been successful (9). On the other hand, inactivated virus vaccines and live-attenuated, cold-adapted H5N1 vaccines could also be developed for the prevention of H5N1 virus infection via large-scale vaccination (10C12). Other forms of H5N1 vaccines, including those based on DNA, proteins, viral vectors, and virus-like particles as well as a number of combination vaccinations, are in the developmental stage or in preclinical or clinical trials, some of which have shown efficacy in preventing H5N1 infections (13C19). However, such vaccines are not effective enough against divergent strains of H5N1 viruses, CHMFL-ABL-121 thus limiting their ability to produce broad-spectrum protection. As an alternative to vaccines, neutralizing monoclonal antibodies (MAbs) represent a passive therapeutic strategy to provide immediate protection against influenza virus infection. Several effective MAbs against hemagglutinins (HA) of multiple strains of IAVs from group 1 and/or group 2 have been explored, showing broad-spectrum neutralization of the CHMFL-ABL-121 viruses. It was reported previously that MAbs F10 and CR6261 were effective against all tested group 1 IAVs (20, 21), while MAb CR8020 contains broad neutralizing activity against most group 2 viruses, including H3N2 and H7N7 viruses (22). Other reports indicated that MAb F16 was able to recognize the HAs of all 16 subtypes and neutralize both group 1 and 2 IAVs (23). Thus, these identified MAbs may be used as effective passive immunotherapeutics against a broad range of IAVs during influenza pandemics or epidemics because of their ability to target a variety of IAVs in addition to H5N1 virus. However, in the.
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