Antibody-mediated neutralization

The results from a number of structural studies on several different families of viruses have begun to converge into a unified view of the mechanism of antibody-mediated neutralization of viruses. Previously, the literature was rife with conflicting results and hypotheses. This was most likely due to the inherent difficulty in trying to quantify binding constants... 

Over the past few decades several mechanisms of antibody-mediated neutralization have been proposed. 

The following studies were important because they represented the first time that cryo-EM studies (Fig. 1) could be interpreted with atomic structures of all of the components and this modeling was subsequently validated by the crystal structure of the Fab-virus complex. Further, these studies were able to directly test the prevailing hypotheses concerning the mechanism of antibody-mediated neutralization and viral escape of... 

Papillomavirus infections usually cause benign epithelial papillomas, but a subset of human papillomaviruses is associated with cervical cancer [137]. More than 90% of cervical cancers are associated with sexually transmitted genital human papillomavirus. Because of this high degree of association and the high mortality rate of cervical cancer, it is of great importance to understand the mechanism of antibody-mediated neutralization to facilitate vaccine development. 

After reviewing most of the more recent structural studies on antibody-mediated neutralization of viruses, it is important to briefly note potential problems with the assays used to characterize the antibodies. 

These studies have all shown the importance of hybrid technology. Antibodies have been used to elucidate the architecture of viruses and to identify receptor-binding regions. They have directly addressed the mechanism of antibody-mediated neutralization, which has greatly impacted the development of vaccines. Finally, they have improved our understanding about the forces that have driven the evolution of viral structure. It is likely that such studies will continue to help us understand the architecture of macro-macromolecular complexes and the dynamics of these viral capsids. 

Montefiori, D. C., Collman, R. G., Zhou, T. R. F. J. Y., Bilska, M., Hoxie, J. A., Moore, J. P., and Bolognesi, D. P. (1998) Evidence that antibody-mediated neutralization of human immunodeficiency virus type 1 by sera from infected individuals is independent of coreceptor usage. J. Virol. 72,1886-1893. 

Two types of immunity may be induced in response to an antigen, namely humoral immunity mediated by antigen-specific antibodies produced by B lymphocytes, and cell-mediated immunity produced by activated macrophages and cytotoxic T lymphocytes. Antibodies may neutralize pathogens, whereas... 

Brioen, P., Dekegel, D., and Boeye, A. (1983). Neutralization of poliovirus by antibody-mediated polymerization. Virology 127, 463-468. 

Antibody-Mediated Immunity (Humoral Immunity) This is the production of antibodies by B lymphocytes to neutralize and destroy an antigen. Antibodies are created in response to sufficient exposure to the antigen through an invasion by the antigen or a vaccination. A vaccination contains small amounts of the antigen sufficient to trigger the immune system to create antibodies. 

After 1998 there was a significant increase in the number of cases of pure red cell aplasia (PRCA) associated with subcutaneous injections of rHuEPO in the renal dialysis population. PRCA is a relatively rare condition. It presents as a sudden onset of severe isolated anemia characterized by near-complete absence of erythroid precursors in the bone marrow [2]. Most of the initial reports in the literature before 1998 involved isolated cases, of which 50% had no known cause. After 1998, the PRCA was shown to be related to neutralizing antibodies to erythropoietin that cross-reacted with endogenous EPO [3]. Most of these reported antibody-mediated cases were for patients using Eprex (Ortho Biotech, a division of Janssen-Cilag, Bridgewater, NJ). In total between January 1,1989 and June 30, 2004, the company reported a total of 206 cases, of which 155 occurred in the peak years of 2001-2003 [4]. The mean time from initial exposure to onset of PRCA was 9.1 months [5]. 

---