Protective epitope

Rotavirus. Rotavims causes infant diarrhea, a disease which has major socio-economic impact. In developing countries it is the major cause of death in infants worldwide, causing up to 870,000 deaths per year. In the United States, diarrhea is stiU a primary cause of physician visits and hospitalization, although the mortaUty rate is relatively low. Studies have estimated a substantial cost benefit for a vaccination program in the United States (67—69). Two membrane proteins (VP4 and VP7) of the vims have been identified as protective epitopes and most vaccine development programs are based on these two proteins as antigens. Both Hve attenuated vaccines and subunit vaccines are being developed (68). 

Two studies have involved the fusion of an antigen to P-glucuronidase (GUS). Gil et al. [61] fused GUS to the 2L21 protective epitope from canine parvovirus, and Dus Santos et al. [23] fused GUS to the protective epitope from FMDV. Transformants in both cases were selected on the basis of GUS activity, and both proved to be immunogenic. Mice immunized orally or parenterally with the GUS-FMDV epitope fusion were completely protected against challenge with the native virus. 

Precise definition of the host-protection epitope(s) of the Taenia and Echinococcus vaccine antigens would be valuable if it were to lead to the development of a synthetic vaccine or provide reagents to assist with quality control of vaccine production. Identification of a limited number of host-protective fragments may allow the recombinant antigen to be replaced by synthetic peptides. This would have significant advantages in the production... 

The most advanced of all the malaria, vaccine candidates is SPf66 (94,95). It is a synthetic polypeptide. The peptide represents several protective epitopes correlated to several proteins of the pre-erythrocytic and asexual blood stage of Plasmodianfalciporum. Extensive clinical trials with this vaccine have been carried out in South America and Africa (95—97). The efficacy of the vaccine varied in different regions, and generally lower than expected in a developed country. Consequently, the general application of the vaccine still generates much debate (98). However, this vaccine represents a major advance in the development of a malaria vaccine. 

Polysaccharides are ideally located on the surface of bacteria and are a source of the most highly conserved protective epitopes. One of the challenges in vaccine development during the final quarter of the 20th century was to develop a better anti-carbohydrate immune response for CPS and LPS. Conjugation of polysaccharides to proteins provided a solution to some of the limitations found for natural compounds. 

Humanized Antibodies. For human immunotherapeutic applications, the optimal antibody should be of human origin. Immune libraries are perhaps the best way to produce neutralizing antibody responses to protective epitopes on infectious pathogens [26]. For therapeutic purposes, the efficacy of nonhuman-derived monoclonal antibodies is limited by the induction of anti-mouse immune response. Using hybridoma methods to immortalize human B-cells for the construction of human monoclonal antibodies would avoid these issues. However, the absence of a suitable fusion partner and other technical issues has made methods that rely on human B-cell immortalization problematic, forcing reliance on nonhuman organisms [6]. 

Mathews JH, Roehrig JT. Determination of the protective epitopes on the glycoproteins of Venezuelan equine encephalomyelitis virus by passive transfer of monoclonal antibodies. J Immunol. 1982 129(6) 2763—2767. 

Malito, E., Faleri, A., Lo Surdo, R, et al. (2013) Defining a Protective Epitope on Eactor H Binding Protein, a Key Meningococcal Virulence Factor and Vaccine Antigen. Proceedings of the National Academy of Sciences of the United States of America, 110 (9), 3304-3309. 

However, a degree of uncertainty concerning the minimal protective epitope in human and particularly in infants was recognized. ... 

In a different approaeh, the p-D-glucan was selected as a target molecule as it has been shown to contain one or more protective epitopes... 

The synthesis of these molecules is complex due to the incompatibility of uronic acid protective groups with the preservation of acetyl group at specific positions in the final oligosaccharide. A synthetic hepta-saccharide-HSA conjugate elicits high-titre IgG responses in mice but antibodies are non-protective. At present the only alternative is the search for larger oligosaccharides, in hope for the presence of a protective epitope. 

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