Vaccine, peptide

An alternative approach to the production of subunit vaccines entails their direct chemical synthesis. Peptides identical in sequence to short stretches of pathogen-derived polypeptide antigens can be easily and economically synthesized. The feasibility of this approach was first verified in the 1960s, when a hexapeptide purified from the enzymatic digest of tobacco mosaic virus was found to confer limited immunological protection against subsequent administration of the intact virus. (The hexapeptide hapten was initially coupled to bovine serum albumin, used as a carrier to ensure an immunological response.) 

Similar synthetic vaccines have also been constructed that confer immunological protection against bacterial toxins, including diphtheria and cholera toxins. Although coupling to a carrier is 

arge scale (600L) Cell harvesting, followed by 

Sterile filtration and aseptic filling into final product container 

Removal of pathogen gene and incorporation into vector genome 

Vaccine vector now expressing pathogen surface antigen 

Similar synthetic vaccines have also been constructed which confer immunological protection against bacterial toxins, including diphtheria and cholera toxins. While coupling to a carrier is generally required to elicit an immunological response, some carriers are inappropriate due to their ability to elicit a hypersensitive reaction, particularly when repeat injections are undertaken. Such difficulties can be avoided by judicious choice of carrier. Often a carrier normally used for vaccination is itself used, e.g. tetanus toxoid has been used as a carrier for peptides derived from influenza haemagglutinin and Plasmodium falciparum. 

Most vaccine vectors developed to date are viral-based, with poxviruses, picornaviruses and adenoviruses being used most. In general, such recombinant viral vectors elicit both strong humoral and cell-mediated immunity. The immunological response (particularly the cell-mediated response) to subunit vaccines is often less pronounced. 

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Development of a peptide vaccine is derived from the identification of the immunodominant epitope of an antigen (141). A polypeptide based on the amino acid sequence of the epitope can then be synthesized. Preparation of a peptide vaccine has the advantage of allowing for large-scale production of a vaccine at relatively low cost. It also allows for selecting the appropriate T- or B-ceU epitopes to be included in the vaccine, which may be advantageous in some cases. Several vaccines based on peptide approaches, such as SPf66 (95) for malaria and an HIV-1 peptide (142) have been in clinical trials. No peptide vaccines are Hcensed as yet. 

Development of conjugate and peptide vaccines requires the typical organic synthesis process and purification. This is a new area for vaccine technologists. Again, the main concern is to maintain the immunogenicity of the vaccine candidate during the chemical reaction and purification steps. 

In addition to the three types of immunological product that are generally available there are two further types synthetic peptide vaccines and monoclonal antibodies. Both have been extensively investigated but neither has, as yet, a place in conventional prophylaxis or therapeutics. 

El-Kasmi, K. C., Fillon, S., Thiesen, D. M., Hartter, H., Brons, N. H. C. and Muller, C. P. (2000), Neutralization of measles virus wild-type isolates after immunization with a synthetic peptide vaccine which is not recognized by neutralizing passive antibodies , J. Gen. Virol., 81, 729-735. 

Fig. 24. Cyclic peptide vaccine candidate bearing the minimally epitopic D1 branch of the Man9 G1cNAc2 antigen of HIV-1 gpl20 recognized by the protective human antibody 2G12.191...

Yamaguchi S, Tatsumi T, Takehara T et al (2010) EphA2-derived peptide vaccine with amphiphilic poly(gamma-glutamic acid) nanoparticles elicits an anti-tumor effect against mouse liver tumor. Cancer Immunol Immunother 59 759-767... 

Tam, J.P. (1988) Synthetic peptide vaccine design Synthesis and properties of a high-density multiple antigenic peptide system. Proc. Natl. Acad. Sci. USA 85, 5409-5413. 

Morgan, D., Diamond, D. M., Gottschall, P. E. et al. A(3 peptide vaccination prevents memory loss in an animal model of Alzheimer s disease. Nature 408 982-985, 2000. 

Moynihan, J.S. et al., A Novel Microencapsulated Peptide Vaccine against Hepatitis B, Vaccine. 19, 3292, 2001. 

Olive, C., Schulze, K., Sun, H. K., Ebensen, T., Horvath, A., Toth, I., and Guzman, C. A. (2007). Enhanced protection against Streptococcus pyogenes infection by intranasal vaccination with a dual antigen component M protein/Sfbl lipid core peptide vaccine formulation. Vaccine 25, 1789-1797. 

Advances in genomics, molecular biology, and recombinant technology have provided new directions for the discovery, development, and manufacture of vaccines. One of the current approaches is a minimalist strategy to decouple the virulence and immunity functions. The aim is to use only the immunity part to confer protection, so that the vaccine is safe to be administered. The approach can be divided into subunit, vector-based, DNA, and peptide vaccines. 

Peptide Vaccines Peptide vaccines are chemically synthesized and normally consist of 8-24 amino acids. In comparison with protein molecules, peptide vaccines are relatively small. They are also known as peptidomimetic vaccines, as they mimic the epitopes. Complex structures of cyclic components, branched chains, or other configurations can be built into the peptide chain. In this way, they possess conformations similar to the epitopes and can be recognized by immune cells. An in silico vaccine design approach has been used to find potential epitopes. A critical aspect of peptide vaccines is to produce 3D structures similar to the native epitopes of the pathogen. 

Engler OB, et al. A liposomal peptide vaccine inducing CD8(- -) T cells in HLA-A2.1 transgenic mice, which recognise human cells encoding hepatitis C virus (HCV) proteins. Vaccine 2004 23 58. 

Tam IP, Lu YA. Vaccine engineering enhancement of immunogenicity of synthetic peptide vaccine related to hepatitis in chemically defined models consisting of T- and B-cell epitopes. Proc Natl Acad Sci USA 1989 86 9084. 

Rosenberg SA, Yang JC, Schwartzentruber DJ, et al. Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma. Nat Med 1998 4(3) 321-327. 

Strominger, J. (1995). Peptide vaccination against cancer Nature Med. 1(11), 1140. 

Unlike peptide vaccines, which must be specific for each individual s MHC, expression of plasmid-encoded tumor antigens within the host antigen-presenting cells following vaccination results in the presentation of multiple tumor-associated epitopes in the context... 

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